Human spinal cord injury: motor unit properties and behaviour.

PubMed

Thomas, C K; Bakels, R; Klein, C S; Zijdewind, I

2014-01-01

Spinal cord injury (SCI) results in widespread variation in muscle function. Review of motor unit data shows that changes in the amount and balance of excitatory and inhibitory inputs after SCI alter management of motoneurons. Not only are units recruited up to higher than usual relative forces when SCI leaves few units under voluntary control, the force contribution from recruitment increases due to elevation of twitch/tetanic force ratios. Force gradation and precision are also coarser with reduced unit numbers. Maximal unit firing rates are low in hand muscles, limiting voluntary strength, but are low, normal or high in limb muscles. Unit firing rates during spasms can exceed voluntary rates, emphasizing that deficits in descending drive limit force production. SCI also changes muscle properties. Motor unit weakness and fatigability seem universal across muscles and species, increasing the muscle weakness that arises from paralysis of units, motoneuron death and sensory impairment. Motor axon conduction velocity decreases after human SCI. Muscle contractile speed is also reduced, which lowers the stimulation frequencies needed to grade force when paralysed muscles are activated with patterned electrical stimulation. This slowing does not necessarily occur in hind limb muscles after cord transection in cats and rats. The nature, duration and level of SCI underlie some of these species differences, as do variations in muscle function, daily usage, tract control and fibre-type composition. Exploring this diversity is important to promote recovery of the hand, bowel, bladder and locomotor function most wanted by people with SCI. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Survey of spinal cord injury-induced neurogenic bladder studies using the Web of Science.

PubMed

Zou, Benjing; Zhang, Yongli; Li, Yucheng; Wang, Zantao; Zhang, Ping; Zhang, Xiyin; Wang, Bingdong; Long, Zhixin; Wang, Feng; Song, Guo; Wang, Yan

2012-08-15

To identify global trends in research on spinal cord injury-induced neurogenic bladder, through a bibliometric analysis using the Web of Science. We performed a bibliometric analysis of studies on spinal cord injury-induced neurogenic bladder using the Web of Science. Data retrieval was performed using key words "spinal cord injury", "spinal injury", "neurogenic bladder", "neuropathic bladder", "neurogenic lower urinary tract dysfunction", "neurogenic voiding dysfunction", "neurogenic urination disorder" and "neurogenic vesicourethral dysfunction". (a) published peer-reviewed articles on spinal cord injury-induced neurogenic bladder indexed in the Web of Science; (b) type of articles: original research articles and reviews; (c) year of publication: no limitation. (a) articles that required manual searching or telephone access; (b) Corrected papers and book chapters. (1) Annual publication output; (2) distribution according to journals; (3) distribution according to subject areas; (4) distribution according to country; (5) distribution according to institution; and (6) top cited publications. There were 646 research articles addressing spinal cord injury-induced neurogenic bladder in the Web of Science. Research on spinal cord injury-induced neurogenic bladder was found in the Science Citation Index-Expanded as of 1946. The United States, Ireland and Switzerland were the three major countries contributing to studies in spinal cord injury-induced neurogenic bladder in the 1970s. However, in the 1990s, the United States, the United Kingdom, the Netherlands, Germany and Japan published more papers on spinal cord injury-induced neurogenic bladder than Switzerland, and Ireland fell off the top ten countries list. In this century, the United States ranks first in spinal cord injury-induced neurogenic bladder studies, followed by France, the United Kingdom, Germany, Switzerland and Japan. Subject categories including urology, nephrology and clinical neurology, as well as rehabilitation, are represented in spinal cord injury-induced neurogenic bladder studies. From our analysis of the literature and research trends, we conclude that spinal cord injury-induced neurogenic bladder is a hot topic that will continue to generate considerable research interest in the future.

Spinal cord injuries among paragliders in Norway.

PubMed

Rekand, T; Schaanning, E E; Varga, V; Schattel, U; Gronning, M

2008-06-01

A national retrospective descriptive study. To study the clinical effects of spinal cord injuries (SCIs) caused by paragliding accidents in Norway. Spinal cord units at Haukeland University Hospital, Sunnaas Rehabilitation Hospital and St Olav Hospital in Norway. We studied the medical files for nine patients with SCI caused by paragliding accidents to evaluate the circumstances of the accidents, and clinical effects of injury. We obtained the data from hospital patient files at all three spinal units in Norway and crosschecked them through the Norwegian Paragliding Association's voluntary registry for injuries. All patients were hospitalized from 1997 to 2006, eight men and one woman, with mean age 30.7 years. The causes of the accidents were landing problems combined with unexpected wind whirls, technical problems and limited experience with unexpected events. All patients contracted fractures in the thoracolumbal junction of the spine, most commonly at the L1 level. At clinical follow-up, all patients presented clinically incomplete SCI (American Spinal Injury Association impairment scores B-D). Their main health problems differed widely, ranging from urinary and sexual disturbances to neuropathic pain and loss of motor functioning. Only three patients returned to full-time employment after rehabilitation. Paragliding accidents cause spinal fractures predominantly in the thoracolumbal junction with subsequent SCIs and increased morbidity. All patients experienced permanent health problems that influenced daily activities and required long-time clinical follow-up and medical intervention. Better education in landing techniques and understanding of aerodynamics may reduce the risk of paragliding accidents.

A systematic review of definitions and classification systems of adjacent segment pathology.

PubMed

Kraemer, Paul; Fehlings, Michael G; Hashimoto, Robin; Lee, Michael J; Anderson, Paul A; Chapman, Jens R; Raich, Annie; Norvell, Daniel C

2012-10-15

Systematic review. To undertake a systematic review to determine how "adjacent segment degeneration," "adjacent segment disease," or clinical pathological processes that serve as surrogates for adjacent segment pathology are classified and defined in the peer-reviewed literature. Adjacent segment degeneration and adjacent segment disease are terms referring to degenerative changes known to occur after reconstructive spine surgery, most commonly at an immediately adjacent functional spinal unit. These can include disc degeneration, instability, spinal stenosis, facet degeneration, and deformity. The true incidence and clinical impact of degenerative changes at the adjacent segment is unclear because there is lack of a universally accepted classification system that rigorously addresses clinical and radiological issues. A systematic review of the English language literature was undertaken and articles were classified using the Grades of Recommendation Assessment, Development, and Evaluation criteria. RESULTS.: Seven classification systems of spinal degeneration, including degeneration at the adjacent segment, were identified. None have been evaluated for reliability or validity specific to patients with degeneration at the adjacent segment. The ways in which terms related to adjacent segment "degeneration" or "disease" are defined in the peer-reviewed literature are highly variable. On the basis of the systematic review presented in this article, no formal classification system for either cervical or thoracolumbar adjacent segment disorders currently exists. No recommendations regarding the use of current classification of degeneration at any segments can be made based on the available literature. A new comprehensive definition for adjacent segment pathology (ASP, the now preferred terminology) has been proposed in this Focus Issue, which reflects the diverse pathology observed at functional spinal units adjacent to previous spinal reconstruction and balances detailed stratification with clinical utility. A comprehensive classification system is being developed through expert opinion and will require validation as well as peer review. Strength of Statement: Strong.

Effect of Facetectomy on the Three-Dimensional Biomechanical Properties of the Fourth Canine Cervical Functional Spinal Unit: A Cadaveric Study.

PubMed

Bösch, Nadja; Hofstetter, Martin; Bürki, Alexander; Vidondo, Beatriz; Davies, Fenella; Forterre, Franck

2017-11-01

Objective  To study the biomechanical effect of facetectomy in 10 large breed dogs (>24 kg body weight) on the fourth canine cervical functional spinal unit. Methods  Canine cervical spines were freed from all muscles. Spines were mounted on a six-degrees-of-freedom spine testing machine for three-dimensional motion analysis. Data were recorded with an optoelectronic motion analysis system. The range of motion was determined in all three primary motions as well as range of motion of coupled motions on the intact specimen, after unilateral and after bilateral facetectomy. Repeated-measures analysis of variance models were used to assess the changes of the biomechanical properties in the three treatment groups considered. Results  Facetectomy increased range of motion of primary motions in all directions. Axial rotation was significantly influenced by facetectomy. Coupled motion was not influenced by facetectomy except for lateral bending with coupled motion axial rotation. The coupling factor (coupled motion/primary motion) decreased after facetectomy. Symmetry of motion was influenced by facetectomy in flexion-extension and axial rotation, but not in lateral bending. Clinical Significance  Facet joints play a significant role in the stability of the cervical spine and act to maintain spatial integrity. Therefore, cervical spinal treatments requiring a facetectomy should be carefully planned and if an excessive increase in range of motion is expected, complications should be anticipated and reduced via spinal stabilization. Schattauer GmbH Stuttgart.

A technical report on video-assisted thoracoscopy in thoracic spinal surgery. Preliminary description.

PubMed

Regan, J J; Mack, M J; Picetti, G D

1995-04-01

This report is a preliminary description of the efficacy of video-assisted thoracoscopic surgery in thoracic spinal procedures that otherwise require open thoracotomy. This report sought to describe the efficacy of video-assisted thoracoscopic surgery in thoracic spinal procedures that otherwise require open thoracotomy. In a landmark study that compared video-assisted thoracoscopic surgery for peripheral lung lesions with thoracotomy, video-assisted thoracoscopic surgery reduced postoperative pain, improved early shoulder girdle function, and shortened hospital stay. Video-assisted thoracoscopic surgery was performed in 12 thoracic spinal patients (herniated nucleus pulposus, infection, tumor, or spinal deformity) and is described in detail in this report. Video-assisted thoracoscopic surgery in thoracic spinal surgery resulted in little postoperative pain, short intensive care unit and hospital stays, and little or no morbidity. In the short follow-up period, there was no post-thoracotomy pain syndrome nor neurologic sequelae in these patients. Operative time decreased dramatically as experience was gained with the procedure. Given consistently improving surgical skills, a number of thoracic spinal procedures using video-assisted thoracoscopic surgery, including thoracic discectomy, internal rib thoracoplasty, anterior osteotomy, corpectomy, and fusion, can be performed safely with no additional surgical time or risk to the patient.

Co-induction of the heat shock response ameliorates disease progression in a mouse model of human spinal and bulbar muscular atrophy: implications for therapy

PubMed Central

Malik, Bilal; Nirmalananthan, Niranjanan; Gray, Anna L.; La Spada, Albert R.; Hanna, Michael G.

2013-01-01

Spinal and bulbar muscular atrophy, also known as Kennedy’s disease, is an adult-onset hereditary neurodegenerative disorder caused by an expansion of the polyglutamine repeat in the first exon in the androgen receptor gene. Pathologically, the disease is defined by selective loss of spinal and bulbar motor neurons causing bulbar, facial and limb weakness. Although the precise disease pathophysiology is largely unknown, it appears to be related to abnormal accumulation of the pathogenic androgen receptor protein within the nucleus, leading to disruption of cellular processes. Using a mouse model of spinal and bulbar muscular atrophy that exhibits many of the characteristic features of the human disease, in vivo physiological assessment of muscle function revealed that mice with the pathogenic expansion of the androgen receptor develop a motor deficit characterized by a reduction in muscle force, abnormal muscle contractile characteristics, loss of functional motor units and motor neuron degeneration. We have previously shown that treatment with arimoclomol, a co-inducer of the heat shock stress response, delays disease progression in the mutant superoxide dismutase 1 mouse model of amyotrophic lateral sclerosis, a fatal motor neuron disease. We therefore evaluated the therapeutic potential of arimoclomol in mice with spinal and bulbar muscular atrophy. Arimoclomol was administered orally, in drinking water, from symptom onset and the effects established at 18 months of age, a late stage of disease. Arimoclomol significantly improved hindlimb muscle force and contractile characteristics, rescued motor units and, importantly, improved motor neuron survival and upregulated the expression of the vascular endothelial growth factor which possess neurotrophic activity. These results provide evidence that upregulation of the heat shock response by treatment with arimoclomol may have therapeutic potential in the treatment of spinal and bulbar muscular atrophy and may also be a possible approach for the treatment of other neurodegenerative diseases. PMID:23393146

Plasticity in reflex pathways to the lower urinary tract following spinal cord injury

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2013-01-01

The lower urinary tract has two main functions, storage and periodic expulsion of urine, that are regulated by a complex neural control system in the brain and lumbosacral spinal cord. This neural system coordinates the activity of two functional units in the lower urinary tract: (1) a reservoir (the urinary bladder) and (2) an outlet (consisting of bladder neck, urethra and striated muscles of the external urethra sphincter). During urine storage the outlet is closed and the bladder is quiescent to maintain a low intravesical pressure. During micturition the outlet relaxes and the bladder contracts to promote efficient release of urine. This reciprocal relationship between bladder and outlet is generated by reflex circuits some of which are under voluntary control. Experimental studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through a coordination center (the pontine micturition center) located in the rostral brainstem. This reflex pathway is in turn modulated by higher centers in the cerebral cortex that are involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary control of voiding as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. However the bladder does not empty efficiently because coordination between the bladder and urethral outlet is lost. Studies in animals indicate that dysfunction of the lower urinary tract after spinal cord injury is dependent in part on plasticity of bladder afferent pathways as well as reorganization of synaptic connections in the spinal cord. Reflex plasticity is associated with changes in the properties of ion channels and electrical excitability of afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and/or the peripheral target organs. PMID:21596038

[Acute-stage para- and tetraplegia].

PubMed

Hachen, H J

1993-03-20

A quarter of a century ago, in October 1964, the first spinal cord injury center in Switzerland was opened at Geneva University Hospital. At that time all para- and tetraplegics were classified as "high-risk" patients. Early mortality, covering the initial four weeks following trauma, was still around 15%. The available resources for diagnostic assessment were limited to clinical examination and neuroradiological assessment (subsequently improved by the introduction of tomography and gas myelography). A great many patients suffered a deteriorated neurological level due to inadequate, multiple transfers between hospitals. Most patients who are paralyzed following a road-traffic accident show severe polytrauma. Their chances of survival and functional recovery have greatly improved in recent years due to efficient emergency transport by helicopter, admission to an intensive care unit (respiratory therapy, prophylactic anticoagulation, gastrointestinal cytoprotection, prevention of pressure sores, etc.) and a comprehensive medico-surgical team approach (orthopedic surgeons, neurosurgeons, ICU specialists, internists, etc.). Evaluation of the spine and spinal cord by NMR and CT scan allows precise assessment of the extent of CNS damage and provides additional guide-lines regarding efficient surgical reposition and spinal fusion. Ongoing experimental research in neurophysiology and neurobiochemistry of the brain and spinal cord is presently yielding some interesting results which hold out new hopes for functional recovery in some specific types of incomplete spinal cord trauma.

Men's adjustment to spinal cord injury: the unique contributions of conformity to masculine gender norms.

PubMed

Burns, Shaun Michael; Hough, Sigmund; Boyd, Briana L; Hill, Justin

2010-06-01

Men constitute 82% of the approximately 250,000 people in the United States living with a spinal cord injury. Unfortunately, however, little is known about the impact of men's adherence to gender norms on their adjustment to such injuries. The present investigation examined the utility of masculine norms in explaining variance in depression beyond that accounted for by commonly identified predictors of men's adjustment following spinal cord injury. As hypothesized, results suggested that men's adherence to masculine norms accounted for unique variance in their depression scores beyond that contributed by social support, environmental barriers/access, and erectile functioning. Respondents who adhered to norms stressing the primacy of men's work demonstrated lower rates of depression, whereas those who conformed to norms for self-reliance demonstrated higher depression scores. The authors discuss future research directions and potential psychotherapeutic strategies for working with men with spinal cord injuries.

Measurement properties of the Spinal Cord Injury-Functional Index (SCI-FI) short forms.

PubMed

Heinemann, Allen W; Dijkers, Marcel P; Ni, Pengsheng; Tulsky, David S; Jette, Alan

2014-07-01

To evaluate the psychometric properties of the Spinal Cord Injury-Functional Index (SCI-FI) short forms (basic mobility, self-care, fine motor, ambulation, manual wheelchair, and power wheelchair) based on internal consistency; correlations between short forms banks, full item bank forms, and a 10-item computer adaptive test version; magnitude of ceiling and floor effects; and test information functions. Cross-sectional cohort study. Six rehabilitation hospitals in the United States. Individuals with traumatic spinal cord injury (N=855) recruited from 6 national Spinal Cord Injury Model Systems facilities. Not applicable. SCI-FI full item bank, 10-item computer adaptive test, and parallel short form scores. The SCI-FI short forms (with separate versions for individuals with paraplegia and tetraplegia) demonstrate very good internal consistency, group-level reliability, excellent correlations between short forms and scores based on the total item bank, and minimal ceiling and floor effects (except ceiling effects for persons with paraplegia on self-care, fine motor, and power wheelchair ability and floor effects for persons with tetraplegia on self-care, fine motor, and manual wheelchair ability). The test information functions are acceptable across the range of scores where most persons in the sample performed. Clinicians and researchers should consider the SCI-FI short forms when computer adaptive testing is not feasible. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Using Truncated Lectures, Conceptual Exercises, and Manipulatives to Improve Learning in the Neuroanatomy Classroom

ERIC Educational Resources Information Center

Krontiris-Litowitz, Johanna

2008-01-01

Functional Neuroanatomy is a course designed to help students learn the function and anatomy of the human nervous system. Historically, students have had difficulty with the spinal tract curricular unit and frequently resorted to memorization to "learn" the material. They performed poorly on exams and failed to demonstrate competence in the…

Association of insurance status and spinal fusion usage in the United States during two decades.

PubMed

John, Jason; Mirahmadizadeh, Alireza; Seifi, Ali

2018-05-01

This study examined the distribution of spinal fusion usage among payer groups in the United States. Using the National Inpatient Sample (NIS) database, total discharges, length of stay, and mean hospital charges of patients who underwent spinal fusion from 1997 to 2014 in the United States were determined and analyzed. 5,715,625 total discharges with spinal fusion were reported. Among them, 2,875,188 (50.3%) were covered by private insurance, 1,710,182 by Medicare (29.9%), 342,638 (6.0%) by Medicaid, and 91,990 (1.6%) were uninsured. A statistically significant increase in spinal fusion usage occurred within each payer group over the study period (P < 0.001). For every year of the study period, private insurance patients had the most number and uninsured patients had the least number of total discharges with spinal fusion. Furthermore, annual growth in spinal fusion usage was greatest among private insurance patients, and smallest among uninsured patients. Total discharges with spinal fusion increased significantly across all payer groups between 1997 and 2014, but not equally. Further inquiry is indicated to determine the etiology of spinal fusion usage discrepancies between payer groups. Copyright © 2018 Elsevier Ltd. All rights reserved.

Constitutively active 5-HT2/α1 receptors facilitate muscle spasms after human spinal cord injury

PubMed Central

D'Amico, Jessica M.; Murray, Katherine C.; Li, Yaqing; Chan, K. Ming; Finlay, Mark G.; Bennett, David J.

2013-01-01

In animals, the recovery of motoneuron excitability in the months following a complete spinal cord injury is mediated, in part, by increases in constitutive serotonin (5-HT2) and norepinephrine (α1) receptor activity, which facilitates the reactivation of calcium-mediated persistent inward currents (CaPICs) without the ligands serotonin and norepinephrine below the injury. In this study we sought evidence for a similar role of constitutive monoamine receptor activity in the development of spasticity in human spinal cord injury. In chronically injured participants with partially preserved sensory and motor function, the serotonin reuptake inhibitor citalopram facilitated long-lasting reflex responses (spasms) previously shown to be mediated by CaPICs, suggesting that in incomplete spinal cord injury, functional descending sources of monoamines are present to activate monoamine receptors below the lesion. However, in participants with motor or motor/sensory complete injuries, the inverse agonist cyproheptadine, which blocks both ligand and constitutive 5-HT2/α1 receptor activity, decreased long-lasting reflexes, whereas the neutral antagonist chlorpromazine, which only blocks ligand activation of these receptors, had no effect. When tested in noninjured control participants having functional descending sources of monoamines, chlorpromazine was effective in reducing CaPIC-mediated motor unit activity. On the basis of these combined results, it appears that in severe spinal cord injury, facilitation of persistent inward currents and muscle spasms is mainly mediated by the activation of constitutive 5-HT2 and α1 receptor activity. Drugs that more selectively block these constitutively active monoamine receptors may provide better oral control of spasticity, especially in motor complete spinal cord injury where reducing motoneuron excitability is the primary goal. PMID:23221402

Patient perceptions of environmental control units: experiences of Veterans with spinal cord injuries and disorders receiving inpatient VA healthcare.

PubMed

Etingen, Bella; Martinez, Rachael N; Vallette, Marissa A; Dendinger, Ryan; Bidassie, Balmatee; Miskevics, Scott; Khan, Hira T; Cozart, Huberta T; Locatelli, Sara M; Weaver, Frances M

2018-05-01

To assess patients' perceptions of environmental control units (ECUs) at Veterans Affairs Spinal Cord Injury Centers. A brief questionnaire was conducted with patients in real-time while they were hospitalised ("on-the-spot questionnaire"); a survey was mailed to patients who had recently been discharged from a hospital stay ("discharge survey"). Data were analysed using descriptive statistics. Seventy on-the-spot questionnaires and 80 discharge surveys were collected. ECU features used most frequently were comparable in responses from both surveys: watching TV/movies (81%, 85%), calling the nurse (68%, 61%), turning lights on/off (63%, 52%), adjusting the bed (53%, 33%), and playing games (39%, 24%). Many on-the-spot questionnaire respondents felt the ECU met their need for independence a great deal (42%). Most respondents to both surveys were satisfied with the ECU (71%, 57%). Areas for improvement included user training, improved functionality of the device and its features, and device design. ECUs were well-accepted by persons with spinal cord injuries/disorders (SCI/D) in the inpatient setting, and increased patients' perceptions of independence. To maximise usability and satisfaction, facilities should ensure that comprehensive training on ECU use and features available is offered to all patients, and resources are available for timely troubleshooting and maintenance. Implications for rehabilitation An environmental control unit (ECU) is a form of assistive technology that allows individuals with disabilities (such as spinal cord injuries and disorders [SCI/D]) to control functional and entertainment-related aspects of their environment. ECU use can increase functioning, independence and psychosocial well-being among individuals with SCI/D, by allowing users to reclaim control over day-to-day activities that are otherwise limited by their disability. Our study results indicate that, among persons with SCI/D, ECUs are well-accepted and increase perceptions of independence. To maximise usability and patient satisfaction, facilities should ensure that comprehensive training on how to use ECUs and what features are available is offered to all patients, and resources are available for timely troubleshooting and maintenance.

Age at spinal cord injury determines muscle strength

PubMed Central

Thomas, Christine K.; Grumbles, Robert M.

2014-01-01

As individuals with spinal cord injury (SCI) age they report noticeable deficits in muscle strength, endurance and functional capacity when performing everyday tasks. These changes begin at ~45 years. Here we present a cross-sectional analysis of paralyzed thenar muscle and motor unit contractile properties in two datasets obtained from different subjects who sustained a cervical SCI at different ages (≤46 years) in relation to data from uninjured age-matched individuals. First, completely paralyzed thenar muscles were weaker when C6 SCI occurred at an older age. Muscles were also significantly weaker if the injury was closer to the thenar motor pools (C6 vs. C4). More muscles were strong (>50% uninjured) in those injured at a younger (≤25 years) vs. young age (>25 years), irrespective of SCI level. There was a reduction in motor unit numbers in all muscles tested. In each C6 SCI, only ~30 units survived vs. 144 units in uninjured subjects. Since intact axons only sprout 4–6 fold, the limits for muscle reinnervation have largely been met in these young individuals. Thus, any further reduction in motor unit numbers with time after these injuries will likely result in chronic denervation, and may explain the late-onset muscle weakness routinely described by people with SCI. In a second dataset, paralyzed thenar motor units were more fatigable than uninjured units. This gap widened with age and will reduce functional reserve. Force declines were not due to electromyographic decrements in either group so the site of failure was beyond excitation of the muscle membrane. Together, these results suggest that age at SCI is an important determinant of long-term muscle strength, and fatigability, both of which influence functional capacity. PMID:24478643

Intensive exercise program after spinal cord injury ("Full-On"): study protocol for a randomized controlled trial.

PubMed

Galea, Mary P; Dunlop, Sarah A; Davis, Glen M; Nunn, Andrew; Geraghty, Timothy; Hsueh, Ya-seng Arthur; Churilov, Leonid

2013-09-11

Rehabilitation after spinal cord injury (SCI) has traditionally involved teaching compensatory strategies for identified impairments and deficits in order to improve functional independence. There is some evidence that regular and intensive activity-based therapies, directed at activation of the paralyzed extremities, promotes neurological improvement. The aim of this study is to compare the effects of a 12-week intensive activity-based therapy program for the whole body with a program of upper body exercise. A multicenter, parallel group, assessor-blinded randomized controlled trial will be conducted. One hundred eighty-eight participants with spinal cord injury, who have completed their primary rehabilitation at least 6 months prior, will be recruited from five SCI units in Australia and New Zealand. Participants will be randomized to an experimental or control group. Experimental participants will receive a 12-week program of intensive exercise for the whole body, including locomotor training, trunk exercises and functional electrical stimulation-assisted cycling. Control participants will receive a 12-week intensive upper body exercise program. The primary outcome is the American Spinal Injuries Association (ASIA) Motor Score. Secondary outcomes include measurements of sensation, function, pain, psychological measures, quality of life and cost effectiveness. All outcomes will be measured at baseline, 12 weeks, 6 months and 12 months by blinded assessors. Recruitment commenced in January 2011. The results of this trial will determine the effectiveness of a 12-week program of intensive exercise for the whole body in improving neurological recovery after spinal cord injury. NCT01236976 (10 November 2010), ACTRN12610000498099 (17 June 2010).

Progressive Paraplegia from Spinal Cord Stimulator Lead Fibrotic Encapsulation: A Case Report.

PubMed

Benfield, Jon; Maknojia, Asif; Epstein, Franklin

2016-03-01

Ten years after placement of a spinal cord stimulator (SCS) and resolution of pain, this patient presented with progressive paraplegia, worsening thoracic radicular pain at the same dermatome level of the electrodes, and bowel and bladder incontinence. Computed tomographic myelogram confirmed thoracic spinal cord central canal stenosis at the level of electrodes. After removal of the fibrotic tissue and electrodes, the patient had resolution of his thoracic radicular pain and a return of his pre-SCS pain and minimal neurologic and functional return. To the authors' knowledge, no studies have been identified with thoracic SCS lead fibrosis in the United States causing permanent paraplegia. Only one other case has been reported in Madrid, Spain. Patients with SCS presenting with loss of pain relief, new-onset radicular or neuropathic pain in same dermatome(s) as SCS electrodes, worsening neuromuscular examination, or new bladder or bowel incontinence need to be evaluated for complications regarding SCS implantation causing spinal stenosis and subsequent cord compression to avoid permanent neurologic deficits.

Functional relationship between brainstem putative pain-facilitating neurons and spinal nociceptfive neurons during development of inflammation in rats.

PubMed

Salas, Rafael; Ramirez, Karla; Tortorici, Victor; Vanegas, Horacio; Vazquez, Enrique

2018-05-01

The so-called on- and off-cells of the rostral ventromedial medulla (RVM) send their axons to the spinal dorsal horn. Activation of on-cells precedes and coincides with a facilitation, and activation of off-cells coincides with an inhibition, of withdrawal reflexes elicited by noxious agents. Considerable evidence supports the notion that on- and off-cells modulate nocifensive reflexes during opioid and non-opioid action and also during normal circumstances and during peripheral neuropathy and inflammation. Yet it is unclear whether on- and off-cells act upon sensory spinal circuits that might lead to ascending projections and the experience of pain. Here, in deeply anesthetized rats we recorded single unit discharges from pairs of one on-like or off-like cell in RVM and a nociceptive neuron in the spinal dorsal horn with input from a hind paw. Both ongoing activity and responses to a calibrated noxious stimulus applied to the paw were documented during basal conditions and during development of paw inflammation. Probably due to the strong barbiturate anesthesia, off-like cells were depressed and did not yield interpretable results. However, we showed for the first time that during the increase in neuronal activity that results from paw inflammation the activity of spinal nociceptive neurons reflects the activity of their partner on-like cells in a highly correlated manner. This implies a tight relationship between spinal sensory and RVM modulatory functions that may underlie inflammation-induced hyperreflexia and clinically relevant hyperalgesia. Copyright © 2018 Elsevier B.V. All rights reserved.

U.S. Veterans Hospital, Jefferson Barracks, Spinal Cord Injury Unit and ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

U.S. Veterans Hospital, Jefferson Barracks, Spinal Cord Injury Unit and Tuberculosis Neuropsychiatric Building, VA Medical Center, Jefferson Barracks Division 1 Jefferson Barracks Drive, Saint Louis, Independent City, MO

Spinal injuries in New Zealand rugby and rugby league--a twenty year survey.

PubMed

Armour, K S; Clatworthy, B J; Bean, A R; Wells, J E; Clarke, A M

1997-12-12

To establish trends in frequency of serious spinal cord injuries in rugby and rugby league over a 20 year period and to elucidate patterns of injury from retrospective analysis of cases admitted to New Zealand's two spinal injuries units. A detailed survey of unit records with follow-up of selected patients; statistical analysis of data. During the 20 years 1976 to 1995, 119 rugby and 22 rugby league players (total 141) were admitted to New Zealand's two spinal injuries units suffering serious spinal injuries and 47 of these became permanently confined to wheelchairs. There was a steady increase in frequency throughout the period studied. Of the injuries 83% occurred in forwards and 17% in backs. In rugby it was the scrum which produced most injuries, and in rugby league it was the tackle. The early season month of April produced most spinal injuries. In the eighteen months since intense compulsory educational programmes on safety were introduced by the New Zealand Rugby Union there have been no serious spinal cord injuries from rugby scrums. Contrary to widespread belief, there has not been a decrease in spinal cord injuries in rugby following rule changes in the mid 1980s. The information produced by this retrospective study has been an effective educational platform to make rugby and rugby league safer.

Consumer preference in ranking walking function utilizing the walking index for spinal cord injury II.

PubMed

Patrick, M; Ditunno, P; Ditunno, J F; Marino, R J; Scivoletto, G; Lam, T; Loffree, J; Tamburella, F; Leiby, B

2011-12-01

Blinded rank ordering. To determine consumer preference in walking function utilizing the walking Index for spinal cord injury II (WISCI II) in individuals with spinal cord injury (SCI)from the Canada, the Italy and the United States of America. In all, 42 consumers with incomplete SCI (25 cervical, 12 thoracic, 5 lumbar) from Canada (12/42), Italy (14/42) and the United States of America (16/42) ranked the 20 levels of the WISCI II scale by their individual preference for walking. Subjects were blinded to the original ranking of the WISCI II scale by clinical scientists. Photographs of each WISCI II level used in a previous pilot study were randomly shuffled and rank ordered. Percentile, conjoint/cluster and graphic analyses were performed. All three analyses illustrated consumer ranking followed a bimodal distribution. Ranking for two levels with physical assistance and two levels with a walker were bimodal with a difference of five to six ranks between consumer subgroups (quartile analysis). The larger cluster (N=20) showed preference for walking with assistance over the smaller cluster (N=12), whose preference was walking without assistance and more devices. In all, 64% (27/42) of consumers ranked WISCI II level with no devices or braces and 1 person assistance higher than multiple levels of the WISCI II requiring no assistance. These results were unexpected, as the hypothesis was that consumers would rank independent walking higher than walking with assistance. Consumer preference for walking function should be considered in addition to objective measures in designing SCI trials that use significant improvement in walking function as an outcome measure.

Intensive exercise program after spinal cord injury (“Full-On”): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Rehabilitation after spinal cord injury (SCI) has traditionally involved teaching compensatory strategies for identified impairments and deficits in order to improve functional independence. There is some evidence that regular and intensive activity-based therapies, directed at activation of the paralyzed extremities, promotes neurological improvement. The aim of this study is to compare the effects of a 12-week intensive activity-based therapy program for the whole body with a program of upper body exercise. Methods/Design A multicenter, parallel group, assessor-blinded randomized controlled trial will be conducted. One hundred eighty-eight participants with spinal cord injury, who have completed their primary rehabilitation at least 6 months prior, will be recruited from five SCI units in Australia and New Zealand. Participants will be randomized to an experimental or control group. Experimental participants will receive a 12-week program of intensive exercise for the whole body, including locomotor training, trunk exercises and functional electrical stimulation-assisted cycling. Control participants will receive a 12-week intensive upper body exercise program. The primary outcome is the American Spinal Injuries Association (ASIA) Motor Score. Secondary outcomes include measurements of sensation, function, pain, psychological measures, quality of life and cost effectiveness. All outcomes will be measured at baseline, 12 weeks, 6 months and 12 months by blinded assessors. Recruitment commenced in January 2011. Discussion The results of this trial will determine the effectiveness of a 12-week program of intensive exercise for the whole body in improving neurological recovery after spinal cord injury. Trial registration NCT01236976 (10 November 2010), ACTRN12610000498099 (17 June 2010). PMID:24025260

Cross-cultural differences in preference for recovery of mobility among spinal cord injury rehabilitation professionals.

PubMed

Ditunno, P L; Patrick, M; Stineman, M; Morganti, B; Townson, A F; Ditunno, J F

2006-09-01

Direct observation of a constrained consensus-building process in three culturally independent five-person panels of rehabilitation professionals from the US, Italy and Canada. To illustrate cultural differences in belief among rehabilitation professionals about the relative importance of alternative functional goals during spinal cord injury (SCI) rehabilitation. Spinal Cord Injury Units in Philadelphia-USA, Rome-Italy and Vancouver-Canada. Each of the three panels came to independent consensus about recovery priorities in SCI utilizing the features resource trade-off game. The procedure involves trading imagined levels of independence (resources) across different functional items (features) assuming different stages of recovery. Sphincter management was of primary importance to all three groups. The Italian and Canadian rehabilitation professionals, however, showed preference for walking over wheelchair mobility at lower stages of assumed recovery, whereas the US professionals set wheelchair independence at a higher priority than walking. These preliminary results suggest cross-cultural recovery priority differences among SCI rehabilitation professionals. These dissimilarities in preference may reflect disparities in values, cultural expectations and health care policies.

Cardiorespiratory Fitness and Unintentional Nonfatal Injury Among the United States Air Force Active Duty

DTIC Science & Technology

2005-10-01

it follows that a sedentary lifestyle contributes to the decline in cardiorespiratory function characterized by decreases in VO2max, muscle mass and...to the musculoskeletal region of the spinal column as these injuries have been found to be associated with a sedentary lifestyle (Garg A and Moore JS

Client-centred assessment and the identification of meaningful treatment goals for individuals with a spinal cord injury

PubMed Central

Donnelly, Catherine; Eng, Janice J; Hall, Jill; Alford, Lindsay; Giachino, Rob; Norton, Kathy; Kerr, Debbie Scott

2011-01-01

Study Design Retrospective analysis. Objectives 1) describe the self-care, productivity and leisure problems identified by individuals with a spinal cord injury during rehabilitation, 2) describe the perceived level of satisfaction and performance with self-care, productivity and leisure activities following a spinal cord injury, 3) quantify the relationship between the Canadian Occupational Performance Measure (COPM), a client-centred, individualized measure of function, and the Functional Independence Measure (FIM). Setting Tertiary rehabilitation centre, spinal cord injury unit, GF Strong Rehabilitation Centre, Vancouver, Canada. Methods Health records from 41 individuals with a SCI admitted between 2000 and 2002 were reviewed. Information was obtained from assessments performed on admission and discharge. Self-care, productivity and leisure problems identified by individuals with a SCI were described and their perceived level of performance and satisfaction was calculated. The relationship between the COPM and the FIM was measured by the Pearson product correlation. Results Self-care goals were identified most frequently (79%) followed by productivity (12%) and leisure (9%) goals. The top three problems identified by individuals with a SCI were functional mobility (including transfers and wheelchair use), dressing and grooming. A fair relationship was found between the COPM and the FIM (r between .351 to .514, p<.05) Conclusions The results highlight the importance of including a client-centred outcome measure in the assessment of individual’s with a SCI. Initial support is provided for use of the COPM in individuals with a SCI. PMID:14993893

Duration and functional outcome of spinal cord injury rehabilitation in the Netherlands.

PubMed

Post, Marcel W M; Dallmeijer, Annet J; Angenot, Edmond L D; van Asbeck, Floris W A; van der Woude, Lucas H V

2005-01-01

This study describes the length of stay (LOS) and functional outcome of spinal cord injury (SCI) in the Netherlands and its determinants. Data of 157 patients from eight rehabilitation centers were available. Mean age was 40.0 years and 76.4% were traumatic injuries, 39.8% had tetraplegia, and 69.9% had a motor complete SCI. Median LOS was 240 days (interquartile range 164-322). Median motor Functional Independence Measure (FIM) scores at discharge were 37.3 for persons with complete tetraplegia and 69.7 for persons with complete paraplegia. Level and completeness of injury, bed rest because of pressure sores, and LOS were predictors of motor FIM scores. Duration of SCI rehabilitation in the Netherlands is long compared with the literature. Functional outcome appears slightly better in persons with complete tetraplegia, but not in persons with complete paraplegia when compared with data from the United States. International studies are necessary to reveal strengths and weaknesses of SCI rehabilitation systems in different countries.

A validity study of the Spanish-World Health Organization Quality of Life short version instrument in persons with traumatic spinal cord injury.

PubMed

Salvador-De La Barrera, Sebastián; Mora-Boga, Rubén; Ferreiro-Velasco, Mª Elena; Seoane-Pillado, Teresa; Montoto-Marqués, Antonio; Rodríguez-Sotillo, Antonio; Pertega Díaz, Sonia

2018-05-23

This was a psychometric study. To determine the validity of the Spanish version of the World Health Organization Quality of Life instrument (WHOQOL-BREF) for its use in persons with traumatic spinal cord injury and, as secondary objectives, to correlate the results with variables such as functional status, psychological well-being, and social support. Spinal Cord Injury Unit, Complejo Hospitalario Universitario de A Coruña, Galicia (Spain). Fifty-four people with spinal cord injury were enrolled in this study. Relevant variables were analyzed based on the scores reported by each participant in the Spanish versions of the WHOQOL-BREF questionnaire, the Spinal Cord Independence Measure, the Hospital Anxiety and Depression Scale (HADS), and the Duke-UNC Functional and Social Support Questionnaire. Both parametric and non-parametric tests were used to compare various variables. The instrument's internal consistency and test-retest reliability were also confirmed. The mean scores of each domain of the WHOQOL-BREF were lower, but nonsignificant, among people who need help to perform activities of daily living. The correlation between the scores obtained in the "Psychological" domain and the items of the HADS scale was significant. Significant differences were also observed when comparing the results of the "Social relationships" and "Environment" domains among people with low scores in the Duke questionnaire. Both an adequate consistency (Cronbach's α: 0.887) and test-retest reliability were demonstrated. The Spanish version of the WHOQOL-BREF questionnaire is useful and reliable to evaluate the quality of life of persons with spinal cord injuries in our population of Spanish-speaking people.

Reorganization of the human central nervous system.

PubMed

Schalow, G; Zäch, G A

2000-10-01

The key strategies on which the discovery of the functional organization of the central nervous system (CNS) under physiologic and pathophysiologic conditions have been based included (1) our measurements of phase and frequency coordination between the firings of alpha- and gamma-motoneurons and secondary muscle spindle afferents in the human spinal cord, (2) knowledge on CNS reorganization derived upon the improvement of the functions of the lesioned CNS in our patients in the short-term memory and the long-term memory (reorganization), and (3) the dynamic pattern approach for re-learning rhythmic coordinated behavior. The theory of self-organization and pattern formation in nonequilibrium systems is explicitly related to our measurements of the natural firing patterns of sets of identified single neurons in the human spinal premotor network and re-learned coordinated movements following spinal cord and brain lesions. Therapy induced cell proliferation, and maybe, neurogenesis seem to contribute to the host of structural changes during the process of re-learning of the lesioned CNS. So far, coordinated functions like movements could substantially be improved in every of the more than 100 patients with a CNS lesion by applying coordination dynamic therapy. As suggested by the data of our patients on re-learning, the human CNS seems to have a second integrative strategy for learning, re-learning, storing and recalling, which makes an essential contribution of the functional plasticity following a CNS lesion. A method has been developed by us for the simultaneous recording with wire electrodes of extracellular action potentials from single human afferent and efferent nerve fibres of undamaged sacral nerve roots. A classification scheme of the nerve fibres in the human peripheral nervous system (PNS) could be set up in which the individual classes of nerve fibres are characterized by group conduction velocities and group nerve fibre diameters. Natural impulse patterns of several identified single afferent and efferent nerve fibres (motoneuron axons) were extracted from multi-unit impulse patterns, and human CNS functions could be analyzed under physiologic and pathophysiologic conditions. With our discovery of premotor spinal oscillators it became possible to judge upon CNS neuronal network organization based on the firing patterns of these spinal oscillators and their driving afferents. Since motoneurons fire occasionally for low activation and oscillatory for high activation, the coherent organization of subnetworks to generate macroscopic function is very complex and for the time being, may be best described by the theory of coordination dynamics. Since oscillatory firing has also been observed by us in single motor unit firing patterns measured electromyographically, it seems possible to follow up therapeutic intervention in patients with spinal cord and brain lesions not only based on the activity levels and phases of motor programs during locomotion but also based on the physiologic and pathophysiologic firing patterns and recruitment of spinal oscillators. The improvement of the coordination dynamics of the CNS can be partly measured directly by rhythmicity upon the patient performing rhythmic movements coordinated up to milliseconds. Since rhythmic dynamic, coordinated, stereotyped movements are mainly located in the spinal cord and only little supraspinal drive is necessary to initiate, maintain, and terminate them, rhythmic, dynamic, coordinated movements were used in therapy to enforce reorganization of the lesioned CNS by improving the self-organization and relative coordination of spinal oscillators (and their interactions with occasionally firing motoneurons) which became pathologic in their firing following CNS lesion. Paraparetic, tetraparetic spinal cord and brain-lesioned patients re-learned running and other movements by an oscillator formation and coordination dynamic therapy. Our development in neurorehabilitation is in accordance with those of theoretical and computational neurosciences which deal with the self-organization of neuronal networks. In particular, jumping on a springboard 'in-phase' and in 'anti-phase' to re-learn phase relations of oscillator coupling can be understood in the framework of the Haken-Kelso-Bunz coordination dynamic model. By introducing broken symmetry, intention, learning and spasticity in the landscape of the potential function of the integrated CNS activity, the change in self-organization becomes understandable. Movement patterns re-learned by oscillator formation and coordination dynamic therapy evolve from reorganization and regeneration of the lesioned CNS by cooperative and competitive interplay between intrinsic coordination dynamics, extrinsic therapy related inputs with physiologic re-afferent input, including intention, motivation, supervised learning, interpersonal coordination, and genetic constraints including neurogenesis. (ABSTRACT TRUNCATED)

A comparison of perceptions of quality of life among adults with spinal cord injury in the United States versus the United Kingdom.

PubMed

Palimaru, Alina; Cunningham, William E; Dillistone, Marcus; Vargas-Bustamante, Arturo; Liu, Honghu; Hays, Ron D

2017-11-01

To identify which aspects of life are most important to adults with spinal cord injury (SCI) and compare perspectives in the United States and the United Kingdom. We conducted 20 in-depth interviews with adults with SCI (ten in the US and ten in the UK). Verbatim transcriptions were independently analyzed line-by-line by two coders using an inductive approach. Codes were grouped into themes about factors that constitute and affect quality of life (QOL). Five overarching themes emerged: describing QOL in the context of SCI; functional adjustment; medical care; financial resources; and socio-political issues. Twenty subthemes emerged on factors that affect QOL. Participants in both samples identified medical care as a key influence on QOL. The US group talked about a predominantly negative influence (e.g., fragmented primary and specialist care, insurance constraints, bureaucracy), whereas UK interviewees mentioned a predominantly positive influence (e.g., universal provision, including free and continuous care, free wheelchairs and home care, and length of rehabilitation commensurate with level of injury). Functional adjustment, such as physical and mental adjustment post-discharge and aging with SCI, was another important contributor to QOL, and varied by country. Most US interviewees reported poor knowledge about self-care post-discharge and poor quality of home adaptations compared to the UK group. For adults living with SCI, good QOL is essential for successful rehabilitation. Differences between interviewees from the two countries in perceived medical care and functional adjustment suggest that factors affecting QOL may relate to broader health system characteristics.

An Implanted Upper-Extremity Neuroprosthesis Using Myoelectric Control

PubMed Central

Kilgore, Kevin L.; Hoyen, Harry A.; Bryden, Anne M.; Hart, Ronald L.; Keith, Michael W.; Peckham, P. Hunter

2009-01-01

Purpose The purpose of this study was evaluate the potential of a second-generation implantable neuroprosthesis that provides improved control of hand grasp and elbow extension for individuals with cervical level spinal cord injury. The key feature of this system is that users control their stimulated function through electromyographic (EMG) signals. Methods The second-generation neuroprosthesis consists of 12 stimulating electrodes, 2 EMG signal recording electrodes, an implanted stimulator-telemeter device, an external control unit, and a transmit/receive coil. The system was implanted in a single surgical procedure. Functional outcomes for each subject were evaluated in the domains of body functions and structures, activity performance, and societal participation. Results Three individuals with C5/C6 spinal cord injury received system implantation with subsequent prospective evaluation for a minimum of 2 years. All 3 subjects demonstrated that EMG signals can be recorded from voluntary muscles in the presence of electrical stimulation of nearby muscles. Significantly increased pinch force and grasp function was achieved for each subject. Functional evaluation demonstrated improvement in at least 5 activities of daily living using the Activities of Daily Living Abilities Test. Each subject was able to use the device at home. There were no system failures. Two of 6 EMG electrodes required surgical revision because of suboptimal location of the recording electrodes. Conclusions These results indicate that a neuroprosthesis with implanted myoelectric control is an effective method for restoring hand function in midcervical level spinal cord injury. Type of study/level of evidence Therapeutic IV. PMID:18406958

The influence of shoulder pain on functional limitation, perceived health, and depressive mood in patients with traumatic paraplegia

PubMed Central

Wang, Jia-Chi; Chan, Rai-Chi; Tsai, Yun-An; Huang, Wen-Cheng; Cheng, Henrich; Wu, Han-Lin

2015-01-01

Objective To assess whether functional activity, perceived health, and depressive symptoms differ between individuals with traumatic paraplegia with and without shoulder pain. Design Cross sectional and comparative investigation using the unified questionnaire. Setting Neural Regeneration and Repair Division unit of Taipei Veterans General Hospital in Taiwan. Participants Seventy-six patients with paraplegia (23 with and 53 without shoulder pain) who had experienced spinal cord injury at American Spinal Injury Association Impairment Scale T2 to T12 neurologic level (at least 6 months previously). Outcome measures Spinal Cord Independence Measure (SCIM), a single item from the Medical Outcomes Study 36-Item Short-Form Health Survey, and Patient Health Questionnaire-9 (PHQ-9) depression scale. Results Shoulder pain was prevalent in 30% patients. Patients with shoulder pain had significantly worse perceived health and greater depressive symptoms than those without. No significant difference was found in functional ability between groups. Greater shoulder pain intensity was related to higher depressive scores (r = 0.278, P = 0.017) and lower self-perceived health scores (r = −0.433, P < 0.001) but not SCIM scores (P = 0.342). Conclusion Although shoulder pain was unrelated to functional limitation, it was associated with lower perceived health and higher depressive mood levels. PMID:25296991

Effects of paraplegia on quality of life and family economy among patients with spinal cord injuries in selected hospitals of Sri Lanka.

PubMed

Kalyani, H H N; Dassanayake, S; Senarath, U

2015-06-01

The study was conducted with the aim of assessing the effects of paraplegia caused by spinal cord injuries on the quality of life of patients and their family economy. A descriptive cross-sectional study. The study was carried out in Accident Service, Orthopedic and Neurosurgery Units of the National Hospital of Sri Lanka and the Spinal Injury Unit of Rehabilitation Hospital Ragama. One hundred traumatic paraplegic patients were included as the study sample. Modified Ferrans and Powers quality of life index: spinal cord injury version was used to measure the quality of life. Pre- and post-family economic data were collected using an interviewer-administered questionnaire. Quality of Life was calculated under four major components. Paraplegics' family component (mean=3.50) and social, economic aspects (mean=3.24) are considerably good when compared with health and functioning (mean=2.83) and psychological (mean=2.78) components. Also the study revealed that expenditures are significantly high (P=0.001) and income is significantly less (P=0.001) after injury than before. Quality of life is relatively good on family and social aspects, whereas the physical and psychological aspects are somewhat poor. Regarding family economy, expenses are significantly high and earnings are significantly less after the injury. Contribution to the income from self-employment shows the most significant decline. Findings suggest that the family economy of such patients should be supported.

Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on Functional Recovery after Spinal Cord Injury

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-12-1-0587 TITLE: Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on Functional Recovery after Spinal Cord...3. DATES COVERED (From - To) 30Sep2014 - 29Sep2015 4. TITLE AND SUBTITLE Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on...ABSTRACT Essentially all spinal cord injured patients receive stretching therapies beginning within the first few weeks post-injury. Despite this fact

Clinical interpretation of the Spinal Cord Injury Functional Index (SCI-FI).

PubMed

Fyffe, Denise; Kalpakjian, Claire Z; Slavin, Mary; Kisala, Pamela; Ni, Pengsheng; Kirshblum, Steven C; Tulsky, David S; Jette, Alan M

2016-09-01

To provide validation of functional ability levels for the Spinal Cord Injury - Functional Index (SCI-FI). Cross-sectional. Inpatient rehabilitation hospital and community settings. A sample of 855 individuals with traumatic spinal cord injury enrolled in 6 rehabilitation centers participating in the National Spinal Cord Injury Model Systems Network. Not Applicable. Spinal Cord Injury-Functional Index (SCI-FI). Cluster analyses identified three distinct groups that represent low, mid-range and high SCI-FI functional ability levels. Comparison of clusters on personal and other injury characteristics suggested some significant differences between groups. These results strongly support the use of SCI-FI functional ability levels to document the perceived functional abilities of persons with SCI. Results of the cluster analysis suggest that the SCI-FI functional ability levels capture function by injury characteristics. Clinical implications regarding tracking functional activity trajectories during follow-up visits are discussed.

Numb rats walk - a behavioural and fMRI comparison of mild and moderate spinal cord injury.

PubMed

Hofstetter, Christoph P; Schweinhardt, Petra; Klason, Tomas; Olson, Lars; Spenger, Christian

2003-12-01

Assessment of sensory function serves as a sensitive measure for predicting the functional outcome following spinal cord injury in patients. However, little is known about loss and recovery of sensory function in rodent spinal cord injury models as most tests of sensory functions rely on behaviour and thus motor function. We used functional magnetic resonance imaging (fMRI) to investigate cortical and thalamic BOLD-signal changes in response to limb stimulation following mild or moderate thoracic spinal cord weight drop injury in Sprague-Dawley rats. While there was recovery of close to normal hindlimb motor function as determined by open field locomotor testing following both degrees of injury, recovery of hindlimb sensory function as determined by fMRI and hot plate testing was only seen following mild injury and not following moderate injury. Thus, moderate injury can lead to near normal hindlimb motor function in animals with major sensory deficits. Recovered fMRI signals following mild injury had a partly altered cortical distribution engaging also ipsilateral somatosensory cortex and the cingulate gyrus. Importantly, thoracic spinal cord injury also affected sensory representation of the upper nonaffected limbs. Thus, cortical and thalamic activation in response to forelimb stimulation was significantly increased 16 weeks after spinal cord injury compared to control animals. We conclude that both forelimb and hindlimb cortical sensory representation is altered following thoracic spinal cord injury. Furthermore tests of sensory function that are independent of motor behaviour are needed in rodent spinal cord injury research.

Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-2-0132 TITLE: Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury...Sept 2015 4. TITLE AND SUBTITLE Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury 5a...evaluate the restoration of bladder and bowel function using electrical stimulation and block after spinal cord injury in human subjects. All staff

Simultaneous Brain–Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning

PubMed Central

Cohen-Adad, Julien; Marchand-Pauvert, Veronique; Benali, Habib; Doyon, Julien

2015-01-01

The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6–C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain–spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations. PMID:26125597

Simultaneous Brain-Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning.

PubMed

Vahdat, Shahabeddin; Lungu, Ovidiu; Cohen-Adad, Julien; Marchand-Pauvert, Veronique; Benali, Habib; Doyon, Julien

2015-06-01

The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6-C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain-spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations.

Patients, doctors, and therapists perceptions of professional roles in spinal cord injury rehabilitation: do they agree?

PubMed

Pellatt, Glynis Collis

2007-03-01

Spinal cord injury is a devastating condition, requiring extensive rehabilitation from a range of health care professionals. However, it is unclear if patients view the professionals' input into their rehabilitation in the same way as those professionals. This paper presents findings from a qualitative study into patient participation in spinal cord injury rehabilitation. The aim of the part of the study reported here was to identify whether there is agreement between health care professionals and patients perceptions of professional roles in spinal cord injury rehabilitation. Results are presented from semi-structured interviews conducted with five doctors, five physiotherapists, three occupational therapists and 20 patients in a spinal cord injury unit in England. Findings suggest considerable agreement between professionals and patients about the role those professionals play in their rehabilitation. Physiotherapists are perceived to be key to rehabilitation, occupational therapists focus on hand function but physiotherapists and occupational therapists complement each other. Doctors coordinate the team yet reduce their input as patients move out of the acute phase into rehabilitation. There are some tensions but the early input of these professionals into patients' rehabilitation may help to develop understanding of roles. Congruence between patients and professionals may mean that patients have realistic expectations and encourage a more equal relationship between them.

Early intensive hand rehabilitation after spinal cord injury ("Hands On"): a protocol for a randomised controlled trial.

PubMed

Harvey, Lisa A; Dunlop, Sarah A; Churilov, Leonid; Hsueh, Ya-Seng Arthur; Galea, Mary P

2011-01-17

Loss of hand function is one of the most devastating consequences of spinal cord injury. Intensive hand training provided on an instrumented exercise workstation in conjunction with functional electrical stimulation may enhance neural recovery and hand function. The aim of this trial is to compare usual care with an 8-week program of intensive hand training and functional electrical stimulation. A multicentre randomised controlled trial will be undertaken. Seventy-eight participants with recent tetraplegia (C2 to T1 motor complete or incomplete) undergoing inpatient rehabilitation will be recruited from seven spinal cord injury units in Australia and New Zealand and will be randomised to a control or experimental group. Control participants will receive usual care. Experimental participants will receive usual care and an 8-week program of intensive unilateral hand training using an instrumented exercise workstation and functional electrical stimulation. Participants will drive the functional electrical stimulation of their target hands via a behind-the-ear bluetooth device, which is sensitive to tooth clicks. The bluetooth device will enable the use of various manipulanda to practice functional activities embedded within computer-based games and activities. Training will be provided for one hour, 5 days per week, during the 8-week intervention period. The primary outcome is the Action Research Arm Test. Secondary outcomes include measurements of strength, sensation, function, quality of life and cost effectiveness. All outcomes will be taken at baseline, 8 weeks, 6 months and 12 months by assessors blinded to group allocation. Recruitment commenced in December 2009. The results of this trial will determine the effectiveness of an 8-week program of intensive hand training with functional electrical stimulation. NCT01086930 (12th March 2010)ACTRN12609000695202 (12th August 2009).

Fibrocartilaginous embolic myelopathy: demographics, clinical presentation, and functional outcomes.

PubMed

Moore, Brittany J; Batterson, Anna M; Luetmer, Marianne T; Reeves, Ronald K

2018-05-25

Retrospective cohort study. To describe the demographics, clinical presentation, and functional outcomes of fibrocartilaginous embolic myelopathy (FCEM). Academic inpatient rehabilitation unit in the midwestern United States. We retrospectively searched our database to identify patients admitted between January 1, 1995 and March 31, 2016, with a high probability of FCEM. Demographic, clinical, and functional outcome measures, including Functional Independence Measure (FIM) information was obtained by chart review. We identified 31 patients with findings suggestive of FCEM (52% male), which was 2% of the nontraumatic spinal cord injury population admitted to inpatient rehabilitation. The age distribution was bimodal, with peaks in the second and sixth-to-seventh decades. The most common clinical presentation was acute pain and rapid progression of neurologic deficits consistent with a vascular myelopathy. Only three patients (10%) had FCEM documented as a diagnostic possibility. Most patients had paraplegia and neurologically incomplete injuries and were discharged to home. Nearly half of the patients required no assistive device for bladder management at discharge, but most were discharged with medications for bowel management. Median FIM walking locomotion score for all patients was 5, but most patients were discharged using a wheelchair for primary mobility. Median motor FIM subscale score was 36 at admission and 69 at discharge, with a median motor efficiency of 1.41. FCEM may be underdiagnosed and should be considered in those with the appropriate clinical presentation, because their functional outcomes may be more favorable than those with other causes of spinal cord infarction.

Shriners Hospital Spinal Cord Injury Self Care Manual.

ERIC Educational Resources Information Center

Fox, Carol

This manual is intended for young people with spinal cord injuries who are receiving rehabilitation services within the Spinal Cord Injury Unit at Shriners Hospital (San Francisco, California). An introduction describes the rehabilitation program, which includes family conferences, an individualized program, an independent living program,…

Interplay of upper and lower motor neuron degeneration in amyotrophic lateral sclerosis.

PubMed

de Carvalho, Mamede; Poliakov, Artiom; Tavares, Cristiano; Swash, Michael

2017-11-01

We studied motor unit recruitment to test a new method to identify motor unit firing rate (FR) variability. We studied 68 ALS patients, with and without upper neuron signs (UMN) in lower limbs, 24 patients with primary lateral sclerosis (PLS), 13 patients with spinal cord lesion and 39 normal subjects. All recordings were made from tibialis anterior muscles of normal strength. Subjects performed a very slight contraction in order to activate 2 motor units in each recording. 5-7 motor unit pairs were recorded in each subject. Mean consecutive differences (MCD) were calculated for each pair of potentials. The mean MCD for each muscle was estimated as the mean from the total number of pairs recorded. Ap value<0.01 was accepted as significant. MCD of FR frequency was less in the subjects with spinal cord lesion and PLS. In addition, the FR frequency of the 1st motor unit in a pair of units was markedly reduced in PLS, and in subjects with spinal cord lesions. These results support a lower threshold and reduced FR fluctuation in spinal motor neurons of spastic patients. This method can be developed for detection of UMN lesions. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Comparison of Motor-Evoked Potentials Versus Somatosensory-Evoked Potentials as Early Indicators of Neural Compromise in Rat Model of Spinal Cord Compression.

PubMed

Morris, Susan H; Howard, Jason J; El-Hawary, Ron

2017-03-15

Randomized controlled study comparing the efficacy of intraoperative somatosensory-evoked potentials (SSEPs) versus transcranial motor-evoked potentials (TcMEPs) as early indicators of neural compromise and predictors of postoperative function in a rat model of spinal cord compression. To compare the relative efficacy of SSEPs and TcMEPs to detect spinal cord compromise and predict postoperative functional deficit after spinal cord compression. There is controversy regarding the efficacy of SSEPs versus TcMEPs to detect intraoperative spinal cord compromise and predict functional outcomes. Previous trials provide some guidance as to the role of each modality in spinal cord monitoring but randomized controlled trials, which are not feasible in humans, are lacking. Twenty-four adult male Wistar rats were evenly divided into three experimental groups and one control group. The experimental groups were determined according to the length of time that 100% TcMEP signal loss was maintained: 0, 5, or 15 minutes. All animals had standardized preoperative functional testing. Spinal cord compromise was initiated utilizing a validated protocol, which involved compression via a balloon catheter introduced into the thoracic sublaminar space. Both SSEPs and TcMEPs were recorded during cord compression for each experimental group. Functional behavioral testing using two validated methods (tilt and modified Tarlov) was repeated 24 hours after termination of spinal cord compression. Post hoc, animals were redistributed into two functional subgroups, noncompromised and compromised, for statistical analysis. TcMEPs consistently detected spinal cord compromise either in advance of or at the same time as SSEPs; however, the delay in SSEP response was not significant for cases when compromised postoperative function resulted. Both SSEP and TcMEP amplitude recovery correlated well with postoperative functional scores. TcMEPs are more sensitive to spinal cord compromise than SSEPs, but the recovery profiles of both SSEP and TcMEP amplitudes are good predictors of postoperative function. 2.

Needle puncture in rabbit functional spinal units alters rotational biomechanics.

PubMed

Hartman, Robert A; Bell, Kevin M; Quan, Bichun; Nuzhao, Yao; Sowa, Gwendolyn A; Kang, James D

2015-04-01

An in vitro biomechanical study for rabbit lumbar functional spinal units (FSUs) using a robot-based spine testing system. To elucidate the effect of annular puncture with a 16 G needle on mechanical properties in flexion/extension, axial rotation, and lateral bending. Needle puncture of the intervertebral disk has been shown to alter mechanical properties of the disk in compression, torsion, and bending. The effect of needle puncture in FSUs, where intact spinal ligaments and facet joints may mitigate or amplify these changes in the disk, on spinal motion segment stability subject to physiological rotations remains unknown. Rabbit FSUs were tested using a robot testing system whose force/moment and position precision were assessed to demonstrate system capability. Flexibility testing methods were developed by load-to-failure testing in flexion/extension, axial rotation, and lateral bending. Subsequent testing methods were used to examine a 16 G needle disk puncture and No. 11 blade disk stab (positive control for mechanical disruption). Flexibility testing was used to assess segmental range-of-motion (degrees), neutral zone stiffness (N m/degrees) and width (degrees and N m), and elastic zone stiffness before and after annular injury. The robot-based system was capable of performing flexibility testing on FSUs-mean precision of force/moment measurements and robot system movements were <3% and 1%, respectively, of moment-rotation target values. Flexibility moment targets were 0.3 N m for flexion and axial rotation and 0.15 N m for extension and lateral bending. Needle puncture caused significant (P<0.05) changes only in flexion/extension range-of-motion and neutral zone stiffness and width (N m) compared with preintervention. No. 11 blade-stab significantly increased range-of-motion in all motions, decreased neutral zone stiffness and width (N m) in flexion/extension, and increased elastic zone stiffness in flexion and lateral bending. These findings suggest that disk puncture and stab can destabilize FSUs in primary rotations.

[Spanish validation of the International Spinal Cord Injury Pulmonary Function Basic Data Set questionnaire for the study of the repercussion of spinal cord injury in the respiratory system].

PubMed

Gómez Garrido, Alba; León Espitia, Ana María; Montesinos Magraner, Lluïsa; Ramirez Galceran, Lucrecia; Soler Canudes, Emilia; González Viejo, Miguel Angel

2015-12-07

The dysfunction of the respiratory system and the breathing complications in persons with injured spinal cord has an effect on the morbidity and the mortality of the disease. The objectives were: 1) to translate to Spanish and validate the questionnaire of international consensus: International Spinal Cord Injury Pulmonary Function Basic Data Set, and 2) to determine the influence of chronic spinal cord injury in the respiratory system in terms of respiratory functionalism. Translation to Spanish and validation of the questionnaire of international consensus intended for the study of the pulmonary function in spinal cord injury disease. We tested the reliability of that questionnaire. We conducted a descriptive transversal study to determine the degree of involvement of the respiratory system in spinal cord injury. A percentage of 91.9 did not have any respiratory pathology before spinal cord injury and 54.8% of patients smoked. A percentage of 27.4 of patients presented breathing complications one year after the injury. Results of the respiratory function tests were: FVC 67%, FEV1 72% and PEF 70%. Concordance and reliability were 98%. The Spanish version of the questionnaire of international consensus about the pulmonary function is a useful tool for the study of the respiratory involvement in spinal cord injury. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Clinical interpretation of the Spinal Cord Injury Functional Index (SCI-FI)

PubMed Central

Fyffe, Denise; Kalpakjian, Claire Z.; Slavin, Mary; Kisala, Pamela; Ni, Pengsheng; Kirshblum, Steven C.; Tulsky, David S.; Jette, Alan M.

2016-01-01

Objective: To provide validation of functional ability levels for the Spinal Cord Injury – Functional Index (SCI-FI). Design: Cross-sectional. Setting: Inpatient rehabilitation hospital and community settings. Participants: A sample of 855 individuals with traumatic spinal cord injury enrolled in 6 rehabilitation centers participating in the National Spinal Cord Injury Model Systems Network. Interventions: Not Applicable. Main Outcome Measures: Spinal Cord Injury-Functional Index (SCI-FI). Results: Cluster analyses identified three distinct groups that represent low, mid-range and high SCI-FI functional ability levels. Comparison of clusters on personal and other injury characteristics suggested some significant differences between groups. Conclusions: These results strongly support the use of SCI-FI functional ability levels to document the perceived functional abilities of persons with SCI. Results of the cluster analysis suggest that the SCI-FI functional ability levels capture function by injury characteristics. Clinical implications regarding tracking functional activity trajectories during follow-up visits are discussed. PMID:26781769

Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

PubMed Central

Sahin, Murat; Gullu, Huriye; Peker, Kemal; Sayar, Ilyas; Binici, Orhan; Yildiz, Huseyin

2015-01-01

The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia. PMID:26807119

Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

PubMed

Sahin, Murat; Gullu, Huriye; Peker, Kemal; Sayar, Ilyas; Binici, Orhan; Yildiz, Huseyin

2015-11-01

The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia.

Toward standardized reporting for a cohort study on functioning: The Swiss Spinal Cord Injury Cohort Study.

PubMed

Prodinger, Birgit; Ballert, Carolina S; Brach, Mirjam; Brinkhof, Martin W G; Cieza, Alarcos; Hug, Kerstin; Jordan, Xavier; Post, Marcel W M; Scheel-Sailer, Anke; Schubert, Martin; Tennant, Alan; Stucki, Gerold

2016-02-01

Functioning is an important outcome to measure in cohort studies. Clear and operational outcomes are needed to judge the quality of a cohort study. This paper outlines guiding principles for reporting functioning in cohort studies and addresses some outstanding issues. Principles of how to standardize reporting of data from a cohort study on functioning, by deriving scores that are most useful for further statistical analysis and reporting, are outlined. The Swiss Spinal Cord Injury Cohort Study Community Survey serves as a case in point to provide a practical application of these principles. Development of reporting scores must be conceptually coherent and metrically sound. The International Classification of Functioning, Disability and Health (ICF) can serve as the frame of reference for this, with its categories serving as reference units for reporting. To derive a score for further statistical analysis and reporting, items measuring a single latent trait must be invariant across groups. The Rasch measurement model is well suited to test these assumptions. Our approach is a valuable guide for researchers and clinicians, as it fosters comparability of data, strengthens the comprehensiveness of scope, and provides invariant, interval-scaled data for further statistical analyses of functioning.

Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury

PubMed Central

Ferguson, Adam R.; Huie, J. Russell; Crown, Eric D.; Baumbauer, Kyle M.; Hook, Michelle A.; Garraway, Sandra M.; Lee, Kuan H.; Hoy, Kevin C.; Grau, James W.

2012-01-01

Synaptic plasticity within the spinal cord has great potential to facilitate recovery of function after spinal cord injury (SCI). Spinal plasticity can be induced in an activity-dependent manner even without input from the brain after complete SCI. A mechanistic basis for these effects is provided by research demonstrating that spinal synapses have many of the same plasticity mechanisms that are known to underlie learning and memory in the brain. In addition, the lumbar spinal cord can sustain several forms of learning and memory, including limb-position training. However, not all spinal plasticity promotes recovery of function. Central sensitization of nociceptive (pain) pathways in the spinal cord may emerge in response to various noxious inputs, demonstrating that plasticity within the spinal cord may contribute to maladaptive pain states. In this review we discuss interactions between adaptive and maladaptive forms of activity-dependent plasticity in the spinal cord below the level of SCI. The literature demonstrates that activity-dependent plasticity within the spinal cord must be carefully tuned to promote adaptive spinal training. Prior work from our group has shown that stimulation that is delivered in a limb position-dependent manner or on a fixed interval can induce adaptive plasticity that promotes future spinal cord learning and reduces nociceptive hyper-reactivity. On the other hand, stimulation that is delivered in an unsynchronized fashion, such as randomized electrical stimulation or peripheral skin injuries, can generate maladaptive spinal plasticity that undermines future spinal cord learning, reduces recovery of locomotor function, and promotes nociceptive hyper-reactivity after SCI. We review these basic phenomena, how these findings relate to the broader spinal plasticity literature, discuss the cellular and molecular mechanisms, and finally discuss implications of these and other findings for improved rehabilitative therapies after SCI. PMID:23087647

Complete segmental resection of the spine, including the spinal cord, for telangiectatic osteosarcoma: a report of 2 cases.

PubMed

Murakami, Hideki; Tomita, Katsuro; Kawahara, Norio; Oda, Makoto; Yahata, Tetsutaro; Yamaguchi, Takehiko

2006-02-15

Two case reports of telangiectatic osteosarcoma treated with complete segmental resection of the spine, including the spinal cord. To report the en bloc tumor excision, including the spinal cord, for telangiectatic osteosarcoma, and discuss the indication of cord transection and influence after cutting the spinal cord. To our knowledge, there are no previous reports describing telangiectatic osteosarcoma of the spine and the subsequent en bloc excision of the spine, including the spinal cord. The clinical and radiographic presentations of 2 cases with telangiectatic osteosarcoma are presented. Because these 2 cases already had complete paralysis for at least 1 month, it was suspected that there was no possibility of recovering spinal cord function. Complete segmental spinal resection (total en bloc spondylectomy) was performed. At that level, the spinal cord was also cut and resected. En bloc excision of the tumor with a wide margin was achieved in both cases. In the resected specimen, the nerve cells in the spinal cord had lapsed into degenerative necrosis. The pathologic findings showed that there was no hope for recovery of spinal cord function. En bloc spinal resection, including the spinal cord, is an operation allowed when there is no hope for recovery of spinal cord function. This surgery should be accepted as an option in spine tumor surgeries.

Mangiferin attenuates contusive spinal cord injury in rats through the regulation of oxidative stress, inflammation and the Bcl‑2 and Bax pathway.

PubMed

Luo, Yang; Fu, Changfeng; Wang, Zhenyu; Zhang, Zhuo; Wang, Hongxia; Liu, Yi

2015-11-01

Mangiferin has antioxidant, antiviral, apoptosis regulating, anti‑inflammatory, antitumor and antidiabetic effects, which can also inhibit osteoclast formation and bone resorption. However, whether mangiferin ameliorates the neurological pain of spinal cord injury (SCI) in ratS remains to be elucidated. The present study investigated the therapeutic effects of mangiferin on neurological function, the water content of spinal cord, oxidative stress, the expression of inflammatory cytokines and the protein expression of Bcl‑2/Bax in a SCI rat model. In the present study, the Basso, Beattie and Bresnahan scores, and the water content of the spinal cord were used to analyze the therapeutic effects of mangiferin on neurological pain in the SCI rat. The concentrations of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and the serum levels of glutathione peroxidase (GSH‑PX), nuclear factor‑κB p65 unit, tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6 and caspase‑3/9 were detected using commercial kits. The expression levels of Bcl‑2 and Bax were measured using western blot analysis. The results demonstrated that administrating mangiferin began to ameliorate neurological function and the water content of the spinal cord in the SCI rat. The mangiferin‑treated group were found to have lower oxidative stress activity and lower expression levels of inflammatory cytokines, compared with the SCI rat. In addition, mangiferin significantly reduced the protein expression of Bax and promoted the protein expression of Bcl-2 in the SCI rat model. Finally, mangiferin markedly suppressed the expression of caspase‑3/9, indicating that the protective action of mangiferin may be associated with anti‑apoptosis activation. In conclusion, mangiferin attenuated contusive SCI in the rats through regulating oxidative stress, inflammation and the Bcl‑2 and Bax pathway.

Zebrafish transgenic constructs label specific neurons in Xenopus laevis spinal cord and identify frog V0v spinal neurons.

PubMed

Juárez-Morales, José L; Martinez-De Luna, Reyna I; Zuber, Michael E; Roberts, Alan; Lewis, Katharine E

2017-09-01

A correctly functioning spinal cord is crucial for locomotion and communication between body and brain but there are fundamental gaps in our knowledge of how spinal neuronal circuitry is established and functions. To understand the genetic program that regulates specification and functions of this circuitry, we need to connect neuronal molecular phenotypes with physiological analyses. Studies using Xenopus laevis tadpoles have increased our understanding of spinal cord neuronal physiology and function, particularly in locomotor circuitry. However, the X. laevis tetraploid genome and long generation time make it difficult to investigate how neurons are specified. The opacity of X. laevis embryos also makes it hard to connect functional classes of neurons and the genes that they express. We demonstrate here that Tol2 transgenic constructs using zebrafish enhancers that drive expression in specific zebrafish spinal neurons label equivalent neurons in X. laevis and that the incorporation of a Gal4:UAS amplification cassette enables cells to be observed in live X. laevis tadpoles. This technique should enable the molecular phenotypes, morphologies and physiologies of distinct X. laevis spinal neurons to be examined together in vivo. We have used an islet1 enhancer to label Rohon-Beard sensory neurons and evx enhancers to identify V0v neurons, for the first time, in X. laevis spinal cord. Our work demonstrates the homology of spinal cord circuitry in zebrafish and X. laevis, suggesting that future work could combine their relative strengths to elucidate a more complete picture of how vertebrate spinal cord neurons are specified, and function to generate behavior. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1007-1020, 2017. © 2017 Wiley Periodicals, Inc.

Exercise Preconditioning Protects against Spinal Cord Injury in Rats by Upregulating Neuronal and Astroglial Heat Shock Protein 72

PubMed Central

Chang, Cheng-Kuei; Chou, Willy; Lin, Hung-Jung; Huang, Yi-Ching; Tang, Ling-Yu; Lin, Mao-Tsun; Chang, Ching-Ping

2014-01-01

The heat shock protein 72 (HSP 72) is a universal marker of stress protein whose expression can be induced by physical exercise. Here we report that, in a localized model of spinal cord injury (SCI), exercised rats (given pre-SCI exercise) had significantly higher levels of neuronal and astroglial HSP 72, a lower functional deficit, fewer spinal cord contusions, and fewer apoptotic cells than did non-exercised rats. pSUPER plasmid expressing HSP 72 small interfering RNA (SiRNA-HSP 72) was injected into the injured spinal cords. In addition to reducing neuronal and astroglial HSP 72, the (SiRNA-HSP 72) significantly attenuated the beneficial effects of exercise preconditioning in reducing functional deficits as well as spinal cord contusion and apoptosis. Because exercise preconditioning induces increased neuronal and astroglial levels of HSP 72 in the gray matter of normal spinal cord tissue, exercise preconditioning promoted functional recovery in rats after SCI by upregulating neuronal and astroglial HSP 72 in the gray matter of the injured spinal cord. We reveal an important function of neuronal and astroglial HSP 72 in protecting neuronal and astroglial apoptosis in the injured spinal cord. We conclude that HSP 72-mediated exercise preconditioning is a promising strategy for facilitating functional recovery from SCI. PMID:25334068

Modeling the functional repair of nervous tissue in spinal cord injury

NASA Astrophysics Data System (ADS)

Mantila, Sara M.; Camp, Jon J.; Krych, Aaron J.; Robb, Richard A.

2004-05-01

Functional repair of traumatic spinal cord injury (SCI) is one of the most challenging goals in modern medicine. The annual incidence of SCI in the United States is approximately 11,000 new cases. The prevalence of people in the U.S. currently living with SCI is approximately 200,000. Exploring and understanding nerve regeneration in the central nervous system (CNS) is a critical first step in attempting to reverse the devastating consequences of SCI. At Mayo Clinic, a preliminary study of implants in the transected rat spinal cord model demonstrates potential for promoting axon regeneration. In collaborative research between neuroscientists and bioengineers, this procedure holds promise for solving two critical aspects of axon repair-providing a resorbable structural scaffold to direct focused axon repair, and delivery of relevant signaling molecules necessary to facilitate regeneration. In our preliminary study, regeneration in the rat's spinal cord was modeled in three dimensions utilizing an image processing software system developed in the Biomedical Imaging Resource at Mayo Clinic. Advanced methods for image registration, segmentation, and rendering were used. The raw images were collected at three different magnifications. After image processing the individual channels in the scaffold, axon bundles, and macrophages could be identified. Several axon bundles could be visualized and traced through the entire volume, suggesting axonal growth throughout the length of the scaffold. Such information could potentially allow researchers and physicians to better understand and improve the nerve regeneration process for individuals with SCI.

[Research of joint-robotics-based design of biomechanics testing device on human spine].

PubMed

Deng, Guoyong; Tian, Lianfang; Mao, Zongyuan

2009-12-01

This paper introduces the hardware and software of a biomechanical robot-based testing device. The bottom control orders, posture and torque data transmission, and the control algorithms are integrated in a unified visual control platform by Visual C+ +, with easy control and management. By using hybrid force-displacement control method to load the human spine, we can test the organizational structure and the force state of the FSU (Functional spinal unit) well, which overcomes the shortcomings due to the separation of the force and displacement measurement, thus greatly improves the measurement accuracy. Also it is esay to identify the spinal degeneration and the load-bearing impact on the organizational structure of the FSU after various types of surgery.

Effect of deafferentation from spinal anesthesia on pain sensitivity and resting-state functional brain connectivity in healthy male volunteers.

PubMed

Niesters, Marieke; Sitsen, Elske; Oudejans, Linda; Vuyk, Jaap; Aarts, Leon P H J; Rombouts, Serge A R B; de Rover, Mischa; Khalili-Mahani, Najmeh; Dahan, Albert

2014-08-01

Patients may perceive paradoxical heat sensation during spinal anesthesia. This could be due to deafferentation-related functional changes at cortical, subcortical, or spinal levels. In the current study, the effect of spinal deafferentation on sensory (pain) sensitivity was studied and linked to whole-brain functional connectivity as assessed by resting-state functional magnetic resonance imaging (RS-fMRI) imaging. Deafferentation was induced by sham or spinal anesthesia (15 mg bupivacaine injected at L3-4) in 12 male volunteers. RS-fMRI brain connectivity was determined in relation to eight predefined and seven thalamic resting-state networks (RSNs) and measured before, and 1 and 2 h after spinal/sham injection. To measure the effect of deafferentation on pain sensitivity, responses to heat pain were measured at 15-min intervals on nondeafferented skin and correlated to RS-fMRI connectivity data. Spinal anesthesia altered functional brain connectivity within brain regions involved in the sensory discriminative (i.e., pain intensity related) and affective dimensions of pain perception in relation to somatosensory and thalamic RSNs. A significant enhancement of pain sensitivity on nondeafferented skin was observed after spinal anesthesia compared to sham (area-under-the-curve [mean (SEM)]: 190.4 [33.8] versus 13.7 [7.2]; p<0.001), which significantly correlated to functional connectivity changes observed within the thalamus in relation to the thalamo-prefrontal network, and in the anterior cingulate cortex and insula in relation to the thalamo-parietal network. Enhanced pain sensitivity from spinal deafferentation correlated with functional connectivity changes within brain regions involved in affective and sensory pain processing and areas involved in descending control of pain.

Accelerated recovery of sensorimotor function in a dog submitted to quasi-total transection of the cervical spinal cord and treated with PEG.

PubMed

Kim, C-Yoon; Hwang, In-Kyu; Kim, Hana; Jang, Se-Woong; Kim, Hong Seog; Lee, Won-Young

2016-01-01

A case report on observing the recovery of sensory-motor function after cervical spinal cord transection. Laminectomy and transection of cervical spinal cord (C5) was performed on a male beagle weighing 3.5 kg. After applying polyethylene glycol (PEG) on the severed part, reconstruction of cervical spinal cord was confirmed by the restoration of sensorimotor function. Tetraplegia was observed immediately after operation, however, the dog showed stable respiration and survival without any complication. The dog showed fast recovery after 1 week, and recovered approximately 90% of normal sensorimotor function 3 weeks after the operation, although urinary disorder was still present. All recovery stages were recorded by video camera twice a week for behavioral analysis. While current belief holds that functional recovery is impossible after a section greater than 50% at C5-6 in the canine model, this case study shows the possibility of cervical spinal cord reconstruction after near-total transection. Furthermore, this case study also confirms that PEG can truly expedite the recovery of sensorimotor function after cervical spinal cord sections in dogs.

The uniform data system for medical rehabilitation: report of patients with traumatic spinal cord injury discharged from rehabilitation programs in 2002-2010.

PubMed

Granger, Carl V; Karmarkar, Amol M; Graham, James E; Deutsch, Anne; Niewczyk, Paulette; Divita, Margaret A; Ottenbacher, Kenneth J

2012-04-01

This study aimed to provide benchmarking information from a large national sample of patients receiving inpatient rehabilitation after a traumatic spinal cord injury. This was an analysis of secondary data from 891 inpatient medical rehabilitation facilities in the United States that contributed traumatic spinal cord injury data to the Uniform Data System for Medical Rehabilitation from January 2002 to December 2010. Variables analyzed included demographic information (age, sex, marital status, race/ethnicity, prehospital living setting, discharge setting), hospitalization information (length of stay, program interruptions, payer, onset date, rehabilitation impairment group, International Classification of Diseases 9 codes for admitting diagnosis, co-morbidities), and functional status (Functional Independence Measure [FIM] instrument ratings at admission and discharge, FIM efficiency, FIM gain). The final sample included 47,153 patients with traumatic spinal cord injury. Overall, the mean length of stay was 26.2 ± 23.2 days: yearly means ranged from 29.7 ± 25.4 in 2002 to 22.9 ± 18.9 in 2009. FIM total admission and discharge ratings also declined during the 8-yr study period; admission decreased from 60.5 ± 17.4 to 55.9 ± 16.3; discharge decreased from 86.1 ± 23.8 to 82.4 ± 23.4. Rehabilitation efficiency (FIM gain per day) remained relatively stable over time (1.6 ± 1.7 points per day). The percentage of all patients discharged to the community ranged from 75.8% to 71.5% per year. Wheelchair users stayed in rehabilitation longer than did persons who could walk (34.6 ± 217.4 vs. 17.4 ± 14.1 days) and also experienced less functional improvement (21.6 ± 15.8 vs. 29.6 ± 16.3 FIM points). National data from persons with traumatic spinal cord injury in 2002-2010 indicate that lengths of stay declined, but efficiency in functional independence was stable to slightly increased. More than 70% of patients were consistently discharged to community settings after inpatient rehabilitation.

Recovery of locomotion in the cat following spinal cord lesions.

PubMed

Rossignol, S; Bouyer, L; Barthélemy, D; Langlet, C; Leblond, H

2002-10-01

In most species, locomotor function beneath the level of a spinal cord lesion can be restored even if the cord is completely transected. This suggests that there is, within the spinal cord, an autonomous network of neurons capable of generating a locomotor pattern independently of supraspinal inputs. Recent studies suggest that several physiological and neurochemical changes have to occur in the neuronal networks located caudally to the lesion to allow the expression of spinal locomotion. Some evidence of this plasticity will be addressed in this review. In addition, original data on the functional organisation of the lumbar spinal cord will also be presented. Recent works in our lab show that segmental responsiveness of the spinal cord of the cat to locally micro-injected drugs in different lumbar segments, in combination with complete lesions at various level of the spinal cord, suggest a rostro-caudal organisation of spinal locomotor control. Moreover, the integrity of midlumbar segments seems to be crucial for the expression of spinal locomotion. These data suggest that the regions of critical importance for locomotion can be confined to a restricted portion of the spinal cord. Later, these midlumbar segments could be targeted by electrical stimulation or grafts to improve recovery of function. Understanding the changes in spinal cord neurophysiology and neurochemistry after a lesion is of critical importance to the improvement of treatments for locomotor rehabilitation in spinal-cord-injured patients.

Effect of Epsilon Aminocaproic Acid on Red-Cell Transfusion Requirements in Major Spinal Surgery

PubMed Central

Berenholtz, Sean M.; Pham, Julius Cuong; Garrett-Mayer, Elizabeth; Atchison, Christine W; Kostuik, John P.; Cohen, David B.; Nundy, Shantanu; Dorman, Todd; Ness, Paul M.; Klag, Michael J.; Pronovost, Peter J.; Kebaish, Khaled M.

2009-01-01

Study Design Randomized, placebo-controlled trial Objective To evaluate the efficacy of epsilon aminocaproic acid (EACA) to reduce the number of red-cell (RBC) transfusions in adult patients undergoing major spinal surgery. Summary of Background Data Reconstructive spinal surgery is associated with significant blood loss. The number of studies evaluating the efficacy of EACA in adult patients undergoing spinal surgery remains scarce and limited. Methods EACA (100 mg/kg) or placebo was administered to 182 adult patients after the induction of anesthesia followed by an infusion that was continued for 8 hours postoperatively. Primary end-points included total allogeneic RBC transfusions through postoperative day (POD) 8 and postoperative allogeneic plus autologus RBC transfusions through POD 8. Results Mean total allogeneic RBC transfusions were not statistically different between the groups (5.9 units EACA versus 6.9 units placebo; P=0.17). Mean postoperative RBC transfusions in the EACA group was less (2.0 units versus 2.8 units placebo; P=0.03). There was no significant difference in mean estimated intraoperative EBL (2938 cc EACA vs. 3273 cc placebo; P=0.32). Mean intensive care unit length of stay was decreased (EACA 1.8 days versus 2.8 days placebo; P=0.04). The incidence of thromboembolic complications was similar (2.2% EACA vs 6.6% placebo; P=0.15). Conclusions The difference in total allogeneic RBC transfusions between the groups was not statistically significant. EACA was associated with a 30% (0.8 units) reduction in postoperative RBC transfusions and a one-day reduction in ICU LOS, without an increased incidence of thromboembolic events. EACA may be considered for patients undergoing major spinal surgery. Larger studies are needed to evaluate the relationship between EACA and total RBC requirements. PMID:19730217

Effect of epsilon aminocaproic acid on red-cell transfusion requirements in major spinal surgery.

PubMed

Berenholtz, Sean M; Pham, Julius Cuong; Garrett-Mayer, Elizabeth; Atchison, Christine W; Kostuik, John P; Cohen, David B; Nundy, Shantanu; Dorman, Todd; Ness, Paul M; Klag, Michael J; Pronovost, Peter J; Kebaish, Khaled M

2009-09-01

: Randomized, placebo-controlled trial. : To evaluate the efficacy of epsilon aminocaproic acid (EACA) to reduce the number of red-cell (RBC) transfusions in adult patients undergoing major spinal surgery. : Reconstructive spinal surgery is associated with significant blood loss. The number of studies evaluating the efficacy of EACA in adult patients undergoing spinal surgery remains scarce and limited. : EACA (100 mg/kg) or placebo was administered to 182 adult patients after the induction of anesthesia followed by an infusion that was continued for 8 hours after surgery. Primary end points included total allogeneic RBC transfusions through postoperative day 8 and postoperative allogeneic plus autologus RBC transfusions through postoperative day 8. : Mean total allogeneic RBC transfusions were not statistically different between the groups (5.9 units EACA vs. 6.9 units placebo; P = 0.17). Mean postoperative RBC transfusions in the EACA group was less (2.0 units vs. 2.8 units placebo; P = 0.03). There was no significantdifference in mean estimated intraoperative estimated-blood loss (2938 cc EACA vs. 3273 cc placebo; P = 0.32). Mean intensive care unit length of stay was decreased (EACA: 1.8 days vs. 2.8 days placebo; P = 0.04). The incidence of thromboembolic complications was similar (2.2% EACA vs. 6.6% placebo; P = 0.15). : The difference in total allogeneic RBC transfusions between the groups was not statistically significant. EACA was associated with a 30% (0.8 units) reduction in postoperative RBC transfusions and a 1-day reduction in ICU LOS, without an increased incidence of thromboembolic events. EACA may be considered for patients undergoing major spinal surgery. Larger studies are needed to evaluate the relationship between EACA and total RBC requirements.

Use of quadrupedal step training to re-engage spinal interneuronal networks and improve locomotor function after spinal cord injury.

PubMed

Shah, Prithvi K; Garcia-Alias, Guillermo; Choe, Jaehoon; Gad, Parag; Gerasimenko, Yury; Tillakaratne, Niranjala; Zhong, Hui; Roy, Roland R; Edgerton, V Reggie

2013-11-01

Can lower limb motor function be improved after a spinal cord lesion by re-engaging functional activity of the upper limbs? We addressed this issue by training the forelimbs in conjunction with the hindlimbs after a thoracic spinal cord hemisection in adult rats. The spinal circuitries were more excitable, and behavioural and electrophysiological analyses showed improved hindlimb function when the forelimbs were engaged simultaneously with the hindlimbs during treadmill step-training as opposed to training only the hindlimbs. Neuronal retrograde labelling demonstrated a greater number of propriospinal labelled neurons above and below the thoracic lesion site in quadrupedally versus bipedally trained rats. The results provide strong evidence that actively engaging the forelimbs improves hindlimb function and that one likely mechanism underlying these effects is the reorganization and re-engagement of rostrocaudal spinal interneuronal networks. For the first time, we provide evidence that the spinal interneuronal networks linking the forelimbs and hindlimbs are amenable to a rehabilitation training paradigm. Identification of this phenomenon provides a strong rationale for proceeding toward preclinical studies for determining whether training paradigms involving upper arm training in concert with lower extremity training can enhance locomotor recovery after neurological damage.

Locomotor recovery after spinal cord hemisection/contusion injures in bonnet monkeys: footprint testing--a minireview.

PubMed

Rangasamy, Suresh Babu

2013-07-01

Spinal cord injuries usually produce loss or impairment of sensory, motor and reflex function below the level of damage. In the absence of functional regeneration or manipulations that promote regeneration, spontaneous improvements in motor functions occur due to the activation of multiple compensatory mechanisms in animals and humans following the partial spinal cord injury. Many studies were performed on quantitative evaluation of locomotor recovery after induced spinal cord injury in animals using behavioral tests and scoring techniques. Although few studies on rodents have led to clinical trials, it would appear imperative to use nonhuman primates such as macaque monkeys in order to relate the research outcomes to recovery of functions in humans. In this review, we will discuss some of our research evidences concerning the degree of spontaneous recovery in bipedal locomotor functions of bonnet monkeys that underwent spinal cord hemisection/contusion lesions. To our knowledge, this is the first report to discuss on the extent of spontaneous recovery in bipedal locomotion of macaque monkeys through the application of footprint analyzing technique. In addition, the results obtained were compared with the published data on recovery of quadrupedal locomotion of spinally injured rodents. We propose that the mechanisms underlying spontaneous recovery of functions in spinal cord lesioned monkeys may be correlated to the mature function of spinal pattern generator for locomotion under the impact of residual descending and afferent connections. Moreover, based on analysis of motor functions observed in locomotion in these subjected monkeys, we understand that spinal automatism and development of responses by afferent stimuli from outside the cord could possibly contribute to recovery of paralyzed hindlimbs. This report also emphasizes the functional contribution of progressive strengthening of undamaged nerve fibers through a collateral sprouts/synaptic plasticity formed in partially lesioned cord of monkeys. Copyright © 2013 Wiley Periodicals, Inc.

Cervical spine injury outcome--a review of 101 cases treated in a tertiary referral unit.

PubMed

Fielingsdorf, K; Dunn, R N

2007-03-01

Cervical spinal cord injury (SCI) is a devastating event for the patient and family. It has a huge impact on society because of the intensive resources required to manage the patient in both the acute and rehabilitation phases. Given the resource-limited setting in South Africa, questions are often raised regarding whether the outcome of this group of patients justifies the expense of their care. However local data have not been available to date. To evaluate the mortality, morbidity and functional outcome of cervical SCI patients in the South African environment. All cervical SCI patients managed in the acute spinal cord injury unit at Groote Schuur Hospital over a 12-month period were included. Epidemiological data, management, complications, neurological status and change were assessed. Those referred for rehabilitation were followed up in terms of mortality and ambulation status. There were 101 patients, with an average age of 34.7 years. Motor vehicle accidents were the commonest cause of injury, with violence contributing 21%. Fifty-nine patients required referral to a rehabilitation unit. Of these, 18 were functional walkers, and only 6 were care-dependent. By 1 year post injury all but 1 patient had been discharged from the health service. Fourteen patients died; in half of these cases injury was at C5 level and above. Despite cervical SCI being a devastating event, aggressive early intervention yields a better-than-expected 1-year survival rate. Associated problems, such as pressure sores, remain a major problem both for the patient and in terms of health care costs. It is difficult to predict prognosis on presentation because of spinal shock. It is recommended that all patients initially be treated aggressively, with exit strategies in place once all the information is available and a confident assessment of poor prognosis can be made.

Firing behavior of vestibular neurons during active and passive head movements: vestibulo-spinal and other non-eye-movement related neurons

NASA Technical Reports Server (NTRS)

McCrea, R. A.; Gdowski, G. T.; Boyle, R.; Belton, T.; Peterson, B. W. (Principal Investigator)

1999-01-01

The firing behavior of 51 non-eye movement related central vestibular neurons that were sensitive to passive head rotation in the plane of the horizontal semicircular canal was studied in three squirrel monkeys whose heads were free to move in the horizontal plane. Unit sensitivity to active head movements during spontaneous gaze saccades was compared with sensitivity to passive head rotation. Most units (29/35 tested) were activated at monosynaptic latencies following electrical stimulation of the ipsilateral vestibular nerve. Nine were vestibulo-spinal units that were antidromically activated following electrical stimulation of the ventromedial funiculi of the spinal cord at C1. All of the units were less sensitive to active head movements than to passive whole body rotation. In the majority of cells (37/51, 73%), including all nine identified vestibulo-spinal units, the vestibular signals related to active head movements were canceled. The remaining units (n = 14, 27%) were sensitive to active head movements, but their responses were attenuated by 20-75%. Most units were nearly as sensitive to passive head-on-trunk rotation as they were to whole body rotation; this suggests that vestibular signals related to active head movements were cancelled primarily by subtraction of a head movement efference copy signal. The sensitivity of most units to passive whole body rotation was unchanged during gaze saccades. A fundamental feature of sensory processing is the ability to distinguish between self-generated and externally induced sensory events. Our observations suggest that the distinction is made at an early stage of processing in the vestibular system.

Rho Inhibitor VX-210 in Acute Traumatic Subaxial Cervical Spinal Cord Injury: Design of the SPinal Cord Injury Rho INhibition InvestiGation (SPRING) Clinical Trial.

PubMed

Fehlings, Michael G; Kim, Kee D; Aarabi, Bizhan; Rizzo, Marco; Bond, Lisa M; McKerracher, Lisa; Vaccaro, Alexander R; Okonkwo, David O

2018-05-01

Traumatic spinal cord injury (SCI) is associated with a lifetime of disability stemming from loss of motor, sensory, and autonomic functions; these losses, along with increased comorbid sequelae, negatively impact health outcomes and quality of life. Early decompression surgery post-SCI can enhance patient outcomes, but does not directly facilitate neural repair and regeneration. Currently, there are no U.S. Food and Drug Administration-approved pharmacological therapies to augment motor function and functional recovery in individuals with traumatic SCI. After an SCI, the enzyme, Rho, is activated by growth-inhibitory factors and regulates events that culminate in collapse of the neuronal growth cone, failure of axonal regeneration, and, ultimately, failure of motor and functional recovery. Inhibition of Rho activation is a potential treatment for injuries such as traumatic SCI. VX-210, an investigational agent, inhibits Rho. When administered extradurally after decompression (corpectomy or laminectomy) and stabilization surgery in a phase 1/2a study, VX-210 was well tolerated. Here, we describe the design of the SPRING trial, a multicenter, phase 2b/3, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of VX-210 (NCT02669849). A subset of patients with acute traumatic cervical SCI is currently being enrolled in the United States and Canada. Medical, neurological, and functional changes are evaluated at 6 weeks and at 3, 6, and 12 months after VX-210 administration. Efficacy will be assessed by the primary outcome measure, change in upper extremity motor score at 6 months post-treatment, and by secondary outcomes that include question-based and task-based evaluations of functional recovery.

[Research progress in the role of aquaproin-4 and inward rectifying potassium channel 4.1 in spinal cord edema].

PubMed

Chen, Tiege; Dang, Yuexiu; Wang, Ming; Zhang, Dongliang; Guo, Yongqiang; Zhang, Haihong

2018-05-28

Spinal edema is a very important pathophysiological basis for secondary spinal cord injury, which affects the repair and prognosis of spinal cord injury. Aquaporin-4 is widely distributed in various organs of the body, and is highly expressed in the brain and spinal cord. Inward rectifying potassium channel 4.1 is a protein found in astrocytes of central nervous system. It interacts with aquaporins in function. Aquaporin-4 and inward rectifying potassium channel 4.1 play an important role in the formation and elimination of spinal cord edema, inhibition of glial scar formation and promotion of excitotoxic agents exclusion. The distribution and function of aquaporin-4 and inward rectifying potassium channel 4.1 in the central nervous system and their expression after spinal cord injury have multiple effects on spinal edema. Studies of aquaporin-4 and inward rectifying potassium channel 4.1 in the spinal cord may provide new ideas for the elimination and treatment of spinal edema.

Controlling specific locomotor behaviors through multidimensional monoaminergic modulation of spinal circuitries

PubMed Central

Musienko, Pavel; van den Brand, Rubia; Märzendorfer, Olivia; Roy, Roland R.; Gerasimenko, Yury; Edgerton, V. Reggie; Courtine, Grégoire

2012-01-01

Descending monoaminergic inputs markedly influence spinal locomotor circuits, but the functional relationships between specific receptors and the control of walking behavior remain poorly understood. To identify these interactions, we manipulated serotonergic, dopaminergic, and noradrenergic neural pathways pharmacologically during locomotion enabled by electrical spinal cord stimulation in adult spinal rats in vivo. Using advanced neurobiomechanical recordings and multidimensional statistical procedures, we reveal that each monoaminergic receptor modulates a broad but distinct spectrum of kinematic, kinetic and EMG characteristics, which we expressed into receptor–specific functional maps. We then exploited this catalogue of monoaminergic tuning functions to devise optimal pharmacological combinations to encourage locomotion in paralyzed rats. We found that, in most cases, receptor-specific modulatory influences summed near algebraically when stimulating multiple pathways concurrently. Capitalizing on these predictive interactions, we elaborated a multidimensional monoaminergic intervention that restored coordinated hindlimb locomotion with normal levels of weight bearing and partial equilibrium maintenance in spinal rats. These findings provide new perspectives on the functions of and interactions between spinal monoaminergic receptor systems in producing stepping, and define a framework to tailor pharmacotherapies for improving neurological functions after CNS disorders. PMID:21697376

Important Clinical Rehabilitation Principles Unique to People with Non-traumatic Spinal Cord Dysfunction.

PubMed

New, Peter Wayne; Eriks-Hoogland, Inge; Scivoletto, Giorgio; Reeves, Ronald K; Townson, Andrea; Marshall, Ruth; Rathore, Farooq A

2017-01-01

Background: Non-traumatic spinal cord dysfunction (SCDys) is caused by a large range of heterogeneous etiologies. Although most aspects of rehabilitation for traumatic spinal cord injury and SCDys are the same, people with SCDys have some unique rehabilitation issues. Purpose: This article presents an overview of important clinical rehabilitation principles unique to SCDys. Methods: Electronic literature search conducted (January 2017) using MEDLINE and Embase (1990-2016) databases for publications regarding SCDys. The focus of the literature search was on identifying publications that present suggestions regarding the clinical rehabilitation of SCDys. Results: The electronic search of MEDLINE and Embase identified no relevant publications, and the publications included were from the authors' libraries. A number of important clinical rehabilitation principles unique to people with SCDys were identified, including classification issues, general rehabilitation issues, etiology-specific issues, and a role for the rehabilitation physician as a diagnostic clinician. The classification issues were regarding the etiology of SCDys and the International Standards for Neurological Classification of Spinal Cord Injury. The general rehabilitation issues were predicting survival, improvement, and rehabilitation outcomes; admission to spinal rehabilitation units, including selection decision issues; participation in rehabilitation; and secondary health conditions. The etiology-specific issues were for SCDys due to spinal cord degeneration, tumors, and infections. Conclusions: Although there are special considerations regarding the rehabilitation of people with SCDys, such as the potential for progression of the underlying condition, functional improvement is typically significant with adequate planning of rehabilitation programs and special attention regarding the clinical condition of patients with SCDys.

Psychometric properties of the International Classification of Functioning, Disability and Health set for spinal cord injury nursing based on Rasch analysis.

PubMed

Li, Kun; Yan, Tiebin; You, Liming; Xie, Sumei; Li, Yun; Tang, Jie; Wang, Yingmin; Gao, Yan

2018-02-01

To examine the psychometric properties of the International Classification of Functioning, Disability and Health (ICF) set for spinal cord injury nursing (ICF-SCIN) using Rasch analysis. A total of 140 spinal cord injury patients were recruited between December 2013 and March 2014 through convenience sampling. Nurses used the components body functions (BF), body structures (BS), and activities and participation (AP) of the ICF-SCIN to rate the patients' functioning. Rasch analysis was performed using RUMM 2030 software. In each component, categories were rescored from 01234 to 01112 because of reversed thresholds. Nine testlets were created to overcome local dependency. Four categories which fit to the Rasch model poorly were deleted. After modification, the components BF, BS, and AP showed good fit to the Rasch model with a Bonferroni-adjusted significant level (χ 2  =   86.29, p = 0.006; χ 2  =   22.44, p = 0.130; χ 2  =   39.92, p = 0.159). The person separation indices (PSIs) for the three components were 0.80, 0.54, and 0.97, respectively. No differential item functioning (DIF) was detected across age, gender, or educational level. The fit properties of the ICF set were satisfactory after modifications. The ICF-SCIN has the potential as a nursing assessment instrument for measuring the functioning of patients with spinal cord injury. Implications for rehabilitation The International Classification of Functioning, Disability and Health (ICF) set for spinal cord injury nursing contains a group of categories which can reflect the functioning of spinal cord injury patients from the perspective of nurses. The components body functions (BF), body structures (BS), and activities and participation (AP) of the ICF set for spinal cord injury achieved the fit to the Rasch model through rescoring, generating testlets, and deleting categories with poor fit. The ICF set for spinal cord injury nursing (ICF-SCIN) has the potential to be used as a clinical nursing assessment tool in measuring the functioning of patients with spinal cord injury.

Predicting critical care unit-level complications after long-segment fusion procedures for adult spinal deformity.

PubMed

De la Garza-Ramos, Rafael; Nakhla, Jonathan; Gelfand, Yaroslav; Echt, Murray; Scoco, Aleka N; Kinon, Merritt D; Yassari, Reza

2018-03-01

To identify predictive factors for critical care unit-level complications (CCU complication) after long-segment fusion procedures for adult spinal deformity (ASD). The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database [2010-2014] was reviewed. Only adult patients who underwent fusion of 7 or more spinal levels for ASD were included. CCU complications included intraoperative arrest/infarction, ventilation >48 hours, pulmonary embolism, renal failure requiring dialysis, cardiac arrest, myocardial infarction, unplanned intubation, septic shock, stroke, coma, or new neurological deficit. A stepwise multivariate regression was used to identify independent predictors of CCU complications. Among 826 patients, the rate of CCU complications was 6.4%. On multivariate regression analysis, dependent functional status (P=0.004), combined approach (P=0.023), age (P=0.044), diabetes (P=0.048), and surgery for over 8 hours (P=0.080) were significantly associated with complication development. A simple scoring system was developed to predict complications with 0 points for patients aged <50, 1 point for patients between 50-70, 2 points for patients 70 or over, 1 point for diabetes, 2 points dependent functional status, 1 point for combined approach, and 1 point for surgery over 8 hours. The rate of CCU complications was 0.7%, 3.2%, 9.0%, and 12.6% for patients with 0, 1, 2, and 3+ points, respectively (P<0.001). The findings in this study suggest that older patients, patients with diabetes, patients who depend on others for activities of daily living, and patients who undergo combined approaches or surgery for over 8 hours may be at a significantly increased risk of developing a CCU-level complication after ASD surgery.

Transcranial cerebellar direct current stimulation and transcutaneous spinal cord direct current stimulation as innovative tools for neuroscientists

PubMed Central

Priori, Alberto; Ciocca, Matteo; Parazzini, Marta; Vergari, Maurizio; Ferrucci, Roberta

2014-01-01

Two neuromodulatory techniques based on applying direct current (DC) non-invasively through the skin, transcranial cerebellar direct current stimulation (tDCS) and transcutaneous spinal DCS, can induce prolonged functional changes consistent with a direct influence on the human cerebellum and spinal cord. In this article we review the major experimental works on cerebellar tDCS and on spinal tDCS, and their preliminary clinical applications. Cerebellar tDCS modulates cerebellar motor cortical inhibition, gait adaptation, motor behaviour, and cognition (learning, language, memory, attention). Spinal tDCS influences the ascending and descending spinal pathways, and spinal reflex excitability. In the anaesthetised mouse, DC stimulation applied under the skin along the entire spinal cord may affect GABAergic and glutamatergic systems. Preliminary clinical studies in patients with cerebellar disorders, and in animals and patients with spinal cord injuries, have reported beneficial effects. Overall the available data show that cerebellar tDCS and spinal tDCS are two novel approaches for inducing prolonged functional changes and neuroplasticity in the human cerebellum and spinal cord, and both are new tools for experimental and clinical neuroscientists. PMID:24907311

Neuromodulation of lower limb motor control in restorative neurology.

PubMed

Minassian, Karen; Hofstoetter, Ursula; Tansey, Keith; Mayr, Winfried

2012-06-01

One consequence of central nervous system injury or disease is the impairment of neural control of movement, resulting in spasticity and paralysis. To enhance recovery, restorative neurology procedures modify altered, yet preserved nervous system function. This review focuses on functional electrical stimulation (FES) and spinal cord stimulation (SCS) that utilize remaining capabilities of the distal apparatus of spinal cord, peripheral nerves and muscles in upper motor neuron dysfunctions. FES for the immediate generation of lower limb movement along with current rehabilitative techniques is reviewed. The potential of SCS for controlling spinal spasticity and enhancing lower limb function in multiple sclerosis and spinal cord injury is discussed. The necessity for precise electrode placement and appropriate stimulation parameter settings to achieve therapeutic specificity is elaborated. This will lead to our human work of epidural and transcutaneous stimulation targeting the lumbar spinal cord for enhancing motor functions in spinal cord injured people, supplemented by pertinent human research of other investigators. We conclude that the concept of restorative neurology recently received new appreciation by accumulated evidence for locomotor circuits residing in the human spinal cord. Technological and clinical advancements need to follow for a major impact on the functional recovery in individuals with severe damage to their motor system. Copyright © 2012 Elsevier B.V. All rights reserved.

Neuromodulation of lower limb motor control in restorative neurology

PubMed Central

Minassian, Karen; Hofstoetter, Ursula; Tansey, Keith; Mayr, Winfried

2012-01-01

One consequence of central nervous system injury or disease is the impairment of neural control of movement, resulting in spasticity and paralysis. To enhance recovery, restorative neurology procedures modify altered, yet preserved nervous system function. This review focuses on functional electrical stimulation (FES) and spinal cord stimulation (SCS) that utilize remaining capabilities of the distal apparatus of spinal cord, peripheral nerves and muscles in upper motor neuron dysfunctions. FES for the immediate generation of lower limb movement along with current rehabilitative techniques is reviewed. The potential of SCS for controlling spinal spasticity and enhancing lower limb function in multiple sclerosis and spinal cord injury is discussed. The necessity for precise electrode placement and appropriate stimulation parameter settings to achieve therapeutic specificity is elaborated. This will lead to our human work of epidural and transcutaneous stimulation targeting the lumbar spinal cord for enhancing motor functions in spinal cord injured people, supplemented by pertinent human research of other investigators. We conclude that the concept of restorative neurology recently received new appreciation by accumulated evidence for locomotor circuits residing in the human spinal cord. Technological and clinical advancements need to follow for a major impact on the functional recovery in individuals with severe damage to their motor system. PMID:22464657

The negotiated equilibrium model of spinal cord function.

PubMed

Wolpaw, Jonathan R

2018-04-16

The belief that the spinal cord is hardwired is no longer tenable. Like the rest of the CNS, the spinal cord changes during growth and aging, when new motor behaviours are acquired, and in response to trauma and disease. This paper describes a new model of spinal cord function that reconciles its recently appreciated plasticity with its long recognized reliability as the final common pathway for behaviour. According to this model, the substrate of each motor behaviour comprises brain and spinal plasticity: the plasticity in the brain induces and maintains the plasticity in the spinal cord. Each time a behaviour occurs, the spinal cord provides the brain with performance information that guides changes in the substrate of the behaviour. All the behaviours in the repertoire undergo this process concurrently; each repeatedly induces plasticity to preserve its key features despite the plasticity induced by other behaviours. The aggregate process is a negotiation among the behaviours: they negotiate the properties of the spinal neurons and synapses that they all use. The ongoing negotiation maintains the spinal cord in an equilibrium - a negotiated equilibrium - that serves all the behaviours. This new model of spinal cord function is supported by laboratory and clinical data, makes predictions borne out by experiment, and underlies a new approach to restoring function to people with neuromuscular disorders. Further studies are needed to test its generality, to determine whether it may apply to other CNS areas such as the cerebral cortex, and to develop its therapeutic implications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Using Mixed Methods to Build Research Capacity within the Spinal Cord Injured Population of New Zealand

ERIC Educational Resources Information Center

Sullivan, Martin; Derrett, Sarah; Paul, Charlotte; Beaver, Carolyn; Stace, Hilary

2014-01-01

In 2007, a 4-year longitudinal study of all people admitted to the two New Zealand spinal units commenced. It aims to (a) explore interrelationship(s) of body, self, and society for people with spinal cord injury (SCI) and (b) investigate how entitlement to rehabilitation and compensation through New Zealand's Accident Compensation Corporation…

Recovery of neuronal and network excitability after spinal cord injury and implications for spasticity

PubMed Central

D'Amico, Jessica M.; Condliffe, Elizabeth G.; Martins, Karen J. B.; Bennett, David J.; Gorassini, Monica A.

2014-01-01

The state of areflexia and muscle weakness that immediately follows a spinal cord injury (SCI) is gradually replaced by the recovery of neuronal and network excitability, leading to both improvements in residual motor function and the development of spasticity. In this review we summarize recent animal and human studies that describe how motoneurons and their activation by sensory pathways become hyperexcitable to compensate for the reduction of functional activation of the spinal cord and the eventual impact on the muscle. Specifically, decreases in the inhibitory control of sensory transmission and increases in intrinsic motoneuron excitability are described. We present the idea that replacing lost patterned activation of the spinal cord by activating synaptic inputs via assisted movements, pharmacology or electrical stimulation may help to recover lost spinal inhibition. This may lead to a reduction of uncontrolled activation of the spinal cord and thus, improve its controlled activation by synaptic inputs to ultimately normalize circuit function. Increasing the excitation of the spinal cord with spared descending and/or peripheral inputs by facilitating movement, instead of suppressing it pharmacologically, may provide the best avenue to improve residual motor function and manage spasticity after SCI. PMID:24860447

Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish

PubMed Central

Mokalled, Mayssa H.; Patra, Chinmoy; Dickson, Amy L.; Endo, Toyokazu; Stainier, Didier Y. R.; Poss, Kenneth D.

2016-01-01

Unlike mammals, zebrafish efficiently regenerate functional nervous system tissue after major spinal cord injury. Whereas glial scarring presents a roadblock for mammalian spinal cord repair, glial cells in zebrafish form a bridge across severed spinal cord tissue and facilitate regeneration, a relatively unexplored process. Here, we performed a genome-wide profiling screen for secreted factors that are upregulated during zebrafish spinal cord regeneration. We find that connective tissue growth factor a (ctgfa) is induced in and around glial cells that participate in initial bridging events. Mutations in ctgfa disrupt spinal cord repair, while transgenic ctgfa overexpression and local human CTGF recombinant protein delivery accelerate bridging and functional regeneration. Our study reveals that CTGF is necessary and sufficient to stimulate glial bridging and natural spinal cord regeneration. PMID:27811277

Kinematics of the thoracic T10-T11 motion segment: locus of instantaneous axes of rotation in flexion and extension.

PubMed

Qiu, Tian-Xia; Teo, Ee-Chon; Lee, Kim-Kheng; Ng, Hong-Wan; Yang, Kai

2004-04-01

The purpose of this study was to determine the locations and loci of instantaneous axes of rotation (IARs) of the T10-T11 motion segment in flexion and extension. An anatomically accurate three-dimensional model of thoracic T10-T11 functional spinal unit (FSU) was developed and validated against published experimental data under flexion, extension, lateral bending, and axial rotation loading configurations. The validated model was exercised under six load configurations that produced motions only in the sagittal plane to characterize the loci of IARs for flexion and extension. The IARs for both flexion and extension under these six load types were directly below the geometric center of the moving vertebra, and all the loci of IARs were tracked superoanteriorly for flexion and inferoposteriorly for extension with rotation. These findings may offer an insight to better understanding of the kinematics of the human thoracic spine and provide clinically relevant information for the evaluation of spinal stability and implant device functionality.

Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on Functional Recovery after Spinal Cord Injury

DTIC Science & Technology

2014-10-01

atrophy. Interestingly, there is a clinical phenomenon that stretching can lead to muscle fiber hypertrophy , but that doesn’t appear to be...specific muscle groups) on functional recovery after spinal cord injury in a rat model. We have undertaken these studies because of an observation we...spinal cord injury, locomotor recovery, physical therapy, muscle stretch, joint range- of-motion, rat. Overall Project Summary: In this, the

Combined Effects of Acrobatic Exercise and Magnetic Stimulation on the Functional Recovery after Spinal Cord Lesions

PubMed Central

Wieraszko, Andrzej

2008-01-01

Abstract The objective of the study was to determine whether physical exercise combined with epidural spinal cord magnetic stimulation could improve recovery after injury of the spinal cord. Spinal cord lesioning in mice resulted in reduced locomotor function and negatively affected the muscle strength tested in vitro. Acrobatic exercise attenuated the behavioral effects of spinal cord injury. The exposure to magnetic fields facilitated further this improvement. The progress in behavioral recovery was correlated with reduced muscle degeneration and enhanced muscle contraction. The acrobatic exercise combined with stimulation with magnetic fields significantly facilitates behavioral recovery and muscle physiology in mice following spinal cord injury. PMID:18986227

Update on traumatic acute spinal cord injury. Part 2.

PubMed

Mourelo Fariña, M; Salvador de la Barrera, S; Montoto Marqués, A; Ferreiro Velasco, M E; Galeiras Vázquez, R

The aim of treatment in acute traumatic spinal cord injury is to preserve residual neurologic function, avoid secondary injury, and restore spinal alignment and stability. In this second part of the review, we describe the management of spinal cord injury focusing on issues related to short-term respiratory management, where the preservation of diaphragmatic function is a priority, with prediction of the duration of mechanical ventilation and the need for tracheostomy. Surgical assessment of spinal injuries based on updated criteria is discussed, taking into account that although the type of intervention depends on the surgical team, nowadays treatment should afford early spinal decompression and stabilization. Within a comprehensive strategy in spinal cord injury, it is essential to identify and properly treat patient anxiety and pain associated to spinal cord injury, as well as to prevent and ensure the early diagnosis of complications secondary to spinal cord injury (thromboembolic disease, gastrointestinal and urinary disorders, pressure ulcers). Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Assessment of effectiveness of percutaneous adhesiolysis in managing chronic low back pain secondary to lumbar central spinal canal stenosis.

PubMed

Manchikanti, Laxmaiah; Cash, Kimberly A; McManus, Carla D; Pampati, Vidyasagar

2013-01-01

Chronic persistent low back and lower extremity pain secondary to central spinal stenosis is common and disabling. Lumbar surgical interventions with decompression or fusion are most commonly performed to manage severe spinal stenosis. However, epidural injections are also frequently performed in managing central spinal stenosis. After failure of epidural steroid injections, the next sequential step is percutaneous adhesiolysis and hypertonic saline neurolysis with a targeted delivery. The literature on the effectiveness of percutaneous adhesiolysis in managing central spinal stenosis after failure of epidural injections has not been widely studied. A prospective evaluation. An interventional pain management practice, a specialty referral center, a private practice setting in the United States. To evaluate the effectiveness of percutaneous epidural adhesiolysis in patients with chronic low back and lower extremity pain with lumbar central spinal stenosis. Seventy patients were recruited. The initial phase of the study was randomized, double-blind with a comparison of percutaneous adhesiolysis with caudal epidural injections. The 25 patients from the adhesiolysis group continued with follow-up, along with 45 additional patients, leading to a total of 70 patients. All patients received percutaneous adhesiolysis and appropriate placement of the Racz catheter, followed by an injection of 5 mL of 2% preservative-free lidocaine with subsequent monitoring in the recovery room. In the recovery room, each patient also received 6 mL of 10% hypertonic sodium chloride solution, and 6 mg of non-particulate betamethasone, followed by an injection of 1 mL of sodium chloride solution and removal of the catheter. Multiple outcome measures were utilized including the Numeric Rating Scale (NRS), the Oswestry Disability Index 2.0 (ODI), employment status, and opioid intake with assessment at 3, 6, and 12, 18 and 24 months post treatment. The primary outcome measure was 50% or more improvement in pain scores and ODI scores. Overall, a primary outcome or significant pain relief and functional status improvement of 50% or more was seen in 71% of patients at the end of 2 years. The overall number of procedures over a period of 2 years were 5.7 ± 2.73. The lack of a control group and a prospective design. Significant relief and functional status improvement as seen in 71% of the 70 patients with percutaneous adhesiolysis utilizing local anesthetic steroids and hypertonic sodium chloride solution may be an effective management strategy in patients with chronic function limiting low back and lower extremity pain with central spinal stenosis after failure of conservatie management and fluoroscopically directed epidural injections.

Multiple sclerosis lesions affect intrinsic functional connectivity of the spinal cord.

PubMed

Conrad, Benjamin N; Barry, Robert L; Rogers, Baxter P; Maki, Satoshi; Mishra, Arabinda; Thukral, Saakshi; Sriram, Subramaniam; Bhatia, Aashim; Pawate, Siddharama; Gore, John C; Smith, Seth A

2018-06-01

Patients with multiple sclerosis present with focal lesions throughout the spinal cord. There is a clinical need for non-invasive measurements of spinal cord activity and functional organization in multiple sclerosis, given the cord's critical role in the disease. Recent reports of spontaneous blood oxygenation level-dependent fluctuations in the spinal cord using functional MRI suggest that, like the brain, cord activity at rest is organized into distinct, synchronized functional networks among grey matter regions, likely related to motor and sensory systems. Previous studies looking at stimulus-evoked activity in the spinal cord of patients with multiple sclerosis have demonstrated increased levels of activation as well as a more bilateral distribution of activity compared to controls. Functional connectivity studies of brain networks in multiple sclerosis have revealed widespread alterations, which may take on a dynamic trajectory over the course of the disease, with compensatory increases in connectivity followed by decreases associated with structural damage. We build upon this literature by examining functional connectivity in the spinal cord of patients with multiple sclerosis. Using ultra-high field 7 T imaging along with processing strategies for robust spinal cord functional MRI and lesion identification, the present study assessed functional connectivity within cervical cord grey matter of patients with relapsing-remitting multiple sclerosis (n = 22) compared to a large sample of healthy controls (n = 56). Patient anatomical images were rated for lesions by three independent raters, with consensus ratings revealing 19 of 22 patients presented with lesions somewhere in the imaged volume. Linear mixed models were used to assess effects of lesion location on functional connectivity. Analysis in control subjects demonstrated a robust pattern of connectivity among ventral grey matter regions as well as a distinct network among dorsal regions. A gender effect was also observed in controls whereby females demonstrated higher ventral network connectivity. Wilcoxon rank-sum tests detected no differences in average connectivity or power of low frequency fluctuations in patients compared to controls. The presence of lesions was, however, associated with local alterations in connectivity with differential effects depending on columnar location. The patient results suggest that spinal cord functional networks are generally intact in relapsing-remitting multiple sclerosis but that lesions are associated with focal abnormalities in intrinsic connectivity. These findings are discussed in light of the current literature on spinal cord functional MRI and the potential neurological underpinnings.

Visceral responses to spinal manipulation.

PubMed

Bolton, Philip S; Budgell, Brian

2012-10-01

While spinal manipulation is widely seen as a reasonable treatment option for biomechanical disorders of the spine, such as neck pain and low back pain, the use of spinal manipulation to treat non-musculoskeletal complaints remains controversial. This controversy is due in part to the perception that there is no robust neurobiological rationale to justify using a biomechanical treatment of the spine to address a disorder of visceral function. This paper therefore looks at the physiological evidence that spinal manipulation can impact visceral function. A structured search was conducted, using PubMed and the Index to Chiropractic Literature, to construct of corpus of primary data studies in healthy human subjects of the effects of spinal manipulation on visceral function. The corpus of literature is not large, and the greatest number of papers concerns cardiovascular function. Authors often attribute visceral effects of spinal manipulation to somato-autonomic reflexes. While this is not unreasonable, little attention is paid to alternative mechanisms such as somato-humoural pathways. Thus, while the literature confirms that mechanical stimulation of the spine modulates some organ functions in some cohorts, a comprehensive neurobiological rationale for this general phenomenon has yet to appear. Copyright © 2012 Elsevier Ltd. All rights reserved.

Compensatory axon sprouting for very slow axonal die-back in a transgenic model of spinal muscular atrophy type III.

PubMed

Udina, Esther; Putman, Charles T; Harris, Luke R; Tyreman, Neil; Cook, Victoria E; Gordon, Tessa

2017-03-01

Smn +/- transgenic mouse is a model of the mildest form of spinal muscular atrophy. Although there is a loss of spinal motoneurons in 11-month-old animals, muscular force is maintained. This maintained muscular force is mediated by reinnervation of the denervated fibres by surviving motoneurons. The spinal motoneurons in these animals do not show an increased susceptibility to death after nerve injury and they retain their regenerative capacity. We conclude that the hypothesized immaturity of the neuromuscular system in this model cannot explain the loss of motoneurons by systematic die-back. Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans and is the leading genetic cause of infantile death. Patients lack the SMN1 gene with the severity of the disease depending on the number of copies of the highly homologous SMN2 gene. Although motoneuron death in the Smn +/- transgenic mouse model of the mildest form of SMA, SMA type III, has been reported, we have used retrograde tracing of sciatic and femoral motoneurons in the hindlimb with recording of muscle and motor unit isometric forces to count the number of motoneurons with intact neuromuscular connections. Thereby, we investigated whether incomplete maturation of the neuromuscular system induced by survival motoneuron protein (SMN) defects is responsible for die-back of axons relative to survival of motoneurons. First, a reduction of ∼30% of backlabelled motoneurons began relatively late, at 11 months of age, with a significant loss of 19% at 7 months. Motor axon die-back was affirmed by motor unit number estimation. Loss of functional motor units was fully compensated by axonal sprouting to retain normal contractile force in four hindlimb muscles (three fast-twitch and one slow-twitch) innervated by branches of the sciatic nerve. Second, our evaluation of whether axotomy of motoneurons in the adult Smn +/- transgenic mouse increases their susceptibility to cell death demonstrated that all the motoneurons survived and they sustained their capacity to regenerate their nerve fibres. It is concluded the systematic die-back of motoneurons that innervate both fast- and slow-twitch muscle fibres is not related to immaturity of the neuromuscular system in SMA. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

International spinal cord injury cardiovascular function basic data set.

PubMed

Krassioukov, A; Alexander, M S; Karlsson, A-K; Donovan, W; Mathias, C J; Biering-Sørensen, F

2010-08-01

To create an International Spinal Cord Injury (SCI) Cardiovascular Function Basic Data Set within the framework of the International SCI Data Sets. An international working group. The draft of the data set was developed by a working group comprising members appointed by the American Spinal Injury Association (ASIA), the International Spinal Cord Society (ISCoS) and a representative of the executive committee of the International SCI Standards and Data Sets. The final version of the data set was developed after review by members of the executive committee of the International SCI Standards and Data Sets, the ISCoS scientific committee, ASIA board, relevant and interested international organizations and societies, individual persons with specific interest and the ISCoS Council. To make the data set uniform, each variable and each response category within each variable have been specifically defined in a way that is designed to promote the collection and reporting of comparable minimal data. The variables included in the International SCI Cardiovascular Function Basic Data Set include the following items: date of data collection, cardiovascular history before the spinal cord lesion, events related to cardiovascular function after the spinal cord lesion, cardiovascular function after the spinal cord lesion, medications affecting cardiovascular function on the day of examination; and objective measures of cardiovascular functions, including time of examination, position of examination, pulse and blood pressure. The complete instructions for data collection and the data sheet itself are freely available on the websites of both ISCoS (http://www.iscos.org.uk) and ASIA (http://www.asia-spinalinjury.org).

Spinal microcircuits comprising dI3 interneurons are necessary for motor functional recovery following spinal cord transection

PubMed Central

Bui, Tuan V; Stifani, Nicolas; Akay, Turgay; Brownstone, Robert M

2016-01-01

The spinal cord has the capacity to coordinate motor activities such as locomotion. Following spinal transection, functional activity can be regained, to a degree, following motor training. To identify microcircuits involved in this recovery, we studied a population of mouse spinal interneurons known to receive direct afferent inputs and project to intermediate and ventral regions of the spinal cord. We demonstrate that while dI3 interneurons are not necessary for normal locomotor activity, locomotor circuits rhythmically inhibit them and dI3 interneurons can activate these circuits. Removing dI3 interneurons from spinal microcircuits by eliminating their synaptic transmission left locomotion more or less unchanged, but abolished functional recovery, indicating that dI3 interneurons are a necessary cellular substrate for motor system plasticity following transection. We suggest that dI3 interneurons compare inputs from locomotor circuits with sensory afferent inputs to compute sensory prediction errors that then modify locomotor circuits to effect motor recovery. DOI: http://dx.doi.org/10.7554/eLife.21715.001 PMID:27977000

Effect of electrical stimulation on neural regeneration via the p38-RhoA and ERK1/2-Bcl-2 pathways in spinal cord-injured rats

PubMed Central

Joo, Min Cheol; Jang, Chul Hwan; Park, Jong Tae; Choi, Seung Won; Ro, Seungil; Kim, Min Seob; Lee, Moon Young

2018-01-01

Although electrical stimulation is therapeutically applied for neural regeneration in patients, it remains unclear how electrical stimulation exerts its effects at the molecular level on spinal cord injury (SCI). To identify the signaling pathway involved in electrical stimulation improving the function of injured spinal cord, 21 female Sprague-Dawley rats were randomly assigned to three groups: control (no surgical intervention, n = 6), SCI (SCI only, n = 5), and electrical simulation (ES; SCI induction followed by ES treatment, n = 10). A complete spinal cord transection was performed at the 10th thoracic level. Electrical stimulation of the injured spinal cord region was applied for 4 hours per day for 7 days. On days 2 and 7 post SCI, the Touch-Test Sensory Evaluators and the Basso-Beattie-Bresnahan locomotor scale were used to evaluate rat sensory and motor function. Somatosensory-evoked potentials of the tibial nerve of a hind paw of the rat were measured to evaluate the electrophysiological function of injured spinal cord. Western blot analysis was performed to measure p38-RhoA and ERK1/2-Bcl-2 pathways related protein levels in the injured spinal cord. Rat sensory and motor functions were similar between SCI and ES groups. Compared with the SCI group, in the ES group, the latencies of the somatosensory-evoked potential of the tibial nerve of rats were significantly shortened, the amplitudes were significantly increased, RhoA protein level was significantly decreased, protein gene product 9.5 expression, ERK1/2, p38, and Bcl-2 protein levels in the spinal cord were significantly increased. These data suggest that ES can promote the recovery of electrophysiological function of the injured spinal cord through regulating p38-RhoA and ERK1/2-Bcl-2 pathway-related protein levels in the injured spinal cord. PMID:29557386

The Uniform Data System for Medical Rehabilitation Report of Patients with Traumatic Spinal Cord Injury Discharged from Rehabilitation Programs in 2002 – 2010

PubMed Central

Granger, Carl V.; Karmarkar, Amol M.; Graham, James E.; Deutsch, Anne; Niewczyk, Paulette; DiVita, Margaret A.; Ottenbacher, Kenneth J.

2012-01-01

Objective Provide benchmarking information from a large national sample of patients receiving inpatient rehabilitation following a traumatic spinal cord injury. Design Analysis of secondary data from 891 inpatient medical rehabilitation facilities in the United States that contributed traumatic spinal cord injury data to the Uniform Data System for Medical Rehabilitation (UDSmr) during the period January 2002 through December 2010. Variables analyzed included demographic information (age, sex, marital status, race/ethnicity, pre-hospital living setting, discharge setting), hospitalization information (length of stay, program interruptions, payer, onset date, rehabilitation impairment group, ICD-9 codes for admitting diagnosis, comorbidities), and functional status (FIM® instrument [“FIM”] ratings at admission and discharge, FIM efficiency, FIM gain). Results The final sample included 47,153 patients with traumatic spinal cord injury. Overall mean length of stay = 26.2 (±23.2) days: yearly means ranged from 29.7 (±25.4) in 2002 to 22.9 (±18.9) in 2009. FIM total admission and discharge ratings also declined over the 8-year study period: admission decreased from 60.5 (± 17.4) to 55.9 (±16.3); discharge decreased from 86.1 (±23.8) to 82.4 (±23.4). Rehabilitation efficiency (FIM gain per day) remained relatively stable over time (1.6 ±1.7 points per day). The percentage of all patients discharged to the community ranged from 75.8% to 71.5% per year. Wheelchair users stayed in rehabilitation longer than persons who could walk (34.6 ±217.4 vs. 17.4 ±14.1 days) and also experienced less functional improvement (21.6 ±15.8 vs. 29.6 ±16.3 FIM points). Conclusions National data from persons with traumatic spinal cord injury in 2002-2010 indicate that lengths of stay declined, but efficiency in functional independence was stable to slightly increased. Over seventy percent of patients were consistently discharged to community settings following inpatient rehabilitation. PMID:22407160

Spinal Motocross Injuries in the United Kingdom.

PubMed

Singh, Rohit; Bhalla, Amit; Ockendon, Matthew; Hay, Stuart

2018-01-01

Motocross is a form of motorcycle racing held on established off-road circuits and has been a recreational and competitive sport across the world for >100 years. In the United Kingdom alone, motocross has grown into a phenomenally ambitious and popular franchise. There are >200 motocross clubs across the country, permitting >900 events annually. To assess the current trend of spine-related motocross injuries over the past 5 years. Descriptive epidemiology study. Data were prospectively collected over 5 years (August 2010-August 2015) at our regional trauma and spine unit, regardless of whether the rider was performing the sport competitively or recreationally. During the study period, spine-related injuries were identified for 174 patients (age range, 6-75 years) who were directly referred to our department following recreational or competitive motocross, with most injuries being sustained within the early spring and summer months, representing the start of the motocross season. A significant number of injuries were in males (n = 203, 94%), with the majority of injuries occurring within the 21- to 30-year-old age group. A total of 116 (54%) injuries required operative treatment. The most common spinal injury was thoracolumbar burst fracture (n = 95), followed by chance fractures (n = 26). This data series emphasizes the prevalence and devastation of motocross-related spinal injuries in the United Kingdom and may serve in administering sanctions and guidelines to governing bodies of motocross. The spinal injuries that occur during motocross have significant capital connotations for regional spinal centers. The recent surge in motocross popularity is correlated with the number of injuries, which have increased over the past 5 years by almost 500%.

The human cerebellum: a review of physiologic neuroanatomy.

PubMed

Roostaei, Tina; Nazeri, Arash; Sahraian, Mohammad Ali; Minagar, Alireza

2014-11-01

The cerebellum resides in the posterior cranial fossa dorsal to the brainstem and has diverse connections to the cerebrum, brain stem, and spinal cord. It is anatomically and physiologically divided into distinct functional compartments and is composed of highly regular arrays of neuronal units, each sharing the same basic cerebellar microcircuitry. Its circuitry is critically involved in motor control and motor learning, and its role in nonmotor cognitive and affective functions is becoming increasingly recognized. This article describes the cerebellar gross and histologic neuroanatomy in relation to its function, and the relevance of cerebellar circuitry and firing patterns to motor learning. Copyright © 2014 Elsevier Inc. All rights reserved.

Intensive care unit versus hospital floor: a comparative study of postoperative management of patients with adolescent idiopathic scoliosis.

PubMed

Shan, Le-Qun; Skaggs, David L; Lee, Christopher; Kissinger, Catherine; Myung, Karen S

2013-04-03

Patients undergoing posterior spinal instrumentation and fusion surgery for adolescent idiopathic scoliosis were admitted to the intensive care unit until two years ago, at which time we changed our protocol to admit these patients to the general hospital floor following a brief stay in a postanesthesia care unit. This study compared postoperative management on a hospital floor with that in the intensive care unit for patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion. A retrospective review of 124 consecutive patients with adolescent idiopathic scoliosis treated with spinal fusion from August 2007 to August 2010 was performed. Inclusion criteria were a diagnosis of adolescent idiopathic scoliosis and posterior spinal instrumentation and fusion surgery. Of 124 patients, sixty-six were managed postoperatively in the intensive care unit and fifty-eight, on the hospital floor. The mean age at the time of surgery was fourteen years. A mean of eleven vertebral levels (range, six to fifteen levels) were fused. No significant difference between the groups was found with respect to the mean age at the time of surgery, mean weight, mean preoperative and postoperative Cobb angles, and mean number of levels fused (p ≥ 0.12). However, the use of analgesic and antianxiety medication, number of postoperative blood tests, days of hospital stay, and number of physical therapy sessions were significantly decreased in the floor group compared with the intensive care unit group (p ≤ 0.05). No patient from the floor group had to be admitted to the intensive care unit. The mean charge was $33,121 for the floor group and $39,252 for the intensive care unit group (p < 0.001). Initial postoperative management of patients with adolescent idiopathic scoliosis following a posterior spinal instrumentation and fusion surgery on a general hospital floor, rather than in an intensive care unit, was associated with a shorter hospital stay, fewer blood tests, less analgesic and antianxiety medication usage, and fewer physical therapy sessions at this high-volume, academic, tertiary-care children's hospital. In addition to improved patient outcomes, there was a significant decrease of 16% in hospital charges for the group that did not go to the intensive care unit.

Spinal cord injuries functional rehabilitation - Traditional approaches and new strategies in physiotherapy.

PubMed

de Almeida, Patrícia Maria Duarte

2006-02-01

Considering the body structures and systems loss of function, after a Spinal Cord Injury, with is respective activities limitations and social participation restriction, the rehabilitation process goals are to achieve the maximal functional independence and quality of life allowed by the clinical lesion. For this is necessary a rehabilitation period with a rehabilitation team, including the physiotherapist whose interventions will depend on factors such degree of completeness or incompleteness and patient clinical stage. Physiotherapy approach includes several procedures and techniques related with a traditional model or with the recent perspective of neuronal regeneration. Following a traditional model, the interventions in complete A and incomplete B lesions, is based on compensatory method of functional rehabilitation using the non affected muscles. In the incomplete C and D lesions, motor re-education below the lesion, using key points to facilitate normal and selective patterns of movement is preferable. In other way if the neuronal regeneration is possible with respective function improve; the physiotherapy approach goals are to maintain muscular trofism and improve the recruitment of motor units using intensive techniques. In both, there is no scientific evidence to support the procedures, exists a lack of investigation and most of the research are methodologically poor. © 2006 Sociedade Portuguesa de Pneumologia/SPP.

Measurement of occlusion of the spinal canal and intervertebral foramen by intervertebral disc bulge

PubMed Central

Cuchanski, Mathieu; Cook, Daniel; Whiting, Donald M.; Cheng, Boyle C.

2011-01-01

Background Disc protrusion has been proposed to be a possible cause of both pain and stenosis in the lower spine. No previous study has described the amount of disc occlusion of the spinal canal and intervertebral foramen that occurs under different loading conditions. The objective of this study was to quantitatively assess the percent occlusion of the spinal canal and intervertebral foramen by disc bulge under different loading conditions. Methods Spinal canal depth and foraminal width were measured on computed tomography–scanned images of 7 human lumbar spine specimens. In vitro disc bulge measurements were completed by use of a previously described method in which single functional spinal units were subjected to 3 separate load protocols in a spine test machine and disc bulge was recorded with an optoelectric motion system that tracked active light-emitting diodes placed on the posterior and posterolateral aspects of the intervertebral disc. Occlusion was defined as percentage of encroachment into area of interest by maximum measured disc bulge at corresponding point of interest (the spinal canal is at the posterior point; the intervertebral foramen is at the posterolateral point). Results The mean spinal canal depth and mean foraminal width were 19 4 ± mm and 5 ± 2 mm, respectively. Mean spinal canal occlusion under a 250-N axial load, ± 2.5 Nm of flexion/extension, and ± 2.5 Nm of lateral bend was 2.5% ± 1.9%, 2.5% ± 1.6%, and 1.5% ± 0.8%, respectively. Mean intervertebral foramen occlusion under a 250-N axial load, ± 2.5 Nm of flexion/extension, and ± 2.5 Nm of lateral bend was 7.8% ± 4.7%, 9.5% ± 5.7%, and 11.3% ± 6.2%, respectively. Conclusion Percent occlusion of the spinal canal and intervertebral foramen is dependent on magnitude and direction of load. Exiting neural elements at the location of the intervertebral foramen are the most vulnerable to impingement and generation of pain. PMID:25802663

Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-14-2-0132 TITLE: Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury...per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and...COVERED 29 Sep 2015 - 28 Sep 2016 4. TITLE AND SUBTITLE Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal

Changes in Afferent Activity After Spinal Cord Injury

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2010-01-01

Aims To summarize the changes that occur in the properties of bladder afferent neurons following spinal cord injury. Methods Literature review of anatomical, immunohistochemical, and pharmacologic studies of normal and dysfunctional bladder afferent pathways. Results Studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through coordination centers (periaqueductal gray and pontine micturition center) located in the rostral brain stem. This reflex pathway, which is activated by small myelinated (Aδ) bladder afferent nerves, is in turn modulated by higher centers in the cerebral cortex involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary voiding, as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury, the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. The recovery of bladder function after spinal cord injury is dependent in part on the plasticity of bladder afferent pathways and the unmasking of reflexes triggered by unmyelinated, capsaicin-sensitive, C-fiber bladder afferent neurons. Plasticity is associated with morphologic, chemical, and electrical changes in bladder afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and the peripheral target organs. Conclusions Spinal cord injury at sites remote from the lumbosacral spinal cord can indirectly influence properties of bladder afferent neurons by altering the function and chemical environment in the bladder or the spinal cord. PMID:20025033

A THREE-DIMENSIONAL MAP OF THE HINDLIMB MOTOR REPRESENTATION IN THE LUMBAR SPINAL CORD IN SPRAGUE DAWLEY RATS

PubMed Central

Borrell, Jordan A.; Frost, Shawn; Peterson, Jeremy; Nudo, Randolph J.

2016-01-01

Objective Spinal cord injury (SCI) is a devastating neurological trauma with a prevalence of about 282,000 people living with an SCI in the United States in 2016. Advances in neuromodulatory devices hold promise for restoring function by incorporating the delivery of electrical current directly into the spinal cord grey matter via intraspinal microstimulation (ISMS). In such designs, detailed topographic maps of spinal cord outputs are needed to determine ISMS locations for eliciting hindlimb movements. The primary goal of the present study was to derive a topographic map of functional motor outputs in the lumbar spinal cord to hindlimb skeletal muscles as defined by ISMS in a rat model. Approach Experiments were carried out in nine healthy, adult, male, Sprague Dawley rats. After a laminectomy of the T13-L1 vertebrae and removal of the dura mater, a four-shank, 16-channel microelectrode array was inserted along a three-dimensional (200 µm) stimulation grid. Trains of three biphasic current pulses were used to determine evoked movements and EMG activity. Via fine wire electromyographic (EMG) electrodes, Stimulus-Triggered Averaging (StTA) was used on rectified EMG data to determine response latency. Main results Hindlimb movements were elicited at a median current intensity of 6 µA, and thresholds were significantly lower in ventrolateral sites. Movements typically consisted of whole leg, hip, knee, ankle, toe, and trunk movements. Hip movements dominated rostral to the T13 vertebral segment, knee movements were evoked at the T13-L1 vertebral junction, while ankle and digit movements were found near the rostral L1 vertebra. Whole leg movements spanned the entire rostrocaudal region explored, while trunk movements dominated medially. StTAs of EMG activity demonstrated a latency of ~4 ms. Significance The derived motor map provides insight into the parameters needed for future neuromodulatory devices. PMID:27934789

A 3D map of the hindlimb motor representation in the lumbar spinal cord in Sprague Dawley rats

NASA Astrophysics Data System (ADS)

Borrell, Jordan A.; Frost, Shawn B.; Peterson, Jeremy; Nudo, Randolph J.

2017-02-01

Objective. Spinal cord injury (SCI) is a devastating neurological trauma with a prevalence of about 282 000 people living with an SCI in the United States in 2016. Advances in neuromodulatory devices hold promise for restoring function by incorporating the delivery of electrical current directly into the spinal cord grey matter via intraspinal microstimulation (ISMS). In such designs, detailed topographic maps of spinal cord outputs are needed to determine ISMS locations for eliciting hindlimb movements. The primary goal of the present study was to derive a topographic map of functional motor outputs in the lumbar spinal cord to hindlimb skeletal muscles as defined by ISMS in a rat model. Approach. Experiments were carried out in nine healthy, adult, male, Sprague Dawley rats. After a laminectomy of the T13-L1 vertebrae and removal of the dura mater, a four-shank, 16-channel microelectrode array was inserted along a 3D (200 µm) stimulation grid. Trains of three biphasic current pulses were used to determine evoked movements and electromyographic (EMG) activity. Via fine wire EMG electrodes, stimulus-triggered averaging (StTA) was used on rectified EMG data to determine response latency. Main results. Hindlimb movements were elicited at a median current intensity of 6 µA, and thresholds were significantly lower in ventrolateral sites. Movements typically consisted of whole leg, hip, knee, ankle, toe, and trunk movements. Hip movements dominated rostral to the T13 vertebral segment, knee movements were evoked at the T13-L1 vertebral junction, while ankle and digit movements were found near the rostral L1 vertebra. Whole leg movements spanned the entire rostrocaudal region explored, while trunk movements dominated medially. StTAs of EMG activity demonstrated a latency of ~4 ms. Significance. The derived motor map provides insight into the parameters needed for future neuromodulatory devices.

The triple monoamine re-uptake inhibitor DOV 216,303 promotes functional recovery after spinal cord contusion injury in mice.

PubMed

Chu, Tak-Ho; Cummins, Karen; Stys, Peter K

2018-05-14

Serotonin, noradrenaline and dopamine are important neuromodulators for locomotion in the spinal cord. Disruption of descending axons after spinal cord injury resulted in reduction of excitatory and neuromodulatory inputs to spinal neurons for locomotion. Receptor agonists or reuptake inhibitors for these neuromodulators have been shown to be beneficial in incomplete spinal cord injury. In this study, we tested a triple re-uptake inhibitor, DOV 216,303, for its ability to affect motor function recovery after spinal cord injury in mice. We impacted C57 mouse spinal cord at the T11 vertebral level and administered vehicle or DOV 216,303 at 10 mg/kg, b.i.d via intraperitoneal injections for 7 days. We monitored motor function with the Basso Mouse Scale for locomotion for 4 weeks. Spinal cords were harvested and histological examinations were performed to assess tissue sparing and lesion severity. Results showed that DOV 216,303-treated mice recovered significantly better than vehicle treated mice starting at 14 days post injury until the end of the survival period. Lesion size of the DOV 216,303 treated mice was also smaller compared to that of vehicle treated mice. This study suggests DOV 216,303 as a potential therapeutic after spinal cord injury warrants further investigation. Copyright © 2018 Elsevier B.V. All rights reserved.

The change tendency of PI3K/Akt pathway after spinal cord injury

PubMed Central

Zhang, Peixun; Zhang, Luping; Zhu, Lei; Chen, Fangmin; Zhou, Shuai; Tian, Ting; Zhang, Yuqiang; Jiang, Xiaorui; Li, Xuekun; Zhang, Chuansen; Xu, Lin; Huang, Fei

2015-01-01

Spinal cord injury (SCI) refers to the damage of spinal cord’s structure and function due to a variety of causes. At present, many scholars have confirmed that apoptosis is the main method of secondary injury in spinal cord injury. In view of understanding the function of PI3K/Akt pathway on spinal cord injury, this study observed the temporal variation of key molecules (PI3K, Akt, p-Akt) in the PI3K/Akt pathway after spinal cord injury by immunohistochemistry and Western-blot. The results showed that the expression of PI3K, Akt and p-Akt display a sharp increase one day after the spinal cord injury, and then it decreased gradually with the time passing by, but the absolute expression was certainly higher than the normal group. These results indicate that the PI3K/Akt signaling pathway is involved in the spinal cord injury and the mechanism may be related to apoptosis. PMID:26807170

Adenosine A1-Dopamine D1 Receptor Heteromers Control the Excitability of the Spinal Motoneuron.

PubMed

Rivera-Oliver, Marla; Moreno, Estefanía; Álvarez-Bagnarol, Yocasta; Ayala-Santiago, Christian; Cruz-Reyes, Nicole; Molina-Castro, Gian Carlo; Clemens, Stefan; Canela, Enric I; Ferré, Sergi; Casadó, Vicent; Díaz-Ríos, Manuel

2018-05-24

While the role of the ascending dopaminergic system in brain function and dysfunction has been a subject of extensive research, the role of the descending dopaminergic system in spinal cord function and dysfunction is just beginning to be understood. Adenosine plays a key role in the inhibitory control of the ascending dopaminergic system, largely dependent on functional complexes of specific subtypes of adenosine and dopamine receptors. Combining a selective destabilizing peptide strategy with a proximity ligation assay and patch-clamp electrophysiology in slices from male mouse lumbar spinal cord, the present study demonstrates the existence of adenosine A 1 -dopamine D 1 receptor heteromers in the spinal motoneuron by which adenosine tonically inhibits D 1 receptor-mediated signaling. A 1 -D 1 receptor heteromers play a significant control of the motoneuron excitability, represent main targets for the excitatory effects of caffeine in the spinal cord and can constitute new targets for the pharmacological therapy after spinal cord injury, motor aging-associated disorders and restless legs syndrome.

[RECONSTRUCTION OF LOWER EXTREMITY FUNCTION OF COMPLETE SPINAL CORD INJURY RATS BY FIRST NEURON CONNECTION].

PubMed

Wang, Fangyong; Yuan, Yuan; Li, Jianjun

2015-12-01

To investigate the effects of the first neuron connection for the reconstruction of lower extremity function of complete spinal cord injury rats. Forty adult female Sprague Dawley rats of 300-350 g in weight were selected to prepare the models of L₁ transverse spinal cord injury. After 2 weeks of establishing model, the rats were randomly divided into control group (n = 20) and experimental group (n = 20). In the experimental group, the right hind limb function was reconstructed directly by the first neuron; in the control group, the other treatments were the same to the experimental group except that the distal tibial nerve and the proximal femoral nerve were not sutured. The recovery of motor function of lower extremity was observed by the Basso-Beattie-Bresnahan (BBB) scoring system on bilateral hind limbs at 7, 30, 50, and 70 days after operation. The changes of the spinal cord were observed by HE staining, neurofilament 200 immunohistochemistry staining, and the technique of horseradish peroxidase (HRP) tracing. After establishing models, 6 rats died. The right hind limb had no obvious recovery of the motor function, with the BBB score of 0 in 2 groups; the left hind limb motor function was recovered in different degrees, and there was no significant difference in BBB score between 2 groups (P > 0.05). In the experimental group, HE staining showed that the spinal cord was reconstructed with the sciatic nerve, which was embedded in the spinal cord, and the sciatic nerve membrane was clearly identified, and there was no obvious atrophy in the connecting part of the spinal cord. In the experimental group, the expression of nerve fiber was stained with immunohistochemistry, and the axons of the spinal cord were positively by stained and the peripheral nerve was connected with the spinal cord. HRP labelled synapses were detected by HRP retrograde tracing in the experimental group, while there was no HRP labelled synapse in the control group. Direct reconstruction of the first neurons is sufficient in the regeneration of corresponding neural circuit by the growth of residual axon; but the motor function recovery of the target muscles innervated by peripheral nerve is not observed.

Sexuality and sexual dysfunction in spinal cord-injured men in Turkey.

PubMed

Akman, Ramazan Yavuz; Coşkun Çelik, Evrim; Karataş, Metin

2015-01-01

To provide a comprehensive evaluation of sexual function and dysfunction in spinal cord-injured men based on self-reports of patients. Forty-seven spinal cord-injured men who completed the spinal shock and rehabilitation period were included. Patients were asked to complete a questionnaire developed to assess social status, sexual activities, abilities, and sexuality education after injury. Neurologic levels of patients were classified according to American Spinal Cord Injury Association protocol. Erectile function was evaluated by International Index of Erectile Function-5 (IIEF-5) questionnaire. Patients were aged between 20 and 62 years (mean: 35.2). Twenty-eight patients had T10 and above, 15 between T11 and L2, and 4 cauda conus injury. While 61.7% of the patients declared sexual activity, 93.6% declared some degree of erection. Mean IIEF-5 score was 5.3 and 87.3% of the patients had moderate to severe erectile dysfunction. Continuation of sexual activity after injury is very important and has a great impact on quality of life and interpersonal relationships for spinal cord-injured men. More attention must be given to sexuality after spinal cord injury. A very high rate of sexual dysfunction in spinal cord-injured patients was found and the importance of sexual education was emphasized in this study.

Spinal Interneurons and Forelimb Plasticity after Incomplete Cervical Spinal Cord Injury in Adult Rats

PubMed Central

Rombola, Angela M.; Rousseau, Celeste A.; Mercier, Lynne M.; Fitzpatrick, Garrett M.; Reier, Paul J.; Fuller, David D.; Lane, Michael A.

2015-01-01

Abstract Cervical spinal cord injury (cSCI) disrupts bulbospinal projections to motoneurons controlling the upper limbs, resulting in significant functional impairments. Ongoing clinical and experimental research has revealed several lines of evidence for functional neuroplasticity and recovery of upper extremity function after SCI. The underlying neural substrates, however, have not been thoroughly characterized. The goals of the present study were to map the intraspinal motor circuitry associated with a defined upper extremity muscle, and evaluate chronic changes in the distribution of this circuit following incomplete cSCI. Injured animals received a high cervical (C2) lateral hemisection (Hx), which compromises supraspinal input to ipsilateral spinal motoneurons controlling the upper extremities (forelimb) in the adult rat. A battery of behavioral tests was used to characterize the time course and extent of forelimb motor recovery over a 16 week period post-injury. A retrograde transneuronal tracer – pseudorabies virus – was used to define the motor and pre-motor circuitry controlling the extensor carpi radialis longus (ECRL) muscle in spinal intact and injured animals. In the spinal intact rat, labeling was observed unilaterally within the ECRL motoneuron pool and within spinal interneurons bilaterally distributed within the dorsal horn and intermediate gray matter. No changes in labeling were observed 16 weeks post-injury, despite a moderate degree of recovery of forelimb motor function. These results suggest that recovery of the forelimb function assessed following C2Hx injury does not involve recruitment of new interneurons into the ipsilateral ECRL motor pathway. However, the functional significance of these existing interneurons to motor recovery requires further exploration. PMID:25625912

Anatomy of the Spinal Meninges.

PubMed

Sakka, Laurent; Gabrillargues, Jean; Coll, Guillaume

2016-06-01

The spinal meninges have received less attention than the cranial meninges in the literature, although several points remain debatable and poorly understood, like their phylogenesis, their development, and their interactions with the spinal cord. Their constancy among the chordates shows their crucial importance in central nervous system homeostasis and suggests a role far beyond mechanical protection of the neuraxis. This work provides an extensive study of the spinal meninges, from an overview of their phylogenesis and embryology to a descriptive and topographic anatomy with clinical implications. It examines their involvement in spinal cord development, functioning, and repair. This work is a review of the literature using PubMed as a search engine on Medline. The stages followed by the meninges along the phylogenesis could not be easily compared with their development in vertebrates for methodological aspects and convergence processes throughout evolution. The distinction between arachnoid and pia mater appeared controversial. Several points of descriptive anatomy remain debatable: the functional organization of the arterial network, and the venous and lymphatic drainages, considered differently by classical anatomic and neuroradiological approaches. Spinal meninges are involved in neurodevelopment and neurorepair producing neural stem cells and morphogens, in cerebrospinal fluid dynamics and neuraxis functioning by the synthesis of active molecules, and the elimination of waste products of central nervous system metabolism. The spinal meninges should be considered as dynamic functional formations evolving over a lifetime, with ultrastructural features and functional interactions with the neuraxis remaining not fully understood.

Improving outcome of sensorimotor functions after traumatic spinal cord injury.

PubMed

Dietz, Volker

2016-01-01

In the rehabilitation of a patient suffering a spinal cord injury (SCI), the exploitation of neuroplasticity is well established. It can be facilitated through the training of functional movements with technical assistance as needed and can improve outcome after an SCI. The success of such training in individuals with incomplete SCI critically depends on the presence of physiological proprioceptive input to the spinal cord leading to meaningful muscle activations during movement performances. Some actual preclinical approaches to restore function by compensating for the loss of descending input to spinal networks following complete/incomplete SCI are critically discussed in this report. Electrical and pharmacological stimulation of spinal neural networks is still in the experimental stage, and despite promising repair studies in animal models, translations to humans up to now have not been convincing. It is possible that a combination of techniques targeting the promotion of axonal regeneration is necessary to advance the restoration of function. In the future, refinement of animal models according to clinical conditions and requirements may contribute to greater translational success.

Trends in the surgical treatment for spinal metastasis and the in-hospital patient outcomes in the United States from 2000 to 2009.

PubMed

Yoshihara, Hiroyuki; Yoneoka, Daisuke

2014-09-01

Surgical treatment for spinal metastasis is still controversial. However, with the improvements in treatment for primary tumors, the survival rate of patients with spinal metastasis is enhanced. At the same time, surgical technique for spinal metastasis has also improved. The purpose of this study was to examine trends in the surgical treatment for spinal metastasis and in-hospital patient outcomes on a national level. This was an epidemiologic study using national administrative data from the Nationwide Inpatient Sample (NIS) database. All discharges in the NIS with a diagnosis code of secondary malignant neoplasm of the spinal cord/brain, meninges, or bone who also underwent spinal surgery from 2000 to 2009 were included. Trends in the surgical treatment for spinal metastasis, in-hospital complications and mortality, and resource use were analyzed. The NIS was used to identify patients who underwent surgical treatment for spinal metastasis from 2000 to 2009, using the International Classification of Diseases, Ninth revision, Clinical Modification codes. Trends in the surgical treatment for spinal metastasis and in-hospital patient outcomes were analyzed. From 2000 to 2009, there was an increasing trend in the population growth-adjusted rate of surgical treatment for spinal metastasis (1.15-1.77 per 100,000; p<.001). Average Elixhauser comorbidity score increased over time (2.6-3.8; p<.001), and the overall in-hospital complication rate increased over time (14.8%-27.7%; p<.001), whereas in-hospital mortality rate and length of hospital stay remained stable over time (5.2%-4.6%, p=.413; 10.6-10.8 days, p=.626). Inflation-adjusted mean hospital charges increased more than two-fold over time ($50,390-$110,173; p<.001). During the last decade, surgical treatment for spinal metastasis has increased in the United States. The overall in-hospital complication rate and hospital charges increased, whereas the in-hospital mortality rate and length of hospital stay remained stable. Copyright © 2014 Elsevier Inc. All rights reserved.

Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level

PubMed Central

Brommer, Benedikt; Engel, Odilo; Kopp, Marcel A.; Watzlawick, Ralf; Müller, Susanne; Prüss, Harald; Chen, Yuying; DeVivo, Michael J.; Finkenstaedt, Felix W.; Dirnagl, Ulrich; Liebscher, Thomas; Meisel, Andreas

2016-01-01

Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient’s environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P < 0.001) independently from mechanical ventilation and preserved sensory function by multiple regression analysis. We present evidence that spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS (‘immune paralysis’), sufficient to propagate clinically relevant infection in an injury level dependent manner. PMID:26754788

Tissue-Engineered Regeneration of Hemisected Spinal Cord Using Human Endometrial Stem Cells, Poly ε-Caprolactone Scaffolds, and Crocin as a Neuroprotective Agent.

PubMed

Terraf, Panieh; Kouhsari, Shideh Montasser; Ai, Jafar; Babaloo, Hamideh

2017-09-01

Loss of motor and sensory function as a result of neuronal cell death and axonal degeneration are the hallmarks of spinal cord injury. To overcome the hurdles and achieve improved functional recovery multiple aspects, it must be taken into account. Tissue engineering approaches by coalescing biomaterials and stem cells offer a promising future for treating spinal cord injury. Here we investigated human endometrial stem cells (hEnSCs) as our cell source. Electrospun poly ε-caprolactone (PCL) scaffolds were used for hEnSC adhesion and growth. Scanning electron microscopy (SEM) confirmed the attachment and survival of stem cells on the PCL scaffolds. The scaffold-stem cell construct was transplanted into the hemisected spinal cords of adult male rats. Crocin, an ethanol-extractable component of Crocus sativus L., was administered to rats for 15 consecutive days post injury. Neurite outgrowth and axonal regeneration were investigated using immunohistochemical staining for neurofilament marker NF-H and luxol-fast blue (LFB) staining, respectively. TNF-α staining was performed to determine the inflammatory response in each group. Functional recovery was assessed via the Basso-Beattie-Bresnahan (BBB) scale. Results showed that PCL scaffolds seeded with hEnSCs restored the continuity of the damaged spinal cord and decreased cavity formation. Additionally, hEnSC-seeded scaffolds contributed to the functional recovery of the spinal cord. Hence, hEnSC-seeded PCL scaffolds may serve as promising transplants for spinal cord tissue engineering purposes. Furthermore, crocin had an augmenting effect on spinal cord regeneration and proved to exert neuroprotective effects on damaged neurons and may be further studied as a promising drug for spinal cord injury.

Conditionally immortalized stem cell lines from human spinal cord retain regional identity and generate functional V2a interneurons and motorneurons.

PubMed

Cocks, Graham; Romanyuk, Nataliya; Amemori, Takashi; Jendelova, Pavla; Forostyak, Oksana; Jeffries, Aaron R; Perfect, Leo; Thuret, Sandrine; Dayanithi, Govindan; Sykova, Eva; Price, Jack

2013-06-07

The use of immortalized neural stem cells either as models of neural development in vitro or as cellular therapies in central nervous system (CNS) disorders has been controversial. This controversy has centered on the capacity of immortalized cells to retain characteristic features of the progenitor cells resident in the tissue of origin from which they were derived, and the potential for tumorogenicity as a result of immortalization. Here, we report the generation of conditionally immortalized neural stem cell lines from human fetal spinal cord tissue, which addresses these issues. Clonal neural stem cell lines were derived from 10-week-old human fetal spinal cord and conditionally immortalized with an inducible form of cMyc. The derived lines were karyotyped, transcriptionally profiled by microarray, and assessed against a panel of spinal cord progenitor markers with immunocytochemistry. In addition, the lines were differentiated and assessed for the presence of neuronal fate markers and functional calcium channels. Finally, a clonal line expressing eGFP was grafted into lesioned rat spinal cord and assessed for survival, differentiation characteristics, and tumorogenicity. We demonstrate that these clonal lines (a) retain a clear transcriptional signature of ventral spinal cord progenitors and a normal karyotype after extensive propagation in vitro, (b) differentiate into relevant ventral neuronal subtypes with functional T-, L-, N-, and P/Q-type Ca(2+) channels and spontaneous calcium oscillations, and (c) stably engraft into lesioned rat spinal cord without tumorogenicity. We propose that these cells represent a useful tool both for the in vitro study of differentiation into ventral spinal cord neuronal subtypes, and for examining the potential of conditionally immortalized neural stem cells to facilitate functional recovery after spinal cord injury or disease.

Quality of motion considerations in numerical analysis of motion restoring implants of the spine.

PubMed

Bowden, Anton E; Guerin, Heather L; Villarraga, Marta L; Patwardhan, Avinash G; Ochoa, Jorge A

2008-06-01

Motion restoring implants function in a dynamic environment that encompasses the full range of spinal kinematics. Accurate assessment of the in situ performance of these devices using numerical techniques requires model verification and validation against the well-established nonlinear quality of motion of the spine, as opposed to the previous norm of matching kinematic endpoint metrics such as range of motion and intervertebral disc pressure measurements at a single kinematic reference point. Experimental data was obtained during cadaveric testing of nine three-functional spinal unit (L3-S1) lumbar spine segments. Each specimen was tested from 8 Nm of applied flexion moment to 6 Nm of applied extension moment with an applied 400 N compressive follower preload. A nonlinear kinematic curve representing the spinal quality of motion (applied moment versus angular rotation) for the index finite element model was constructed and compared to the kinematic responses of the experimental specimens. The effect of spinal soft tissue structure mechanical behaviors on the fidelity of the model's quality of motion to experimental data was assessed by iteratively modifying the material representations of annulus fibrosus, nucleus pulposus, and ligaments. The present work demonstrated that for this model, the annulus fibrosus played a small role in the nonlinear quality of motion of the model, whereas changes in ligament representations had a large effect, as validated against the full kinematic range of motion. An anisotropic continuum representation of the annulus fibrosus was used, along with nonlinear fabric representations of the ligaments and a hyperelastic representation of the nucleus pulposus. Our results suggest that improvements in current methodologies broadly used in numerical simulations of the lumbar spine are needed to fully describe the highly nonlinear motion of the spine.

Spinal-Exercise Prescription in Sport: Classifying Physical Training and Rehabilitation by Intention and Outcome

PubMed Central

Spencer, Simon; Wolf, Alex; Rushton, Alison

2016-01-01

Context: Identification of strategies to prevent spinal injury, optimize rehabilitation, and enhance performance is a priority for practitioners. Different exercises produce different effects on neuromuscular performance. Clarity of the purpose of a prescribed exercise is central to a successful outcome. Spinal exercises need to be classified according to the objective of the exercise and planned physical outcome. Objective: To define the modifiable spinal abilities that underpin optimal function during skilled athletic performance, clarify the effect of spinal pain and pathologic conditions, and classify spinal exercises according to the objective of the exercise and intended physical outcomes to inform training and rehabilitation. Design: Qualitative study. Data Collection and Analysis: We conducted a qualitative consensus method of 4 iterative phases. An exploratory panel carried out an extended review of the English-language literature using CINAHL, EMBASE, MEDLINE, and PubMed to identify key themes and subthemes to inform the definitions of exercise categories, physical abilities, and physical outcomes. An expert project group reviewed panel findings. A draft classification was discussed with physiotherapists (n = 49) and international experts. Lead physiotherapy and strength and conditioning teams (n = 17) reviewed a revised classification. Consensus was defined as unanimous agreement. Results: After the literature review and subsequent analysis, we defined spinal abilities in 4 categories: mobility, motor control, work capacity, and strength. Exercises were subclassified by functionality as nonfunctional or functional and by spinal displacement as either static (neutral spinal posture with no segmental displacement) or dynamic (dynamic segmental movement). The proposed terminology and classification support commonality of language for practitioners. Conclusions: The spinal-exercise classification will support clinical reasoning through a framework of spinal-exercise objectives that clearly define the nature of the exercise prescription required to deliver intended physical outcomes. PMID:27661792

Paralysis recovery in humans and model systems

NASA Technical Reports Server (NTRS)

Edgerton, V. Reggie; Roy, Roland R.

2002-01-01

Considerable evidence now demonstrates that extensive functional and anatomical reorganization following spinal cord injury occurs in centers of the brain that have some input into spinal motor pools. This is very encouraging, given the accumulating evidence that new connections formed across spinal lesions may not be initially functionally useful. The second area of advancement in the field of paralysis recovery is in the development of effective interventions to counter axonal growth inhibition. A third area of significant progress is the development of robotic devices to quantify the performance level of motor tasks following spinal cord injury and to 'teach' the spinal cord to step and stand. Advances are being made with robotic devices for mice, rats and humans.

Functional MR imaging of the cervical spinal cord by use of electrical stimulation at LI4 (Hegu).

PubMed

Wang, W D; Kong, K M; Xiao, Y Y; Wang, X J; Liang, B; Qi, W L; Wu, R H

2006-01-01

The purpose is to investigate the cervical spinal cord mapping on electrical stimulation at LI4 (Hegu) by using 'signal enhancement by extravascular water protons' (SEEP)-fMRI, and to establish the response of acupoint-stimulation in spinal cord. Three healthy volunteers were underwent low-frequency electrical stimulation at LI4. Meanwhile, a single-shot fast spin-echo (SSFSE) sequence was used to perform functional MR imaging on a 1.5 T GE Signa MR system. Cord activation was measured both in the sagittal and transverse imaging planes and then analyzed by AFNI (analysis of functional neuroimages) system. In the sagittal view, two subjects had an fMRI response in the cervical spinal cord upon electrical stimulation at LI4. The localizations of the segmental fMRI activation are both at C6 through T1 and C2/3 cervical spinal cord level. In the transverse imaging plane, significant fMRI responses could be measured in the last subjects locating at C6/7 segment, the cross-sectional localization of the activity measured in the spinal cord was most in terms of the ipsilateral posterior direction. It is concluded that the fMRI technique can be used for detecting with activity in the human cervical spinal cord by a single-shot fast spin-echo sequence on a 1.5 T GE clinical system. Investigating the acupoint-stimulation response in the spinal cord using the spinal fMRI will be helpful for the further discussion on the mechanisms of acupuncture to spinal cord diseases.

Biomechanical testing of a polymer-based biomaterial for the restoration of spinal stability after nucleotomy

PubMed Central

Hegewald, Aldemar A; Knecht, Sven; Baumgartner, Daniel; Gerber, Hans; Endres, Michaela; Kaps, Christian; Stüssi, Edgar; Thomé, Claudius

2009-01-01

Background Surgery for disc herniations can be complicated by two major problems: painful degeneration of the spinal segment and re-herniation. Therefore, we examined an absorbable poly-glycolic acid (PGA) biomaterial, which was lyophilized with hyaluronic acid (HA), for its utility to (a) re-establish spinal stability and to (b) seal annulus fibrosus defects. The biomechanical properties range of motion (ROM), neutral zone (NZ) and a potential annulus sealing capacity were investigated. Methods Seven bovine, lumbar spinal units were tested in vitro for ROM and NZ in three consecutive stages: (a) intact, (b) following nucleotomy and (c) after insertion of a PGA/HA nucleus-implant. For biomechanical testing, spinal units were mounted on a loading-simulator for spines. In three cycles, axial loading was applied in an excentric mode with 0.5 Nm steps until an applied moment of ± 7.5 Nm was achieved in flexion/extension. ROM and NZ were assessed. These tests were performed without and with annulus sealing by sewing a PGA/HA annulus-implant into the annulus defect. Results Spinal stability was significantly impaired after nucleotomy (p < 0.001). Intradiscal implantation of a PGA-HA nucleus-implant, however, restored spinal stability (p < 0.003). There was no statistical difference between the stability provided by the nucleus-implant and the intact stage regarding flexion/extension movements (p = 0.209). During the testing sequences, herniation of biomaterial through the annulus defect into the spinal canal regularly occurred, resulting in compression of neural elements. Sewing a PGA/HA annulus-implant into the annulus defect, however, effectively prevented herniation. Conclusion PGA/HA biomaterial seems to be well suited for cell-free and cell-based regenerative treatment strategies in spinal surgery. Its abilities to restore spinal stability and potentially close annulus defects open up new vistas for regenerative approaches to treat intervertebral disc degeneration and for preventing implant herniation. PMID:19604373

Spinal Motocross Injuries in the United Kingdom

PubMed Central

Singh, Rohit; Bhalla, Amit; Ockendon, Matthew; Hay, Stuart

2018-01-01

Background: Motocross is a form of motorcycle racing held on established off-road circuits and has been a recreational and competitive sport across the world for >100 years. In the United Kingdom alone, motocross has grown into a phenomenally ambitious and popular franchise. There are >200 motocross clubs across the country, permitting >900 events annually. Purpose: To assess the current trend of spine-related motocross injuries over the past 5 years. Study Design: Descriptive epidemiology study. Methods: Data were prospectively collected over 5 years (August 2010–August 2015) at our regional trauma and spine unit, regardless of whether the rider was performing the sport competitively or recreationally. Results: During the study period, spine-related injuries were identified for 174 patients (age range, 6-75 years) who were directly referred to our department following recreational or competitive motocross, with most injuries being sustained within the early spring and summer months, representing the start of the motocross season. A significant number of injuries were in males (n = 203, 94%), with the majority of injuries occurring within the 21- to 30-year-old age group. A total of 116 (54%) injuries required operative treatment. The most common spinal injury was thoracolumbar burst fracture (n = 95), followed by chance fractures (n = 26). Conclusion: This data series emphasizes the prevalence and devastation of motocross-related spinal injuries in the United Kingdom and may serve in administering sanctions and guidelines to governing bodies of motocross. The spinal injuries that occur during motocross have significant capital connotations for regional spinal centers. The recent surge in motocross popularity is correlated with the number of injuries, which have increased over the past 5 years by almost 500%. PMID:29349095

Detecting bladder fullness through the ensemble activity patterns of the spinal cord unit population in a somatovisceral convergence environment.

PubMed

Park, Jae Hong; Kim, Chang-Eop; Shin, Jaewoo; Im, Changkyun; Koh, Chin Su; Seo, In Seok; Kim, Sang Jeong; Shin, Hyung-Cheul

2013-10-01

Chronic monitoring of the state of the bladder can be used to notify patients with urinary dysfunction when the bladder should be voided. Given that many spinal neurons respond both to somatic and visceral inputs, it is necessary to extract bladder information selectively from the spinal cord. Here, we hypothesize that sensory information with distinct modalities should be represented by the distinct ensemble activity patterns within the neuronal population and, therefore, analyzing the activity patterns of the neuronal population could distinguish bladder fullness from somatic stimuli. We simultaneously recorded 26-27 single unit activities in response to bladder distension or tactile stimuli in the dorsal spinal cord of each Sprague-Dawley rat. In order to discriminate between bladder fullness and tactile stimulus inputs, we analyzed the ensemble activity patterns of the entire neuronal population. A support vector machine (SVM) was employed as a classifier, and discrimination performance was measured by k-fold cross-validation tests. Most of the units responding to bladder fullness also responded to the tactile stimuli (88.9-100%). The SVM classifier precisely distinguished the bladder fullness from the somatic input (100%), indicating that the ensemble activity patterns of the unit population in the spinal cord are distinct enough to identify the current input modality. Moreover, our ensemble activity pattern-based classifier showed high robustness against random losses of signals. This study is the first to demonstrate that the two main issues of electroneurographic monitoring of bladder fullness, low signals and selectiveness, can be solved by an ensemble activity pattern-based approach, improving the feasibility of chronic monitoring of bladder fullness by neural recording.

Intradermal endothelin-1 excites bombesin-responsive superficial dorsal horn neurons in the mouse

PubMed Central

Akiyama, T.; Nagamine, M.; Davoodi, A.; Iodi Carstens, M.; Cevikbas, F.; Steinhoff, M.

2015-01-01

Endothelin-1 (ET-1) has been implicated in nonhistaminergic itch. Here we used electrophysiological methods to investigate whether mouse superficial dorsal horn neurons respond to intradermal (id) injection of ET-1 and whether ET-1-sensitive neurons additionally respond to other pruritic and algesic stimuli or spinal superfusion of bombesin, a homolog of gastrin-releasing peptide (GRP) that excites spinal itch-signaling neurons. Single-unit recordings were made from lumbar dorsal horn neurons in pentobarbital-anesthetized C57BL/6 mice. We searched for units that exhibited elevated firing after id injection of ET-1 (1 μg/μl). Responsive units were further tested with mechanical stimuli, bombesin (spinal superfusion, 200 μg·ml−1·min−1), heating, cooling, and additional chemicals [histamine, chloroquine, allyl isothiocyanate (AITC), capsaicin]. Of 40 ET-1-responsive units, 48% responded to brush and pinch [wide dynamic range (WDR)] and 52% to pinch only [high threshold (HT)]. Ninety-three percent responded to noxious heat, 50% to cooling, and >70% to histamine, chloroquine, AITC, and capsaicin. Fifty-seven percent responded to bombesin, suggesting that they participate in spinal itch transmission. That most ET-1-sensitive spinal neurons also responded to pruritic and algesic stimuli is consistent with previous studies of pruritogen-responsive dorsal horn neurons. We previously hypothesized that pruritogen-sensitive neurons signal itch. The observation that ET-1 activates nociceptive neurons suggests that both itch and pain signals may be generated by ET-1 to result in simultaneous sensations of itch and pain, consistent with observations that ET-1 elicits both itch- and pain-related behaviors in animals and burning itch sensations in humans. PMID:26311187

An animal model of functional electrical stimulation: evidence that the central nervous system modulates the consequences of training

PubMed Central

Hook, MA; Grau, JW

2011-01-01

Study Design Review of how spinal neurons can modulate the consequences of functional electrical stimulation (FES) in an animal model. Methods Spinal effects of FES are examined in male Sprague–Dawley rats transected at the second thoracic vertebra. The rats are exposed to FES training 24–48 h after surgery. Experimental manipulations of stimulation parameters, combined with physiological and pharmacological procedures, are used to examine the potential role of spinal neurons. Results The isolated spinal cord is inherently capable of learning the response–outcome relations imposed in FES training contingencies. Adaptive behavioral modifications are observed when an outcome (electrical stimulation) is contingent on a behavioral response. In contrast, a lack of correlation between the response and outcome in training produces a learning deficit in the spinal cord, rendering it incapable of adaptive learning for up to 48 h. The N-methyl-D-aspartic acid receptor appears to mediate both the adaptive plasticity and loss of plasticity, seen in this spinal model. Conclusion The behavioral effects observed with FES therapies are not simply due to the direct (motor) consequences of stimulation elicited by the activation of efferent motor neurons and/or selected muscles. FES training has the capacity to shape inherent spinal circuits and to produce a long-lasting behavioral modification. Further understanding of the spinal mechanisms underlying adaptive behavioral modification will be integral for establishing functional neural connections in a regenerating spinal system. PMID:17700514

ASTM F1717 standard for the preclinical evaluation of posterior spinal fixators: can we improve it?

PubMed

La Barbera, Luigi; Galbusera, Fabio; Villa, Tomaso; Costa, Francesco; Wilke, Hans-Joachim

2014-10-01

Preclinical evaluation of spinal implants is a necessary step to ensure their reliability and safety before implantation. The American Society for Testing and Materials reapproved F1717 standard for the assessment of mechanical properties of posterior spinal fixators, which simulates a vertebrectomy model and recommends mimicking vertebral bodies using polyethylene blocks. This set-up should represent the clinical use, but available data in the literature are few. Anatomical parameters depending on the spinal level were compared to published data or measurements on biplanar stereoradiography on 13 patients. Other mechanical variables, describing implant design were considered, and all parameters were investigated using a numerical parametric finite element model. Stress values were calculated by considering either the combination of the average values for each parameter or their worst-case combination depending on the spinal level. The standard set-up represents quite well the anatomy of an instrumented average thoracolumbar segment. The stress on the pedicular screw is significantly influenced by the lever arm of the applied load, the unsupported screw length, the position of the centre of rotation of the functional spine unit and the pedicular inclination with respect to the sagittal plane. The worst-case combination of parameters demonstrates that devices implanted below T5 could potentially undergo higher stresses than those described in the standard suggestions (maximum increase of 22.2% at L1). We propose to revise F1717 in order to describe the anatomical worst case condition we found at L1 level: this will guarantee higher safety of the implant for a wider population of patients. © IMechE 2014.

Select spinal lesions reveal multiple ascending pathways in the rat conveying input from the male genitalia

PubMed Central

Hubscher, C H; Reed, W R; Kaddumi, E G; Armstrong, J E; Johnson, R D

2010-01-01

The specific white matter location of all the spinal pathways conveying penile input to the rostral medulla is not known. Our previous studies using rats demonstrated the loss of low but not high threshold penile inputs to medullary reticular formation (MRF) neurons after acute and chronic dorsal column (DC) lesions of the T8 spinal cord and loss of all penile inputs after lesioning the dorsal three-fifths of the cord. In the present study, select T8 lesions were made and terminal electrophysiological recordings were performed 45–60 days later in a limited portion of the nucleus reticularis gigantocellularis (Gi) and Gi pars alpha. Lesions included subtotal dorsal hemisections that spared only the lateral half of the dorsal portion of the lateral funiculus on one side, dorsal and over-dorsal hemisections, and subtotal transections that spared predominantly just the ventromedial white matter. Electrophysiological data for 448 single unit recordings obtained from 32 urethane-anaesthetized rats, when analysed in groups based upon histological lesion reconstructions, revealed (1) ascending bilateral projections in the dorsal, dorsolateral and ventrolateral white matter of the spinal cord conveying information from the male external genitalia to MRF, and (2) ascending bilateral projections in the ventrolateral white matter conveying information from the pelvic visceral organs (bladder, descending colon, urethra) to MRF. Multiple spinal pathways from the penis to the MRF may correspond to different functions, including those processing affective/pleasure/motivational, nociception, and mating-specific (such as for erection and ejaculation) inputs. PMID:20142271

Congenital Bone Fractures in Spinal Muscular Atrophy: Functional Role for SMN Protein in Bone Remodeling

PubMed Central

Shanmugarajan, Srinivasan; Swoboda, Kathryn J.; Iannaccone, Susan T.; Ries, William L.; Maria, Bernard L.; Reddy, Sakamuri V.

2009-01-01

Spinal muscular atrophy is the second most common fatal childhood disorder. Core clinical features include muscle weakness caused by degenerating lower motor neurons and a high incidence of bone fractures and hypercalcemia. Fractures further compromise quality of life by progression of joint contractures or additional loss of motor function. Recent observations suggest that bone disease in spinal muscular atrophy may not be attributed entirely to lower motor neuron degeneration. The presence of the spinal muscular atrophy disease-determining survival motor neuron gene (SMN), SMN expression, and differential splicing in bone-resorbing osteoclasts was recently discovered. Its ubiquitous expression and the differential expression of splice variants suggest that SMN has specific roles in bone cell function. SMN protein also interacts with osteoclast stimulatory factor. Mouse models of human spinal muscular atrophy disease suggest a potential role of SMN protein in skeletal development. Dual energy x-ray absorptiometry analysis demonstrated a substantial decrease in total bone area and poorly developed caudal vertebra in the mouse model. These mice also had pelvic bone fractures. Studies delineating SMN signaling mechanisms and gene transcription in a cell-specific manner will provide important molecular insights into the pathogenesis of bone disease in children with spinal muscular atrophy. Moreover, understanding bone remodeling in spinal muscular atrophy may lead to novel therapeutic approaches to enhance skeletal health and quality of life. This article reviews the skeletal complications associated with spinal muscular atrophy and describes a functional role for SMN protein in osteoclast development and bone resorption activity. PMID:17761651

[Evaluation of the role of combined TES-MEP and CSEP monitoring during the spinal surgery].

PubMed

Chen, Yu-guang; Peng, Xin-sheng; Wan, Yong; Yang, Jun-lin; Zheng, Zhao-min; Zou, Xue-nong; Li, Fo-bao; Shu, Hai-hua; Xia, Jie-hua; Dou, Yun-ling

2010-02-01

To evaluate of the role of transcranial electrical stimulation motor evoked potential (TES-MEP) in combination with cortical somatosensory evoked potential (CSEP) monitoring during the spinal surgery. TES-MEP on bilateral anterior tibial muscle and flexor hallucal brevis and CSEP on bilateral posterior tibial nerve were observed simultaneously on 293 patients during spinal surgery from July 2006 to April 2009. Intravenous anesthesia was employed in all the patients, a part of which were added low dose of sevoflurane or muscle relaxant. The results of TES-MEP, CSEP and combined monitoring were analyzed statistically. Pre-operative and post-operative motor and sensory functions of spinal cord were compared. Success rate of TES-MEP, CSEP and combined monitoring was 90.8%, 96.9% and 100% respectively. For the judgment of motor function of spinal cord, the sensitivity of TES-MEP and CSEP was 100% and 89.3% respectively and the specificity of 98.4% and 96.9%. The Youden index of the two methods was 0.984 and 0.862. For sensory function, the sensitivity of them was 76.7% and 93.3% respectively and the specificity of 98.7% and 98.0%. The Youden index was 0.754 and 0.913. The sensitivity of combined monitoring was 100%, with the specificity of 96.9%. The Youden index was 0.969. The precision of monitoring motor function of spinal cord with TES-MEP is higher than that with CSEP, however, for sensory function, CSEP is more precise. The sensitivity and precision of combined monitoring for spinal cord function were apparently better than that of unitary TES-MEP or CSEP. The combined TES-MEP and CSEP monitoring is a relatively ideal method.

Assessing forelimb function after unilateral cervical spinal cord injury: novel forelimb tasks predict lesion severity and recovery.

PubMed

Khaing, Zin Z; Geissler, Sydney A; Jiang, Shan; Milman, Brian D; Aguilar, Sandra V; Schmidt, Christine E; Schallert, Timothy

2012-02-10

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. Recently there has been increasing interest in cervical spinal cord injury models because the majority of spinal cord injuries are at cervical levels. Here we examined spontaneous functional recovery of adult rats with either laminectomy or lateral hemisection of the cervical spinal cord at C3-C4. Behavioral tests were carried out, including the forelimb locomotor scale (FLS), a postural instability test (PIT), a pasta-handling test that has been used to assess forepaw digit function and latency to eat, forelimb use during vertical-lateral wall exploration in a cylindrical enclosure, and vibrissae-elicited forelimb placing tests. In addition, a forelimb step-alternation test was developed to assess functional recovery at 12 weeks post-injury. All tests detected cSCI-induced deficits relative to laminectomy. Interestingly, the severity of deficits in the forelimb step-alternation test was associated with more extensive spinal damage, greater impairment, and less recovery in the FLS and other tests. For the pasta-handling test we found that rats with a milder cervical injury (alternators) were more likely to use both forepaws together compared to rats with a more severe injury (non-alternators). In addition, using the PIT, we detected enhanced function of the good limb, suggesting that neural plasticity on the unaffected side of the spinal cord may have occurred to compensate for deficits in the impaired forelimb. These outcome measures should be useful for investigating neural events associated with cSCI, and for developing novel treatment strategies.

Standardization of a spinal cord lesion model and neurologic evaluation using mice

PubMed Central

Borges, Paulo Alvim; Cristante, Alexandre Fogaça; de Barros-Filho, Tarcísio Eloy Pessoa; Natalino, Renato Jose Mendonça; dos Santos, Gustavo Bispo; Marcon, Raphael Marcus

2018-01-01

OBJECTIVE: To standardize a spinal cord lesion mouse model. METHODS: Thirty BALB/c mice were divided into five groups: four experimental groups and one control group (sham). The experimental groups were subjected to spinal cord lesion by a weight drop from different heights after laminectomy whereas the sham group only underwent laminectomy. Mice were observed for six weeks, and functional behavior scales were applied. The mice were then euthanized, and histological investigations were performed to confirm and score spinal cord lesion. The findings were evaluated to prove whether the method of administering spinal cord lesion was effective and different among the groups. Additionally, we correlated the results of the functional scales with the results from the histology evaluations to identify which scale is more reliable. RESULTS: One mouse presented autophagia, and six mice died during the experiment. Because four of the mice that died were in Group 5, Group 5 was excluded from the study. All the functional scales assessed proved to be significantly different from each other, and mice presented functional evolution during the experiment. Spinal cord lesion was confirmed by histology, and the results showed a high correlation between the Basso, Beattie, Bresnahan Locomotor Rating Scale and the Basso Mouse Scale. The mouse function scale showed a moderate to high correlation with the histological findings, and the horizontal ladder test had a high correlation with neurologic degeneration but no correlation with the other histological parameters evaluated. CONCLUSION: This spinal cord lesion mouse model proved to be effective and reliable with exception of lesions caused by a 10-g drop from 50 mm, which resulted in unacceptable mortality. The Basso, Beattie, Bresnahan Locomotor Rating Scale and Basso Mouse Scale are the most reliable functional assessments, and but the horizontal ladder test is not recommended. PMID:29561931

Assessment of Effectiveness of Percutaneous Adhesiolysis in Managing Chronic Low Back Pain Secondary to Lumbar Central Spinal Canal Stenosis

PubMed Central

Manchikanti, Laxmaiah; Cash, Kimberly A.; McManus, Carla D.; Pampati, Vidyasagar

2013-01-01

Background: Chronic persistent low back and lower extremity pain secondary to central spinal stenosis is common and disabling. Lumbar surgical interventions with decompression or fusion are most commonly performed to manage severe spinal stenosis. However, epidural injections are also frequently performed in managing central spinal stenosis. After failure of epidural steroid injections, the next sequential step is percutaneous adhesiolysis and hypertonic saline neurolysis with a targeted delivery. The literature on the effectiveness of percutaneous adhesiolysis in managing central spinal stenosis after failure of epidural injections has not been widely studied. Study Design: A prospective evaluation. Setting: An interventional pain management practice, a specialty referral center, a private practice setting in the United States. Objective: To evaluate the effectiveness of percutaneous epidural adhesiolysis in patients with chronic low back and lower extremity pain with lumbar central spinal stenosis. Methods: Seventy patients were recruited. The initial phase of the study was randomized, double-blind with a comparison of percutaneous adhesiolysis with caudal epidural injections. The 25 patients from the adhesiolysis group continued with follow-up, along with 45 additional patients, leading to a total of 70 patients. All patients received percutaneous adhesiolysis and appropriate placement of the Racz catheter, followed by an injection of 5 mL of 2% preservative-free lidocaine with subsequent monitoring in the recovery room. In the recovery room, each patient also received 6 mL of 10% hypertonic sodium chloride solution, and 6 mg of non-particulate betamethasone, followed by an injection of 1 mL of sodium chloride solution and removal of the catheter. Outcomes Assessment: Multiple outcome measures were utilized including the Numeric Rating Scale (NRS), the Oswestry Disability Index 2.0 (ODI), employment status, and opioid intake with assessment at 3, 6, and 12, 18 and 24 months post treatment. The primary outcome measure was 50% or more improvement in pain scores and ODI scores. Results: Overall, a primary outcome or significant pain relief and functional status improvement of 50% or more was seen in 71% of patients at the end of 2 years. The overall number of procedures over a period of 2 years were 5.7 ± 2.73. Limitations: The lack of a control group and a prospective design. Conclusions: Significant relief and functional status improvement as seen in 71% of the 70 patients with percutaneous adhesiolysis utilizing local anesthetic steroids and hypertonic sodium chloride solution may be an effective management strategy in patients with chronic function limiting low back and lower extremity pain with central spinal stenosis after failure of conservatie management and fluoroscopically directed epidural injections. PMID:23289005

Spinal Cord Infarction in Clinical Neurology: A Review of Characteristics and Long-Term Prognosis in Comparison to Cerebral Infarction.

PubMed

Romi, Fredrik; Naess, Halvor

2016-01-01

Spinal cord stroke is rare accounting for 0.3-1% of all strokes and is classified into upper (cervical) and lower (thoracolumbar) strokes. Patients present with severe deficits but later often show good functional improvement. On admission, younger age, male gender, hypertension, diabetes mellitus and elevated blood glucose indicate more severe spinal cord strokes. Treatment of these risk factors is essential in the acute phase. Biphasic spinal cord strokes are seen in one-fifth of the patients. These present with acute or transient sensory spinal cord deficits often preceded by radiating pain between the shoulders, and should be considered and treated as imminent spinal cord strokes. Spinal cord infarction patients are younger and more often women compared to cerebral infarction patients. Traditional cerebrovascular risk factors are less relevant in spinal cord infarction. Spinal cord infarction patients are more likely to be discharged home and show better improvement after initial treatment compared to cerebral infarction patients. On long-term follow-up, spinal cord infarction patients have lower mortality and higher emotional well-being scores than cerebral infarction patients. Despite more chronic pain, the frequency of re-employment is higher among spinal cord infarction patients compared to cerebral infarction patients who are more often afflicted with cognitive function deficits. © 2016 S. Karger AG, Basel.

Functional characterization of mouse spinal cord infiltrating CD8+ lymphocytes

PubMed Central

Deb, Chandra; Howe, Charles L

2011-01-01

Understanding the immunopathogenesis of neuroimmunological diseases of the CNS requires a robust method for isolating and characterizing the immune effector cells that infiltrate the spinal cord in animal models. We have developed a simple and rapid isolation method that produces high yields of spinal cord infiltrating leukocytes from a single demyelinated spinal cord and which maintains high surface expression of key immunophenotyping antigens. Using this method and the Theiler’s virus model of chronic demyelination, we report the presence of spinal cord infiltrating acute effector CD8+ lymphocytes that are CD45hiCD44loCD62L− and a population of spinal cord infiltrating target effector memory CD8+ lymphocytes that are CD45hiCD44hiCD62L−. These cells respond robustly to ex vivo stimulation by producing interferon γ but do not exhibit specificity for Theiler’s virus in a cytotoxicity assay. We conclude that target-derived lymphocytes in a mouse model of chronic spinal cord demyelination may have unique functional specificities. PMID:19596449

Trends of spinal tuberculosis research (1994-2015): A bibliometric study.

PubMed

Wang, Yiran; Wang, Qijin; Zhu, Rongbo; Yang, Changwei; Chen, Ziqiang; Bai, Yushu; Li, Ming; Zhai, Xiao

2016-09-01

Spinal tuberculosis is the most common form of skeletal tuberculosis. However, there were limited data to evaluate the trend of spinal tuberculosis research. This study aims to investigate the trend of spinal tuberculosis research and compare the contribution of research from different countries and authors. Spinal tuberculosis-related publications from 1994 to 2015 were retrieved from the Web of Science database. Excel 2013, GraphPad Prism 5, and VOSviewer software were used to analyze the search results for number of publications, cited frequency, H-index, and country contributions. A total of 1558 papers were identified and were cited 16,152 times as of January 25, 2016. The United States accounted for 15.1% of the articles, 22.3% of the citations, and the highest H-index (33). China ranked third in total number of articles, fifth in citation frequency (815), and ranked seventh in H-index (13). The journal Spine (IF 2.297) had the highest number of publications. The author Jain A.K. has published the most papers in this field (20). The article titled "Tuberculosis of the spine: Controversies and a new challenge" was the most popular article and cited a total of 1138 times. The keyword "disease" was mentioned the most for 118 times and the word "bone fusion" was the latest hotspot by 2015. Literature growth in spinal tuberculosis is slowly expanding. Although publications from China are increasing, the quality of the articles still requires improvements. Meanwhile, the United States continues to be the largest contributor in the field of spinal tuberculosis. According to our bibliometric study, bone fusion may be an emerging topic within spinal tuberculosis research and is something that should be closely observed.

TEMPORAL NEUROTRANSMITTER CONDITIONING RESTORES THE FUNCTIONAL ACTIVITY OF ADULT SPINAL-CORD NEURONS IN LONG-TERM CULTURE

PubMed Central

Das, Mainak; Bhargava, Neelima; Bhalkikar, Abhijeet; Kang, Jung Fong; Hickman, James J

2008-01-01

The ability to culture functional adult mammalian spinal-cord neurons represents an important step in the understanding and treatment of a spectrum of neurological disorders including spinal cord injury. Previously, the limited functional recovery of these cells, as characterized by a diminished ability to initiate action potentials and to exhibit repetitive firing patterns, has arisen as a major impediment to their physiological relevance. In this report we demonstrate that single temporal doses of the neurotransmitters serotonin, glutamate (N-acetyl-DL-glutamic acid) and acetylcholine-chloride leads to the full electrophysiological functional recovery of adult mammalian spinal-cord neurons, when they are cultured under defined serum-free conditions. Approximately 60% of the neurons treated regained their electrophysiological signature, often firing single, double and, most importantly, multiple action potentials. PMID:18005959

Neuromodulation of the neural circuits controlling the lower urinary tract

PubMed Central

Gad, Parag N.; Roy, Roland R.; Zhong, Hui; Gerasimenko, Yury P.; Taccola, Giuliano; Edgerton, V. Reggie

2017-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner. PMID:27381425

Genetically identified spinal interneurons integrating tactile afferents for motor control

PubMed Central

Panek, Izabela; Farah, Carl

2015-01-01

Our movements are shaped by our perception of the world as communicated by our senses. Perception of sensory information has been largely attributed to cortical activity. However, a prior level of sensory processing occurs in the spinal cord. Indeed, sensory inputs directly project to many spinal circuits, some of which communicate with motor circuits within the spinal cord. Therefore, the processing of sensory information for the purpose of ensuring proper movements is distributed between spinal and supraspinal circuits. The mechanisms underlying the integration of sensory information for motor control at the level of the spinal cord have yet to be fully described. Recent research has led to the characterization of spinal neuron populations that share common molecular identities. Identification of molecular markers that define specific populations of spinal neurons is a prerequisite to the application of genetic techniques devised to both delineate the function of these spinal neurons and their connectivity. This strategy has been used in the study of spinal neurons that receive tactile inputs from sensory neurons innervating the skin. As a result, the circuits that include these spinal neurons have been revealed to play important roles in specific aspects of motor function. We describe these genetically identified spinal neurons that integrate tactile information and the contribution of these studies to our understanding of how tactile information shapes motor output. Furthermore, we describe future opportunities that these circuits present for shedding light on the neural mechanisms of tactile processing. PMID:26445867

Intelligence and cognitive function in children and adolescents with spinal muscular atrophy.

PubMed

von Gontard, A; Zerres, K; Backes, M; Laufersweiler-Plass, C; Wendland, C; Melchers, P; Lehmkuhl, G; Rudnik-Schöneborn, S

2002-02-01

Spinal muscular atrophy is a chronic disease characterised by loss of motor function. The aim of the study was to analyse cognitive functions in a large group of patients with spinal muscular atrophy. It was hypothesised that their intelligence is comparable to controls, but not above average as previously postulated. Ninety-six children and adolescents with spinal muscular atrophy I-III, aged 6.0-18.11 years, 45 non-affected siblings and 59 healthy, matched controls were examined with one- (CPM/SPM), as well as multi-dimensional intelligence tests (Kaufman-ABC; Wechsler tests). The mean IQ measured with the CPM/SPM tests was 109.6 for the spinal muscular atrophy group, 107.3 for the sibs and 104.1 for the healthy controls (no significant difference). In the older children and adolescents (SPM only) the mean IQ was significantly higher for the spinal muscular atrophy patients (109.6) than for the controls (95.4). The standard score in the 'mental processing composite' scale of the Kaufman-ABC was identical in the spinal muscular atrophy group and controls (103.8). The cognitive profile was relatively homogeneous. However, the older children and adolescents did have a significantly higher verbal IQ (113.8) than controls (104.6) in the Wechsler tests. There were no significant differences in any of the tests among different grades of severity (spinal muscular atrophy types I-III). It can be concluded that children and adolescents with spinal muscular atrophy have a general intelligence in the normal range. By adolescence, environmentally mediated aspects of intelligence are higher in patients with spinal muscular atrophy. It could be speculated that the development of cognitive skills and knowledge is a creative way to compensate the many restrictions due to their physical handicap.

[Effect of local hypothermia on H- and M-responses after spinal cord contusion in dogs].

PubMed

Iafarova, G G; Tumakaev, R F; Khazieva, A R; Baltina, T V

2014-01-01

In this study we investigated a motor-neuronal functional state based on H- and M-responses from m. quadratus plantae in dogs before and after experimental spinal cord contusion with and without following local intraoperative hypothermia. H- and M-responses from m. quadratus plantae were recorded during stimulation of the tibial nerve and results were compared between the groups. Our results demonstrate that local hypothermia applied after spinal cord contusion reduces amplitude of both M- and H-responses and also H(max)/M(max) ratio that may indicate depression of motorneurons excitability. After spinal cord contusion without following hypothermia the excitability of the spinal motorneurons during post-traumatic period, in opposite, was significantly increased. These results support a conclusion that intraoperative hypothermia after spinal cord contusion can delay development of functional excitability of the motoneurons and protect from further changes in H- and M-responses.

Tonic and Rhythmic Spinal Activity Underlying Locomotion.

PubMed

Ivanenko, Yury P; Gurfinkel, Victor S; Selionov, Victor A; Solopova, Irina A; Sylos-Labini, Francesca; Guertin, Pierre A; Lacquaniti, Francesco

2017-05-12

In recent years, many researches put significant efforts into understanding and assessing the functional state of the spinal locomotor circuits in humans. Various techniques have been developed to stimulate the spinal cord circuitries, which may include both diffuse and quite specific tuning effects. Overall, the findings indicate that tonic and rhythmic spinal activity control are not separate phenomena but are closely integrated to properly initiate and sustain stepping. The spinal cord does not simply transmit information to and from the brain. Its physiologic state determines reflex, postural and locomotor control and, therefore, may affect the recovery of the locomotor function in individuals with spinal cord and brain injuries. This review summarizes studies that examine the rhythmogenesis capacity of cervical and lumbosacral neuronal circuitries in humans and its importance in developing central pattern generator-modulating therapies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Clinical and genetic diversity of SMN1-negative proximal spinal muscular atrophies

PubMed Central

Jordanova, Albena

2014-01-01

Hereditary spinal muscular atrophy is a motor neuron disorder characterized by muscle weakness and atrophy due to degeneration of the anterior horn cells of the spinal cord. Initially, the disease was considered purely as an autosomal recessive condition caused by loss-of-function SMN1 mutations on 5q13. Recent developments in next generation sequencing technologies, however, have unveiled a growing number of clinical conditions designated as non-5q forms of spinal muscular atrophy. At present, 16 different genes and one unresolved locus are associated with proximal non-5q forms, having high phenotypic variability and diverse inheritance patterns. This review provides an overview of the current knowledge regarding the phenotypes, causative genes, and disease mechanisms associated with proximal SMN1-negative spinal muscular atrophies. We describe the molecular and cellular functions enriched among causative genes, and discuss the challenges in the post-genomics era of spinal muscular atrophy research. PMID:24970098

A Review on Locomotor Training after Spinal Cord Injury: Reorganization of Spinal Neuronal Circuits and Recovery of Motor Function

PubMed Central

2016-01-01

Locomotor training is a classic rehabilitation approach utilized with the aim of improving sensorimotor function and walking ability in people with spinal cord injury (SCI). Recent studies have provided strong evidence that locomotor training of persons with clinically complete, motor complete, or motor incomplete SCI induces functional reorganization of spinal neuronal networks at multisegmental levels at rest and during assisted stepping. This neuronal reorganization coincides with improvements in motor function and decreased muscle cocontractions. In this review, we will discuss the manner in which spinal neuronal circuits are impaired and the evidence surrounding plasticity of neuronal activity after locomotor training in people with SCI. We conclude that we need to better understand the physiological changes underlying locomotor training, use physiological signals to probe recovery over the course of training, and utilize established and contemporary interventions simultaneously in larger scale research studies. Furthermore, the focus of our research questions needs to change from feasibility and efficacy to the following: what are the physiological mechanisms that make it work and for whom? The aforementioned will enable the scientific and clinical community to develop more effective rehabilitation protocols maximizing sensorimotor function recovery in people with SCI. PMID:27293901

Electrical stimulation of transplanted motoneurons improves motor unit formation

PubMed Central

Liu, Yang; Grumbles, Robert M.

2014-01-01

Motoneurons die following spinal cord trauma and with neurological disease. Intact axons reinnervate nearby muscle fibers to compensate for the death of motoneurons, but when an entire motoneuron pool dies, there is complete denervation. To reduce denervation atrophy, we have reinnervated muscles in Fisher rats from local transplants of embryonic motoneurons in peripheral nerve. Since growth of axons from embryonic neurons is activity dependent, our aim was to test whether brief electrical stimulation of the neurons immediately after transplantation altered motor unit numbers and muscle properties 10 wk later. All surgical procedures and recordings were done in anesthetized animals. The muscle consequences of motoneuron death were mimicked by unilateral sciatic nerve section. One week later, 200,000 embryonic day 14 and 15 ventral spinal cord cells, purified for motoneurons, were injected into the tibial nerve 10–15 mm from the gastrocnemii muscles as the only neuron source for muscle reinnervation. The cells were stimulated immediately after transplantation for up to 1 h using protocols designed to examine differential effects due to pulse number, stimulation frequency, pattern, and duration. Electrical stimulation that included short rests and lasted for 1 h resulted in higher motor unit counts. Muscles with higher motor unit counts had more reinnervated fibers and were stronger. Denervated muscles had to be stimulated directly to evoke contractions. These results show that brief electrical stimulation of embryonic neurons, in vivo, has long-term effects on motor unit formation and muscle force. This muscle reinnervation provides the opportunity to use patterned electrical stimulation to produce functional movements. PMID:24848463

Can the mammalian lumbar spinal cord learn a motor task?

PubMed

Hodgson, J A; Roy, R R; de Leon, R; Dobkin, B; Edgerton, V R

1994-12-01

Progress toward restoring locomotor function in low thoracic spinal transected cats and the application of similar techniques to patients with spinal cord injury is reviewed. Complete spinal cord transection (T12-T13) in adult cats results in an immediate loss of locomotor function in the hindlimbs. Limited locomotor function returns after several months in cats that have not received specific therapies designed to restore hindlimb stepping. Training transected cats to step on a treadmill for 30 min.d-1 and 5 d.wk-1 greatly improves their stepping ability. The most successful outcome was in cats where training began early, i.e., 1 wk after spinal transection. Cats trained to stand instead of stepping had great difficulty using the hindlimbs for locomotion. These effects were reversible over a 20-month period such that cats unable to step as a result of standing training could be trained to step and, conversely, locomotion in stepping-trained cats could be abolished by standing training. These results indicate that the spinal cord is capable of learning specific motor tasks. It has not been possible to elicit locomotion in patients with clinically complete spinal injuries, but appropriately coordinated EMG activity has been demonstrated in musculature of the legs during assisted locomotion on a treadmill.

Search and Neutralize Factors (Cspgs) that Induce Decline in Transmission to Motoneurons from Spared Fibers after Chronic Spinal Cord Injury

DTIC Science & Technology

2014-04-01

conducted experiments using intraspinal injections of AAV10-NG2Ab combined with AAV10 vector expressing neurotrophin 3 (AAV10-NT3-gfp) in adult rat...mediated delivery of NG2-Ab and neurotrophin NT3 expressing units significantly improved locomotor function following SCI. These behavioral improvements...mediated delivery of NG2-Ab combined with neurotrophin NT3 in rats that received either hemisection or contusion SCI. We found that rats that

Angle-ply biomaterial scaffold for annulus fibrosus repair replicates native tissue mechanical properties, restores spinal kinematics, and supports cell viability.

PubMed

Borem, Ryan; Madeline, Allison; Walters, Joshua; Mayo, Henry; Gill, Sanjitpal; Mercuri, Jeremy

2017-08-01

Annulus fibrosus (AF) damage commonly occurs due to intervertebral disc (IVD) degeneration/herniation. The dynamic mechanical role of the AF is essential for proper IVD function and thus it is imperative that biomaterials developed to repair the AF withstand the mechanical rigors of the native tissue. Furthermore, these biomaterials must resist accelerated degradation within the proteolytic environment of degenerate IVDs while supporting integration with host tissue. We have previously reported a novel approach for developing collagen-based, multi-laminate AF repair patches (AFRPs) that mimic the angle-ply architecture and basic tensile properties of the human AF. Herein, we further evaluate AFRPs for their: tensile fatigue and impact burst strength, IVD attachment strength, and contribution to functional spinal unit (FSU) kinematics following IVD repair. Additionally, AFRP resistance to collagenase degradation and cytocompatibility were assessed following chemical crosslinking. In summary, AFRPs demonstrated enhanced durability at high applied stress amplitudes compared to human AF and withstood radially-directed biaxial stresses commonly borne by the native tissue prior to failure/detachment from IVDs. Moreover, FSUs repaired with AFRPs and nucleus pulposus (NP) surrogates had their axial kinematic parameters restored to intact levels. Finally, carbodiimide crosslinked AFRPs resisted accelerated collagenase digestion without detrimentally effecting AFRP tensile properties or cytocompatibility. Taken together, AFRPs demonstrate the mechanical robustness and enzymatic stability required for implantation into the damaged/degenerate IVD while supporting AF cell infiltration and viability. The quality of life for millions of individuals globally is detrimentally impacted by IVD degeneration and herniation. These pathologies often result in the structural demise of IVD tissue, particularly the annulus fibrosus (AF). Biomaterials developed for AF repair have yet to demonstrate the mechanical strength and durability required for utilization in the spine. Herein, we demonstrate the development of an angle-ply AF repair patch (AFRP) that can resist the application of physiologically relevant stresses without failure and which contributes to the restoration of functional spinal unit axial kinematics following repair. Furthermore, we show that this biomaterial can resist accelerated degradation in a simulated degenerate environment and supports AF cell viability. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Traumatic spinal injuries on farms: Patients treated in the national spinal unit of Ireland 2005-2015.

PubMed

Berney, Mark J; Horstmann, Ellen; Cassidy, Noelle

2017-03-01

Farming is a major industry in Ireland, employing 6% of the workforce but accounts for 40% of workplace fatalities (Meredith, 2008). 1 The use of machinery and proximity to large livestock poses significant risk for spinal injuries. This study reviews mechanism of injury, injuries sustained, and the treatment undertaken. Of 31 patients, 26 sustained high-energy injuries with machinery and livestock implicated in the majority of accidents. 77% sustained poly-trauma and 52% had permanent neurological injury. The proximity to heavy machinery and livestock pose significant risk for spinal injuries. This study should encourage increased efforts to improve farm safety.

International comparison of the organisation of rehabilitation services and systems of care for patients with spinal cord injury.

PubMed

New, P W; Townson, A; Scivoletto, G; Post, M W M; Eriks-Hoogland, I; Gupta, A; Smith, E; Reeves, R K; Gill, Z A

2013-01-01

Survey. Describe and compare the organisation and delivery of rehabilitation services and systems of care for patients with spinal cord injury (SCI). International. Nine spinal rehabilitation units that manage traumatic SCI and non-traumatic SCI (NTSCI) patients. Survey based on clinical expertise and literature review. Completed between November 2010 and April 2011. All units reported public/government funding. Additional funding sources included compensation schemes, private insurance and self funding. Six units had formal attachment to an acute SCI unit. Five units (Italy, Ireland, India, Pakistan and Switzerland) provided a national service; two units (the Netherlands and USA) provided regional and two units (Australia and Canada) provided state/provincial services. The median number of SCI rehabilitation beds was 23 (interquartile range=16-30). All units admitted both traumatic SCI and NTSCI patients. The median proportion of patients admitted who had traumatic SCI was 45% (IQR 20-48%) and 40% (IQR 30-42%) had NTSCI. The rehabilitation team in all centres determined patient readiness for discharge. There was great variability between units in the availability of SCI speciality services, ancillary services and staff/patient ratios. There was a wide range of differences in the organisation, systems of care and services available for patients with SCI in rehabilitation units in different countries. Understanding these differences is important when comparing patient outcomes from different settings. A standardised collection of these system variables should be considered as part of future studies and could be included in the ISCoS data set project.

Spinal cord injury: overview of experimental approaches used to restore locomotor activity.

PubMed

Fakhoury, Marc

2015-01-01

Spinal cord injury affects more than 2.5 million people worldwide and can lead to paraplegia and quadriplegia. Anatomical discontinuity in the spinal cord results in disruption of the impulse conduction that causes temporary or permanent changes in the cord's normal functions. Although axonal regeneration is limited, damage to the spinal cord is often accompanied by spontaneous plasticity and axon regeneration that help improve sensory and motor skills. The recovery process depends mainly on synaptic plasticity in the preexisting circuits and on the formation of new pathways through collateral sprouting into neighboring denervated territories. However, spontaneous recovery after spinal cord injury can go on for several years, and the degree of recovery is very limited. Therefore, the development of new approaches that could accelerate the gain of motor function is of high priority to patients with damaged spinal cord. Although there are no fully restorative treatments for spinal injury, various rehabilitative approaches have been tested in animal models and have reached clinical trials. In this paper, a closer look will be given at the potential therapies that could facilitate axonal regeneration and improve locomotor recovery after injury to the spinal cord. This article highlights the application of several interventions including locomotor training, molecular and cellular treatments, and spinal cord stimulation in the field of rehabilitation research. Studies investigating therapeutic approaches in both animal models and individuals with injured spinal cords will be presented.

Targeting L-Selectin to Improve Neurologic and Urologic Function After Spinal Cord Injury

DTIC Science & Technology

2015-10-01

demonstrated locomotor recovery in mice receiving 40mg/kg DFA up to 3 hours following spinal cord injury -We demonstrated improved locomotor recovery...health, as evaluated by body weight -We identified no added locomotor recovery due to multiple, successive doses of DFA. Moreover, additional doses...bladder function Significance: We have identified robust locomotor recovery in both mild and severe spinal cord injured mice that received DFA up

Axon and dendrite geography predict the specificity of synaptic connections in a functioning spinal cord network.

PubMed

Li, Wen-Chang; Cooke, Tom; Sautois, Bart; Soffe, Stephen R; Borisyuk, Roman; Roberts, Alan

2007-09-10

How specific are the synaptic connections formed as neuronal networks develop and can simple rules account for the formation of functioning circuits? These questions are assessed in the spinal circuits controlling swimming in hatchling frog tadpoles. This is possible because detailed information is now available on the identity and synaptic connections of the main types of neuron. The probabilities of synapses between 7 types of identified spinal neuron were measured directly by making electrical recordings from 500 pairs of neurons. For the same neuron types, the dorso-ventral distributions of axons and dendrites were measured and then used to calculate the probabilities that axons would encounter particular dendrites and so potentially form synaptic connections. Surprisingly, synapses were found between all types of neuron but contact probabilities could be predicted simply by the anatomical overlap of their axons and dendrites. These results suggested that synapse formation may not require axons to recognise specific, correct dendrites. To test the plausibility of simpler hypotheses, we first made computational models that were able to generate longitudinal axon growth paths and reproduce the axon distribution patterns and synaptic contact probabilities found in the spinal cord. To test if probabilistic rules could produce functioning spinal networks, we then made realistic computational models of spinal cord neurons, giving them established cell-specific properties and connecting them into networks using the contact probabilities we had determined. A majority of these networks produced robust swimming activity. Simple factors such as morphogen gradients controlling dorso-ventral soma, dendrite and axon positions may sufficiently constrain the synaptic connections made between different types of neuron as the spinal cord first develops and allow functional networks to form. Our analysis implies that detailed cellular recognition between spinal neuron types may not be necessary for the reliable formation of functional networks to generate early behaviour like swimming.

Fractionated radiation facilitates repair and functional motor recovery after spinal cord transection in rat.

PubMed

Kalderon, N; Xu, S; Koutcher, J A; Fuks, Z

2001-06-22

Previous studies suggest that motor recovery does not occur after spinal cord injury because reactive glia abort the natural repair processes. A permanent wound gap is left in the cord and the brain-cord circuitry consequently remains broken. Single-dose x-irradiation destroys reactive glia at the damage site in transected adult rat spinal cord. The wound then heals naturally, and a partially functional brain-cord circuitry is reconstructed. Timing is crucial; cell ablation is beneficial only within the third week after injury. Data presented here point to the possibility of translating these observations into a clinical therapy for preventing the paralysis following spinal cord injury in the human. The lesion site (at low thoracic level) in severed adult rat spinal cord was treated daily, over the third week postinjury, with protocols of fractionated radiation similar to those for treating human spinal cord tumors. This resulted, as with the single-dose protocol, in wound healing and restoration of some hindquarter motor function; in addition, the beneficial outcome was augmented. Of the restored hindlimb motor functions, weight-support and posture in stance was the only obvious one. Recovery of this motor function was partial to substantial and its incidence was 100% instead of about 50% obtained with the single-dose treatment. None of the hindlimbs, however, regained frequent stepping or any weight-bearing locomotion. These data indicate that the therapeutic outcome may be further augmented by tuning the radiation parameters within the critical time-window after injury. These data also indicate that dose-fractionation is an effective strategy and better than the single-dose treatment for targeting of reactive cells that abort the natural repair, suggesting that radiation therapy could be developed into a therapeutic procedure for repairing injured spinal cord.

Transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into rat spinal cord injuries does not cause harm.

PubMed

Cloutier, Frank; Siegenthaler, Monica M; Nistor, Gabriel; Keirstead, Hans S

2006-07-01

Demyelination contributes to loss of function following spinal cord injury. We have shown previously that transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into adult rat 200 kD contusive spinal cord injury sites enhances remyelination and promotes recovery of motor function. Previous studies using oligodendrocyte lineage cells have noted a correlation between the presence of demyelinating pathology and the survival and migration rate of the transplanted cells. The present study compared the survival and migration of human embryonic stem cell-derived oligodendrocyte progenitors injected 7 days after a 200 or 50 kD contusive spinal cord injury, as well as the locomotor outcome of transplantation. Our findings indicate that a 200 kD spinal cord injury induces extensive demyelination, whereas a 50 kD spinal cord injury induces no detectable demyelination. Cells transplanted into the 200 kD injury group survived, migrated, and resulted in robust remyelination, replicating our previous studies. In contrast, cells transplanted into the 50 kD injury group survived, exhibited limited migration, and failed to induce remyelination as demyelination in this injury group was absent. Animals that received a 50 kD injury displayed only a transient decline in locomotor function as a result of the injury. Importantly, human embryonic stem cell-derived oligodendrocyte progenitor transplants into the 50 kD injury group did not cause a further decline in locomotion. Our studies highlight the importance of a demyelinating pathology as a prerequisite for the function of transplanted myelinogenic cells. In addition, our results indicate that transplantation of human embryonic stem cell-derived oligodendrocyte progenitor cells into the injured spinal cord is not associated with a decline in locomotor function.

Muscle spindle feedback directs locomotor recovery and circuit reorganization after spinal cord injury.

PubMed

Takeoka, Aya; Vollenweider, Isabel; Courtine, Grégoire; Arber, Silvia

2014-12-18

Spinal cord injuries alter motor function by disconnecting neural circuits above and below the lesion, rendering sensory inputs a primary source of direct external drive to neuronal networks caudal to the injury. Here, we studied mice lacking functional muscle spindle feedback to determine the role of this sensory channel in gait control and locomotor recovery after spinal cord injury. High-resolution kinematic analysis of intact mutant mice revealed proficient execution in basic locomotor tasks but poor performance in a precision task. After injury, wild-type mice spontaneously recovered basic locomotor function, whereas mice with deficient muscle spindle feedback failed to regain control over the hindlimb on the lesioned side. Virus-mediated tracing demonstrated that mutant mice exhibit defective rearrangements of descending circuits projecting to deprived spinal segments during recovery. Our findings reveal an essential role for muscle spindle feedback in directing basic locomotor recovery and facilitating circuit reorganization after spinal cord injury. Copyright © 2014 Elsevier Inc. All rights reserved.

Ecto-domain phosphorylation promotes functional recovery from spinal cord injury

PubMed Central

Suehiro, Kenji; Nakamura, Yuka; Xu, Shuai; Uda, Youichi; Matsumura, Takafumi; Yamaguchi, Yoshiaki; Okamura, Hitoshi; Yamashita, Toshihide; Takei, Yoshinori

2014-01-01

Inhibition of Nogo-66 receptor (NgR) can promote recovery following spinal cord injury. The ecto-domain of NgR can be phosphorylated by protein kinase A (PKA), which blocks activation of the receptor. Here, we found that infusion of PKA plus ATP into the damaged spinal cord can promote recovery of locomotor function. While significant elongation of cortical-spinal axons was not detectable even in the rats showing enhanced recovery, neuronal precursor cells were observed in the region where PKA plus ATP were directly applied. NgR1 was expressed in neural stem/progenitor cells (NSPs) derived from the adult spinal cord. Both an NgR1 antagonist NEP1-40 and ecto-domain phosphorylation of NgR1 promote neuronal cell production of the NSPs, in vitro. Thus, inhibition of NgR1 in NSPs can promote neuronal cell production, which could contribute to the enhanced recovery of locomotor function following infusion of PKA and ATP. PMID:24826969

A Fully Implantable Stimulator With Wireless Power and Data Transmission for Experimental Investigation of Epidural Spinal Cord Stimulation.

PubMed

Xu, Qi; Hu, Dingyin; Duan, Bingyu; He, Jiping

2015-07-01

Epidural spinal cord stimulation (ESCS) combined with partial weight-bearing therapy (PWBT) has been shown to facilitate recovery of functional walking for individuals after spinal cord injury (SCI). The investigation of neural mechanisms of recovery from SCI under this treatment has been conducted broadly in rodent models, yet a suitable ESCS system is still unavailable. This paper describes a practical, programmable, and fully implantable stimulator for laboratory research on rats to explore fundamental neurophysiological principles for functional recovery after SCI. The ESCS system is composed of a personal digital assistant (PDA), an external controller, an implantable pulse generator (IPG), lead extension, and stimulating electrodes. The stimulation parameters can be programmed and adjusted through a graphical user interface on the PDA. The external controller is placed on the rat back and communicates with the PDA via radio-frequency (RF) telemetry. An RF carrier from the class-E power amplifier in the external controller provides both data and power for the IPG through an inductive link. The IPG is built around a microcontroller unit to generate voltage-regulated pulses delivered to the bipolar electrode for ESCS in rats. The encapsulated IPG measures 22 mm × 23 mm × 7 mm with a mass of  ∼  3.78 g. This fully implantable batteryless stimulator provided a simplified and efficient method to carry out chronic experiments in untethered animals for medical electro-neurological research.

Functional restoration of the paralyzed diaphragm in high cervical quadriplegia via phrenic nerve neurotization utilizing the functional spinal accessory nerve.

PubMed

Yang, Ming-liang; Li, Jian-jun; Zhang, Shao-cheng; Du, Liang-jie; Gao, Feng; Li, Jun; Wang, Yu-ming; Gong, Hui-ming; Cheng, Liang

2011-08-01

The authors report a case of functional improvement of the paralyzed diaphragm in high cervical quadriplegia via phrenic nerve neurotization using a functional spinal accessory nerve. Complete spinal cord injury at the C-2 level was diagnosed in a 44-year-old man. Left diaphragm activity was decreased, and the right diaphragm was completely paralyzed. When the level of metabolism or activity (for example, fever, sitting, or speech) slightly increased, dyspnea occurred. The patient underwent neurotization of the right phrenic nerve with the trapezius branch of the right spinal accessory nerve at 11 months postinjury. Four weeks after surgery, training of the synchronous activities of the trapezius muscle and inspiration was conducted. Six months after surgery, motion was observed in the previously paralyzed right diaphragm. The lung function evaluation indicated improvements in vital capacity and tidal volume. This patient was able to sit in a wheelchair and conduct outdoor activities without assisted ventilation 12 months after surgery.

Surgical management of spinal intramedullary tumors: radical and safe strategy for benign tumors.

PubMed

Takami, Toshihiro; Naito, Kentaro; Yamagata, Toru; Ohata, Kenji

2015-01-01

Surgery for spinal intramedullary tumors remains one of the major challenges for neurosurgeons, due to their relative infrequency, unknown natural history, and surgical difficulty. We are sure that safe and precise resection of spinal intramedullary tumors, particularly encapsulated benign tumors, can result in acceptable or satisfactory postoperative outcomes. General surgical concepts and strategies, technical consideration, and functional outcomes after surgery are discussed with illustrative cases of spinal intramedullary benign tumors such as ependymoma, cavernous malformation, and hemangioblastoma. Selection of a posterior median sulcus, posterolateral sulcus, or direct transpial approach was determined based on the preoperative imaging diagnosis and careful inspection of the spinal cord surface. Tumor-cord interface was meticulously delineated in cases of benign encapsulated tumors. Our retrospective functional analysis of 24 consecutive cases of spinal intramedullary ependymoma followed for at least 6 months postoperatively demonstrated a mean grade on the modified McCormick functional schema of 1.8 before surgery, deteriorating significantly to 2.6 early after surgery (< 1 month after surgery), and finally returning to 1.7 in the late postoperative period (> 6 months after surgery). The risk of functional deterioration after surgery should be taken into serious consideration. Functional deterioration after surgery, including neuropathic pain even long after surgery, significantly affects patient quality of life. Better balance between tumor control and functional preservation can be achieved not only by the surgical technique or expertise, but also by intraoperative neurophysiological monitoring, vascular image guidance, and postoperative supportive care. Quality of life after surgery should inarguably be given top priority.

Activity-Based Therapies To Promote Forelimb Use after a Cervical Spinal Cord Injury

PubMed Central

Dai, Haining; MacArthur, Linda; McAtee, Marietta; Hockenbury, Nicole; Tidwell, J. Lille; McHugh, Brian; Mansfield, Kevin; Finn, Tom; Hamers, Frank P.T.

2009-01-01

Abstract Significant interest exists in strategies for improving forelimb function following spinal cord injury. We investigated the effect of enriched housing combined with skilled training on the recovery of skilled and automatic forelimb function after a cervical spinal cord injury in adult rats. All animals were pretrained in skilled reaching, gridwalk crossing, and overground locomotion. Some received a cervical over-hemisection lesion at C4-5, interrupting the right side of the spinal cord and dorsal columns bilaterally, and were housed in standard housing alone or enriched environments with daily training. A subset of animals received rolipram to promote neuronal plasticity. Animals were tested weekly for 4 weeks to measure reaching, errors on the gridwalk, locomotion, and vertical exploration. Biotinylated dextran amine was injected into the cortex to label the corticospinal tract. Enriched environments/daily training significantly increased the number and success of left reaches compared to standard housing. Animals also made fewer errors on the gridwalk, a measure of coordinated forelimb function. However, there were no significant improvements in forelimb use during vertical exploration or locomotion. Likewise, rolipram did not improve any of the behaviors tested. Both enriched housing and rolipram increased plasticity of the corticospinal tract rostral to the lesion. These studies indicate that skilled training after a cervical spinal cord injury improves recovery of skilled forelimb use (reaching) and coordinated limb function (gridwalk) but does not improve automatic forelimb function (locomotion and vertical exploration). These studies suggest that rehabilitating forelimb function after spinal cord injury will require separate strategies for descending and segmental pathways. PMID:19317604

Neuromodulation of the neural circuits controlling the lower urinary tract.

PubMed

Gad, Parag N; Roy, Roland R; Zhong, Hui; Gerasimenko, Yury P; Taccola, Giuliano; Edgerton, V Reggie

2016-11-01

The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner. Copyright © 2016. Published by Elsevier Inc.

International spinal cord injury pulmonary function basic data set.

PubMed

Biering-Sørensen, F; Krassioukov, A; Alexander, M S; Donovan, W; Karlsson, A-K; Mueller, G; Perkash, I; Sheel, A William; Wecht, J; Schilero, G J

2012-06-01

To develop the International Spinal Cord Injury (SCI) Pulmonary Function Basic Data Set within the framework of the International SCI Data Sets in order to facilitate consistent collection and reporting of basic bronchopulmonary findings in the SCI population. International. The SCI Pulmonary Function Data Set was developed by an international working group. The initial data set document was revised on the basis of suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations and societies and individual reviewers. In addition, the data set was posted for 2 months on ISCoS and ASIA websites for comments. The final International SCI Pulmonary Function Data Set contains questions on the pulmonary conditions diagnosed before spinal cord lesion,if available, to be obtained only once; smoking history; pulmonary complications and conditions after the spinal cord lesion, which may be collected at any time. These data include information on pneumonia, asthma, chronic obstructive pulmonary disease and sleep apnea. Current utilization of ventilator assistance including mechanical ventilation, diaphragmatic pacing, phrenic nerve stimulation and Bi-level positive airway pressure can be reported, as well as results from pulmonary function testing includes: forced vital capacity, forced expiratory volume in one second and peak expiratory flow. The complete instructions for data collection and the data sheet itself are freely available on the website of ISCoS (http://www.iscos.org.uk).

Management of bladder dysfunction and satisfaction of life after spinal cord injury in Norway

PubMed Central

Hagen, Ellen Merete; Rekand, Tiina

2014-01-01

Background There is limited knowledge about bladder dysfunction and bladder management in persons with spinal cord injury (SCI) after discharge from the hospital in Norway. The impact of bladder dysfunction on satisfaction of life has been rarely explored. Setting Community-based survey from Norway. Methods An anonymous cross-sectional postal survey. A questionnaire was sent to the registered members of the Norwegian Spinal Cord Injuries Association. A total of 400 participants, with traumatic or non-traumatic SCI, received the questionnaire. Results A total of 248 subjects (62%), 180 men and 68 women, answered the questionnaire. Mean age was 54 years and mean time since injury 13.4 years. A total of 164 participants (66.1%) used intermittent catheterization for bladder emptying (48.5% women versus 72.8% men); more paraplegics than tetraplegics (77.2% versus 55.7%). Recommendations given at the Spinal Cord Units were thoroughly followed by persons who had used catheters more than 5 years. Use of incontinence pads were associated with reduced satisfaction of life. Conclusions The most common method of management of bladder dysfunction is clean intermittent catheterization in Norway. Recommendations were followed more thoroughly by persons who have used intermittent catheterization for more than 5 years. Spinal Cord Units are important source for information and guidance. PMID:24621024

Management of bladder dysfunction and satisfaction of life after spinal cord injury in Norway.

PubMed

Hagen, Ellen Merete; Rekand, Tiina

2014-05-01

There is limited knowledge about bladder dysfunction and bladder management in persons with spinal cord injury (SCI) after discharge from the hospital in Norway. The impact of bladder dysfunction on satisfaction of life has been rarely explored. Community-based survey from Norway. An anonymous cross-sectional postal survey. A questionnaire was sent to the registered members of the Norwegian Spinal Cord Injuries Association. A total of 400 participants, with traumatic or non-traumatic SCI, received the questionnaire. A total of 248 subjects (62%), 180 men and 68 women, answered the questionnaire. Mean age was 54 years and mean time since injury 13.4 years. A total of 164 participants (66.1%) used intermittent catheterization for bladder emptying (48.5% women versus 72.8% men); more paraplegics than tetraplegics (77.2% versus 55.7%). Recommendations given at the Spinal Cord Units were thoroughly followed by persons who had used catheters more than 5 years. Use of incontinence pads were associated with reduced satisfaction of life. The most common method of management of bladder dysfunction is clean intermittent catheterization in Norway. Recommendations were followed more thoroughly by persons who have used intermittent catheterization for more than 5 years. Spinal Cord Units are important source for information and guidance.

Initiation of bladder voiding with epidural stimulation in paralyzed, step trained rats.

PubMed

Gad, Parag N; Roy, Roland R; Zhong, Hui; Lu, Daniel C; Gerasimenko, Yury P; Edgerton, V Reggie

2014-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury.

Initiation of Bladder Voiding with Epidural Stimulation in Paralyzed, Step Trained Rats

PubMed Central

Gad, Parag N.; Roy, Roland R.; Zhong, Hui; Lu, Daniel C.; Gerasimenko, Yury P.; Edgerton, V. Reggie

2014-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury. PMID:25264607

Spinal cord compression in pseudohypoparathyroidism.

PubMed

Roberts, Timothy T; Khasnavis, Siddharth; Papaliodis, Dean N; Citone, Isabella; Carl, Allen L

2013-12-01

Spinal cord compression associated with pseudohypoparathyroidism (PHP) is an increasingly reported sequelae of the underlying metabolic syndrome. The association of neurologic dysfunction with PHP is not well appreciated. We believe this to be secondary to a combination of underlying congenital stenosis, manifest by short pedicles secondary to premature physeal closure, and hypertrophic ossification of the vertebral bony and ligamentous complexes. The purpose of this case report is to review the case of spinal stenosis in a child with PHP Type Ia. We are aware of only eight published reports of patients with PHP Type Ia and spinal stenosis-there are only two previously known cases of pediatric spinal stenosis secondary to PHP. This is a case report detailing the symptoms, diagnosis, interventions, complications, and ultimate outcomes of a pediatric patient undergoing spinal decompression and fusion for symptomatic stenosis secondary to PHP Type Ia. Literature search was reviewed regarding the reports of spinal stenosis and PHP, and the results are culminated and discussed. We report on a 14-year-old obese male with PHP and progressive lower extremity weakness secondary to congenital spinal stenosis. Examination revealed functional upper extremities with spastic paraplegia of bilateral lower extremities. The patient's neurologic function was cautiously monitored, but he deteriorated to a bed-bound state, preoperatively. The patient's chart was reviewed, summarized, and presented. Literature was searched using cross-reference of PHP and the terms "spinal stenosis," "myelopathy", "myelopathic," and "spinal cord compression." All relevant case reports were reviewed, and the results are discussed herein. The patient underwent decompression and instrumented fusion of T2-T11. He improved significantly with regard to lower extremity function, achieving unassisted ambulation function after extensive rehabilitation. Results from surgical decompression in previously reported cases are mixed, ranging from full recovery to iatrogenic paraplegia. The association of neurologic dysfunction with PHP is not well appreciated. It is important to highlight this rare association. Surgical decompression in patients with PHP yields mixed results but may be of greatest efficacy in younger patients who receive early intervention. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparing and contrasting knowledge of pressure ulcer assessment, prevention and management in people with spinal cord injury among nursing staff working in two metropolitan spinal units and rehabilitation medicine training specialists in a three-way comparison.

PubMed

Gupta, N; Loong, B; Leong, G

2012-02-01

To assess for differences in knowledge of pressure ulcer (PU) prevention and management among nurses working in two metropolitan spinal cord injury (SCI) units, and between nurses and rehabilitation registrars (doctors). There is anecdotal evidence of wide variation in PU management. An understanding of current knowledge is fundamental to evidence-based practice implementation. This was a prospective survey, using a multiple choice question format developed with nurse wound specialists. A total of 10 questions assessed PU prevention and 10 assessed management. It was distributed to nurses working at the spinal units and rehabilitation registrars. The results from the groups were analysed for similarities and differences using one- and two-way analysis of variance (ANOVA) tests and tests for significance of specific linear combinations of group means. The response rate was 79% (19/24) and 71% (20/ 28) from the two SCI units, and 46% (13/28) from doctors. Doctors performed better than nurses on prevention questions (P<0.005) but worse on management (P<0.05). There was a significant difference in management knowledge (P<0.001) between nurses working in the two units but not in prevention knowledge (P<0.5) and interestingly years of experience did not correlate with performance (P<0.2 for prevention and P<0.5 for management questions). Rehabilitation registrars score better in prevention questions, but poorer in management questions, which reflects academic rather than experiential knowledge. There are also differences in management knowledge among nurses, based on work area rather than years of experience. Although knowledge does not necessarily reflect practice, this calls for better standardisation and implementation of wound management pathways.

Functional MR imaging of the spinal cord in cervical spinal cord injury patients by acupuncture at LI 4 (Hegu) and LI 11(Quchi).

PubMed

Chen, Y X; Kong, K M; Wang, W D; Xie, C H; Wu, R H

2007-01-01

To investigate the cervical spinal cord mapping on acupuncture at LI 4 (Hegu) and LI 11 (Quchi) by using 'Signal Enhancement by Extravascular water Protons' (SEEP)-fMRI, and to establish the response of using acupuncture in the cervical spinal cord. This research may provide some laboratory evidences from the acupuncture treatment on the cervical spinal cord of injuried patients. Seven healthy volunteers (healthy group) and three cervical spinal cord injury patients (injury group) were underwent low-frequency electrical stimulation at LI 4 and LI 11. Meanwhile, a single-shot fast spin-echo (SSFSE) sequence was used to perform functional MR imaging on a 1.5 T GE Signa MR system. The signals from the cervical spinal cord activated was measured both in sagittal and transverse imaging planes and then analyzed by AFNI (Analysis of Functional Neuroimages) system. It was found that in the sagittal view, two groups had an fMRI response in the cervical spinal cord after given acupuncture treatments at LI 4 and LI 11. The localizations of the segmental fMRI activation were focused at C6 and C2 cervical spinal cord level. In the transverse imaging plane, significant fMRI responses could be measured from the four of seven healthy volunteers and from two of three cervical spinal cord injury patients. They were located at C6/7 segments. The cross-sectional localization of the activity measured in the spinal cord was most in terms of the ipsilateral posterior direction. The signal amplitude varied mainly between 6.8%17.8%. However, the difference found between the two groups had no statistical meaning. The fMRI technique had detected an activation focused at C6 and C2 cervical spinal cord levels by use of acupuncture at LI 4 and LI 11 on a 1.5T GE clinical system. This proved that the meridians and points are found to be in existence. The fMRI can be used as a harmless research method to discuss the mechanisms of acupuncture as well as study the mechanisms of spinal cord diseases. It can be used to direct or monitor the related therapy on the spinal cord injury patients.

Management of chronic spinal cord dysfunction.

PubMed

Abrams, Gary M; Ganguly, Karunesh

2015-02-01

Both acute and chronic spinal cord disorders present multisystem management problems to the clinician. This article highlights key issues associated with chronic spinal cord dysfunction. Advances in symptomatic management for chronic spinal cord dysfunction include use of botulinum toxin to manage detrusor hyperreflexia, pregabalin for management of neuropathic pain, and intensive locomotor training for improved walking ability in incomplete spinal cord injuries. The care of spinal cord dysfunction has advanced significantly over the past 2 decades. Management and treatment of neurologic and non-neurologic complications of chronic myelopathies ensure that each patient will be able to maximize their functional independence and quality of life.

Cannabidiol-treated rats exhibited higher motor score after cryogenic spinal cord injury.

PubMed

Kwiatkoski, Marcelo; Guimarães, Francisco Silveira; Del-Bel, Elaine

2012-04-01

Cannabidiol (CBD), a non-psychoactive constituent of cannabis, has been reported to induce neuroprotective effects in several experimental models of brain injury. We aimed at investigating whether this drug could also improve locomotor recovery of rats submitted to spinal cord cryoinjury. Rats were distributed into five experimental groups. Animals were submitted to laminectomy in vertebral segment T10 followed or not by application of liquid nitrogen for 5 s into the spinal cord at the same level to cause cryoinjury. The animals received injections of vehicle or CBD (20 mg/kg) immediately before, 3 h after and daily for 6 days after surgery. The Basso, Beattie, and Bresnahan motor evaluation test was used to assess motor function post-lesion one day before surgery and on the first, third, and seventh postoperative days. The extent of injury was evaluated by hematoxylin-eosin histology and FosB expression. Cryogenic lesion of the spinal cord resulted in a significant motor deficit. Cannabidiol-treated rats exhibited a higher Basso, Beattie, and Bresnahan locomotor score at the end of the first week after spinal cord injury: lesion + vehicle, day 1: zero, day 7: four, and lesion + Cannabidiol 20 mg/kg, day 1: zero, day 7: seven. Moreover, at this moment there was a significant reduction in the extent of tissue injury and FosB expression in the ventral horn of the spinal cord. The present study confirmed that application of liquid nitrogen to the spinal cord induces reproducible and quantifiable spinal cord injury associated with locomotor function impairments. Cannabidiol improved locomotor functional recovery and reduced injury extent, suggesting that it could be useful in the treatment of spinal cord lesions.

Mesenchymal Stem Cell-Based Therapy Improves Lower Limb Movement After Spinal Cord Ischemia in Rats.

PubMed

Takahashi, Shinya; Nakagawa, Kei; Tomiyasu, Mayumi; Nakashima, Ayumu; Katayama, Keijiro; Imura, Takeshi; Herlambang, Bagus; Okubo, Tomoe; Arihiro, Koji; Kawahara, Yumi; Yuge, Louis; Sueda, Taijiro

2018-05-01

Spinal cord ischemia is a devastating complication after thoracic and thoracoabdominal aortic operations. In this study, we aimed to investigate the effects of mesenchymal stem cells (MSCs), which have regenerative capability and exert paracrine actions on damaged tissues, injected into rat models of spinal cord ischemia-reperfusion injury. Forty-five Sprague-Dawley rats were divided into sham, phosphate-buffered saline (PBS), and MSC groups. Spinal cord ischemia was induced in the latter two groups by balloon occlusion of the thoracic aorta. MSCs and PBS were then immediately injected into the left carotid artery of the MSC and PBS groups, respectively. Hindlimb motor function was evaluated at 6 and 24 hours. The spinal cord was removed at 24 hours after ischemia-reperfusion injury, and histologic and immunohistochemical analyses and real-time polymerase chain reaction assessments were performed. Rats in the MSC and PBS groups showed flaccid paraparesis/paraplegia postoperatively. Hindlimb function was significantly better at 6 and 24 hours after ischemia-reperfusion injury in the MSC group than in the PBS group (p < 0.05). The number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive neuron cells in the spinal cord and the ratio of Bax to Bcl2 were significantly larger (p < 0.05) in the PBS group than in the MSC group. The injected MSCs were observed in the spinal cord 24 hours after ischemia-reperfusion injury. The MSC therapy by transarterial injection immediately after spinal cord ischemia-reperfusion injury may improve lower limb function by preventing apoptosis of neuron cells in the spinal cord. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Identification of the sexually dimorphic gastrin-releasing peptide system in the lumbosacral spinal cord that controls male reproductive function in the mouse and Asian house musk shrew (Suncus murinus).

PubMed

Tamura, Kei; Kobayashi, Yasuhisa; Hirooka, Asuka; Takanami, Keiko; Oti, Takumi; Jogahara, Takamichi; Oda, Sen-Ichi; Sakamoto, Tatsuya; Sakamoto, Hirotaka

2017-05-01

Several regions of the brain and spinal cord control male reproductive function. We previously demonstrated that the gastrin-releasing peptide (GRP) system, located in the lumbosacral spinal cord of rats, controls spinal centers to promote penile reflexes during male copulatory behavior. However, little information exists on the male-specific spinal GRP system in animals other than rats. The objective of this study was to examine the functional generality of the spinal GRP system in mammals using the Asian house musk shrew (Suncus murinus; suncus named as the laboratory strain), a specialized placental mammal model. Mice are also used for a representative model of small laboratory animals. We first isolated complementary DNA encoding GRP in suncus. Phylogenetic analysis revealed that suncus preproGRP was clustered to an independent branch. Reverse transcription-PCR showed that GRP and its receptor mRNAs were both expressed in the lumbar spinal cord of suncus and mice. Immunohistochemistry for GRP demonstrated that the sexually dimorphic GRP system and male-specific expression/distribution patterns of GRP in the lumbosacral spinal cord in suncus are similar to those of mice. In suncus, we further found that most GRP-expressing neurons in males also express androgen receptors, suggesting that this male-dominant system in suncus is also androgen-dependent. Taken together, these results indicate that the sexually dimorphic spinal GRP system exists not only in mice but also in suncus, suggesting that this system is a conserved property in mammals. J. Comp. Neurol. 525:1586-1598, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Osteogenesis imperfecta in childhood: effects of spondylodesis on functional ability, ambulation and perceived competence.

PubMed

Tolboom, N; Cats, E A; Helders, P J M; Pruijs, J E H; Engelbert, R H H

2004-03-01

We studied the effects of spondylodesis on spinal curvature, functional outcome, level of ambulation and perceived competence in 11 children with osteogenesis imperfecta (OI). Mean age at surgical intervention was 13.1 years (SD 2.5 years) and follow-up amounted to 3.4 years (SD 2.3 years). Spinal curvature was measured according to Cobb. The level of ambulation was scored according to the modified criteria of Bleck. Functional abilities and the amount of parental assistance were scored using the Dutch version of the Pediatric Evaluation of Disability Inventory (PEDI). Perceived competence was measured using the Harter Self-Perception Profile for Children. The amount of fatigue, spinal pain and presence of subjective dyspnea were scored with a visual analog scale. The median progression per year before spondylodesis was 6.1 degrees (interquartile range 2.9 degrees -12.9 degrees ) and after the spondylodesis it was 5.0 degrees (interquartile range 1.6 degrees -11.0 degrees ). No significant progression or regression in the level of ambulation was found. Perceived competence improved slightly. In the total score of the perceived competence, a borderline significant increase was found ( P-value 0.068). We concluded that spinal fusion in children with OI does not materially influence functional ability and level of ambulation. Self-perceived competence seemed to improve after surgery. The amount of pain, fatigue and subjective dyspnea seemed to diminish after spinal surgery. Progression of scoliosis proceeded, as did development of spinal curvature at the junction of the spondylodesis. Therefore, oral or intravenous bisphosphonates before and after spinal surgery should be considered.

Magnetic resonance imaging features of dogs with incomplete recovery after acute, severe spinal cord injury

PubMed Central

Lewis, Melissa J.; Cohen, Eli B.; Olby, Natasha J.

2017-01-01

Study Design Retrospective case series Objectives Describe the magnetic resonance imaging (MRI) features of dogs chronically impaired after severe spinal cord injury (SCI) and investigate associations between imaging variables and residual motor function. Setting United States of America Methods Thoracolumbar MRI from dogs with incomplete recovery months to years after clinically complete (paralysis with loss of pain perception) thoracolumbar SCI were reviewed. Lesion features were described and quantified. Gait was quantified using an ordinal, open field scale (OFS). Associations between imaging features and gait scores, duration of injury (DOI) or SCI treatment were determined. Results 35 dogs were included. Median OFS was 2 (0–6), median DOI was 13 months (3–83) and intervertebral disc herniation was the most common diagnosis (n=27). Myelomalacia was the most common qualitative feature followed by cystic change; syringomyelia and fibrosis were uncommon. Lesion length corrected to L2 length (LL:L2) was variable (median LL:L2=3.5 (1.34–11.54)). Twenty-nine dogs had 100% maximum cross-sectional spinal cord compromise (MSCC) at the lesion epicenter and the length of 100% compromised area varied widely (median length 100% MSCC:L2=1.29 (0.39–7.64). Length 100% MSCC:L2 was associated with OFS (p=0.012). OFS was not associated with any qualitative features. DOI or treatment type were not associated with imaging features or lesion quantification. Conclusions Lesion characteristics on MRI in dogs with incomplete recovery after severe SCI were established. Length of 100% MSCC was associated with hind limb motor function. Findings demonstrate a spectrum of injury severity on MRI amongst severely affected dogs which is related to functional status. PMID:29057987

63 FR 47026 - Proposed Vaccine Information Materials for Hepatitis B, Haemophilus influenzae type b (Hib...

Federal Register 2010, 2011, 2012, 2013, 2014

1998-09-03

... United States. Meningitis is an infection of the brain and spinal cord coverings which can lead to..., meningitis (infection of the brain and spinal cord covering), painful swelling of the testicles, and, rarely... Vaccine Information Materials for Hepatitis B, Haemophilus influenzae type b (Hib), Varicella (Chickenpox...

In vitro and in vivo analysis and characterization of engineered spinal neural implants (Conference Presentation)

NASA Astrophysics Data System (ADS)

Shor, Erez; Shoham, Shy; Levenberg, Shulamit

2016-03-01

Spinal cord injury is a devastating medical condition. Recent developments in pre-clinical and clinical research have started to yield neural implants inducing functional recovery after spinal cord transection injury. However, the functional performance of the transplants was assessed using histology and behavioral experiments which are unable to study cell dynamics and the therapeutic response. Here, we use neurophotonic tools and optogenetic probes to investigate cellular level morphology and activity characteristics of neural implants over time at the cellular level. These methods were used in-vitro and in-vivo, in a mouse spinal cord injury implant model. Following previous attempts to induce recovery after spinal cord injury, we engineered a pre-vascularized implant to obtain better functional performance. To image network activity of a construct implanted in a mouse spinal cord, we transfected the implant to express GCaMP6 calcium activity indicators and implanted these constructs under a spinal cord chamber enabling 2-photon chronic in vivo neural activity imaging. Activity and morphology analysis image processing software was developed to automatically quantify the behavior of the neural and vascular networks. Our experimental results and analyses demonstrate that vascularized and non-vascularized constructs exhibit very different morphologic and activity patterns at the cellular level. This work enables further optimization of neural implants and also provides valuable tools for continuous cellular level monitoring and evaluation of transplants designed for various neurodegenerative disease models.

[Exoskeletons for rehabilitation of patients with spinal cord injuries. Options and limitations].

PubMed

Aach, M; Meindl, R C; Geßmann, J; Schildhauer, T A; Citak, M; Cruciger, O

2015-02-01

Mobile exoskeletons are increasingly being applied in the course of rehabilitation and provision of medical aids to patients with spinal cord injuries. This article gives a description of the currently available exoskeletal systems and the clinical application including scientific and medical evidence, to derive recommendations regarding clinical practice of the various exoskeletons in the rehabilitation of patients with spinal cord injuries. The different systems represent a useful adjunct to the therapeutic regimen depending on the medical objectives. Posture-controlled exoskeletons in particular enable mobilization of patients with neurological gait disorders via direct motion support. In addition the neurologically controlled exoskeleton HAL® leads to functional improvements in patients with residual muscular functions in the chronic phase of spinal cord injury in terms of improved walking abilities subsequent to training. However, beneficial effects on bone density, bladder function and perfusion are conceivable but not yet adequately supported by evidence. Positive effects on spasticity and neuropathic pain are currently based only on case series or small clinical trials. Although exoskeletons are not yet an established tool in the treatment of spinal cord injuries, the systems will play a more important role in rehabilitation of patients with spinal cord injuries in the future. Neurologically controlled exoskeletons show beneficial effects in the treatment of acute and chronic spinal cord injuries and might therefore evolve to be a useful alternative to conventional locomotion training.

Motor Control of Human Spinal Cord Disconnected from the Brain and Under External Movement.

PubMed

Mayr, Winfried; Krenn, Matthias; Dimitrijevic, Milan R

2016-01-01

Motor control after spinal cord injury is strongly depending on residual ascending and descending pathways across the lesion. The individually altered neurophysiology is in general based on still intact sublesional control loops with afferent sensory inputs linked via interneuron networks to efferent motor outputs. Partial or total loss of translesional control inputs reduces and alters the ability to perform voluntary movements and results in motor incomplete (residual voluntary control of movement functions) or motor complete (no residual voluntary control) spinal cord injury classification. Of particular importance are intact functionally silent neural structures with residual brain influence but reduced state of excitability that inhibits execution of voluntary movements. The condition is described by the term discomplete spinal cord injury. There are strong evidences that artificial afferent input, e.g., by epidural or noninvasive electrical stimulation of the lumbar posterior roots, can elevate the state of excitability and thus re-enable or augment voluntary movement functions. This modality can serve as a powerful assessment technique for monitoring details of the residual function profile after spinal cord injury, as a therapeutic tool for support of restoration of movement programs and as a neuroprosthesis component augmenting and restoring movement functions, per se or in synergy with classical neuromuscular or muscular electrical stimulation.

CD8+ T Cells Cause Disability and Axon Loss in a Mouse Model of Multiple Sclerosis

PubMed Central

Schmalstieg, William F.; Sauer, Brian M.; Wang, Huan; German, Christopher L.; Windebank, Anthony J.; Rodriguez, Moses; Howe, Charles L.

2010-01-01

Background The objective of this study was to test the hypothesis that CD8+ T cells directly mediate motor disability and axon injury in the demyelinated central nervous system. We have previously observed that genetic deletion of the CD8+ T cell effector molecule perforin leads to preservation of motor function and preservation of spinal axons in chronically demyelinated mice. Methodology/Principal Findings To determine if CD8+ T cells are necessary and sufficient to directly injure demyelinated axons, we adoptively transferred purified perforin-competent CD8+ spinal cord-infiltrating T cells into profoundly demyelinated but functionally preserved perforin-deficient host mice. Transfer of CD8+ spinal cord-infiltrating T cells rapidly and irreversibly impaired motor function, disrupted spinal cord motor conduction, and reduced the number of medium- and large-caliber spinal axons. Likewise, immunodepletion of CD8+ T cells from chronically demyelinated wildtype mice preserved motor function and limited axon loss without altering other disease parameters. Conclusions/Significance In multiple sclerosis patients, CD8+ T cells outnumber CD4+ T cells in active lesions and the number of CD8+ T cells correlates with the extent of ongoing axon injury and functional disability. Our findings suggest that CD8+ T cells may directly injure demyelinated axons and are therefore a viable therapeutic target to protect axons and motor function in patients with multiple sclerosis. PMID:20814579

Prevalence and Causes of Paralysis-United States, 2013.

PubMed

Armour, Brian S; Courtney-Long, Elizabeth A; Fox, Michael H; Fredine, Heidi; Cahill, Anthony

2016-10-01

To estimate the prevalence and causes of functional paralysis in the United States. We used the 2013 US Paralysis Prevalence & Health Disparities Survey to estimate the prevalence of paralysis, its causes, associated sociodemographic characteristics, and health effects among this population. Nearly 5.4 million persons live with paralysis. Most persons with paralysis were younger than 65 years (72.1%), female (51.7%), White (71.4%), high school graduates (64.8%), married or living with a partner (47.4%), and unable to work (41.8%). Stroke is the leading cause of paralysis, affecting 33.7% of the population with paralysis, followed by spinal cord injury (27.3%), multiple sclerosis (18.6%), and cerebral palsy (8.3%). According to the functional definition, persons living with paralysis represent a large segment of the US population, and two thirds of them are between ages 18 and 64 years. Targeted health promotion that uses inclusion strategies to account for functional limitations related to paralysis can be undertaken in partnership with state and local health departments.

White matter organization in cervical spinal cord relates differently to age and control of grip force in healthy subjects.

PubMed

Lindberg, Påvel G; Feydy, Antoine; Maier, Marc A

2010-03-17

Diffusion tensor imaging (DTI) can be used to elucidate relations between CNS structure and function. We hypothesized that the degree of spinal white matter organization relates to the accuracy of control of grip force. Healthy subjects of different age were studied using DTI and visuomotor tracking of precision grip force. The latter is a prime component of manual dexterity. A regional analysis of spinal white matter [fractional anisotropy (FA)] across multiple cervical levels (C2-C3, C4-C5, and C6-C7) and in different regions of interest (left and right lateral or medial spinal cord) was performed. FA was highest at the C2-C3 level, higher on the right than the left side, and higher in the lateral than in the medial spinal cord (p < 0.001). FA of whole cervical spinal cord (C2-C7) was lower in subjects with high tracking error (r = -0.56, p = 0.004) and decreased with age (r = -0.63, p = 0.001). A multiple regression analysis revealed an independent contribution of each predictor (semipartial correlations: age, r = -0.55, p < 0.001; tracking error, r = -0.49, p = 0.003). The closest relation between FA and tracking error was found at the C6-C7 level in the lateral spinal cord, in which the corticospinal tract innervates spinal circuitry controlling hand and digit muscles. FA of the medial spinal cord correlated consistently with age across all cervical levels, whereas FA of the lateral spinal cord did not. The results suggest (1) a functionally relevant specialization of lateral spinal cord white matter and (2) an increased sensitivity to age-related decline in medial spinal cord white matter in healthy subjects.

Functional magnetic resonance imaging of the human spinal cord during vibration stimulation of different dermatomes.

PubMed

Lawrence, Jane M; Stroman, Patrick W; Kollias, Spyros S

2008-03-01

We investigated noninvasively areas of the healthy human spinal cord that become active in response to vibration stimulation of different dermatomes using functional magnetic resonance imaging (fMRI). The objectives of this study were to: (1) examine the patterns of consistent activity in the spinal cord during vibration stimulation of the skin, and (2) investigate the rostrocaudal distribution of active pixels when stimulation was applied to different dermatomes. FMRI of the cervical and lumbar spinal cord of seven healthy human subjects was carried out during vibration stimulation of six different dermatomes. In separate experiments, vibratory stimulation (about 50 Hz) was applied to the right biceps, wrist, palm, patella, Achilles tendon and left palm. The segmental distribution of activity observed by fMRI corresponded well with known spinal cord neuroanatomy. The peak number of active pixels was observed at the expected level of the spinal cord with some activity in the adjacent segments. The rostrocaudal distribution of activity was observed to correspond to the dermatome being stimulated. Cross-sectional localization of activity was primarily in dorsal areas but also spread into ventral and intermediate areas of the gray matter and a distinct laterality ipsilateral to the stimulated limb was not observed. We demonstrated that fMRI can detect a dermatome-dependent pattern of spinal cord activity during vibratory stimulation and can be used as a passive stimulus for the noninvasive assessment of the functional integrity of the human spinal cord. Demonstration of cross-sectional selectivity of the activation awaits further methodological and experimental refinements.

Spine and Spinal Cord Injuries After Falls From Tree Stands During the Wisconsin Deer Hunting Season.

PubMed

Hamilton, Kimberly; Rocque, Brandon; Brooks, Nathaniel

2017-11-01

Deer hunting is popular in much of the United States. In Wisconsin, use of tree stands for hunting is common. Spine surgeons at a Level 1 Trauma Center observed a high incidence of spine and spinal cord injury due to falls from tree stands while hunting. This study's purpose is to systematically characterize and classify those injuries. We reviewed the University of Wisconsin Hospital and Clinics' trauma database for tree stand-related injuries from 1999 to 2013. We collected and analyzed data pertaining to hunters' demographics, comorbidities, type and mechanism of injury, injury severity, and management. We identified 117 patients evaluated after a tree stand fall. Sixty-five (ages 16-76) suffered spine fractures that occurred at all levels, from occipital condyle to sacrum, with thoracolumbar compression and burst fractures being most common. Fractures occurred in the following locations: cranio-cervical junction (8.7%), cervical spine (7.6%), cervical-thoracic junction (6.5%), thoracic spine (32.6%), thoracolumbar junction (33.7%), and lumbar spine (10.9%). Twenty-one patients (32%) experienced a single spinal fracture; 44 patients (68%) suffered multiple spinal fractures. Twenty-five patients (38%) required surgical fixation; 19 patients experienced loss of neurologic function: 5 complete spinal cord injuries (SCI), 5 incomplete SCI, 2 central cord syndromes, and 8 radiculopathies. Two mortalities, both of cardiopulmonary etiology, were noted-one in a patient without a spine fracture and the other in a patient with a complete spinal cord injury at T4. The majority of spine fractures are treated nonoperatively. However, enough patients require surgical intervention that consultation with a neurosurgical or orthopedic spine surgeon is prudent. It is more common to have multiple spine fractures from a tree stand fall, therefore, it is recommended that if 1 fracture is identified the entire spine be evaluated for additional fractures. For safety, it is recommended that hunters wear and use safety harnesses appropriately. Additionally, keeping the height of the tree stand at 10 feet or less is associated with a lower likelihood of spinal cord injury. Further study is needed to determine additional interventions such as education that might reduce the injury frequency in this population.

Effect of spinal manipulation on the development of history-dependent responsiveness of lumbar paraspinal muscle spindles in the cat

PubMed Central

Cao, Dong-Yuan; Pickar, Joel G.

2014-01-01

We determined whether spinal manipulation could prevent and/or reverse the decrease and increase in paraspinal muscle spindle responsiveness caused respectively by lengthening and shortening histories of the lumbar muscles. Single unit spindle activity from multifidus and longissimus muscles was recorded in the L6 dorsal root in anesthetized cats. Muscle history was created and spinal manipulation delivered (thrust amplitude: 1.0mm, duration: 100ms) using a feedback-controlled motor attached to the L6 spinous process. Muscle spindle discharge to a fixed vertebral position (static test) and to vertebral movement (dynamic test) was evaluated following the lengthening and shortening histories. For the static test, changes in muscle spindle responsiveness were significantly less when spinal manipulation followed muscle history (p<0.01), but not when spinal manipulation preceded it (p>0.05). For the dynamic test, spinal manipulation did not significantly affect the history-induced change in muscle spindle responsiveness. Spinal manipulation may partially reverse the effects of muscle history on muscle spindle signaling of vertebral position. PMID:24932019

Twiddler's syndrome in spinal cord stimulation.

PubMed

Al-Mahfoudh, Rafid; Chan, Yuen; Chong, Hsu Pheen; Farah, Jibril Osman

2016-01-01

The aims are to present a case series of Twiddler's syndrome in spinal cord stimulators with analysis of the possible mechanism of this syndrome and discuss how this phenomenon can be prevented. Data were collected retrospectively between 2007 and 2013 for all patients presenting with failure of spinal cord stimulators. The diagnostic criterion for Twiddler's syndrome is radiological evidence of twisting of wires in the presence of failure of spinal cord stimulation. Our unit implants on average 110 spinal cord stimulators a year. Over the 5-year study period, all consecutive cases of spinal cord stimulation failure were studied. Three patients with Twiddler's syndrome were identified. Presentation ranged from 4 to 228 weeks after implantation. Imaging revealed repeated rotations and twisting of the wires of the spinal cord stimulators leading to hardware failure. To the best of our knowledge this is the first reported series of Twiddler's syndrome with implantable pulse generators (IPGs) for spinal cord stimulation. Hardware failure is not uncommon in spinal cord stimulation. Awareness and identification of Twiddler's syndrome may help prevent its occurrence and further revisions. This may be achieved by implanting the IPG in the lumbar region subcutaneously above the belt line. Psychological intervention may have a preventative role for those who are deemed at high risk of Twiddler's syndrome from initial psychological screening.

"Low-intensity laser therapy effect on the recovery of traumatic spinal cord injury".

PubMed

Paula, Alecsandra Araujo; Nicolau, Renata Amadei; Lima, Mario de Oliveira; Salgado, Miguel Angel Castillo; Cogo, José Carlos

2014-11-01

Scientific advances have been made to optimize the healing process in spinal cord injury. Studies have been developed to obtain effective treatments in controlling the secondary injury that occurs after spinal cord injury, which substantially changes the prognosis. Low-intensity laser therapy (LILT) has been applied in neuroscience due to its anti-inflammatory effects on biological tissue in the repairing process. Few studies have been made associating LILT to the spinal cord injury. The objective of this study was to investigate the effect of the LILT (GaAlAs laser-780 nm) on the locomotor functional recovery, histomorphometric, and histopathological changes of the spinal cord after moderate traumatic injury in rats (spinal cord injury at T9 and T10). Thirty-one adult Wistar rats were used, which were divided into seven groups: control without surgery (n = 3), control surgery (n = 3), laser 6 h after surgery (n = 5), laser 48 h after surgery (n = 5), medullar lesion (n = 5) without phototherapy, medullar lesion + laser 6 h after surgery (n = 5), and medullar lesion + laser 48 h after surgery (n = 5). The assessment of the motor function was performed using Basso, Beattie, and Bresnahan (BBB) scale and adapted Sciatic Functional Index (aSFI). The assessment of urinary dysfunction was clinically performed. After 21 days postoperative, the animals were euthanized for histological and histomorphometric analysis of the spinal cord. The results showed faster motor evolution in rats with spinal contusion treated with LILT, maintenance of the effectiveness of the urinary system, and preservation of nerve tissue in the lesion area, with a notorious inflammation control and increased number of nerve cells and connections. In conclusion, positive effects on spinal cord recovery after moderate traumatic spinal cord injury were shown after LILT.

Robot-Assisted Training of Arm and Hand Movement Shows Functional Improvements for Incomplete Cervical Spinal Cord Injury.

PubMed

Francisco, Gerard E; Yozbatiran, Nuray; Berliner, Jeffrey; OʼMalley, Marcia K; Pehlivan, Ali Utku; Kadivar, Zahra; Fitle, Kyle; Boake, Corwin

2017-10-01

The aim of the study was to demonstrate the feasibility, tolerability, and effectiveness of robotic-assisted arm training in incomplete chronic tetraplegia. Pretest/posttest/follow-up was conducted. Ten individuals with chronic cervical spinal cord injury were enrolled. Participants performed single degree-of-freedom exercise of upper limbs at an intensity of 3-hr per session for 3 times a week for 4 wks with MAHI Exo-II. Arm and hand function tests (Jebsen-Taylor Hand Function Test, Action Research Arm Test), strength of upper limb (upper limb motor score, grip, and pinch strength), and independence in daily living activities (Spinal Cord Independence Measure II) were performed at baseline, end of training, and 6 mos later. After 12 sessions of training, improvements in arm and hand functions were observed. Jebsen-Taylor Hand Function Test (0.14[0.04]-0.21[0.07] items/sec, P = 0.04), Action Research Arm Test (30.7[3.8]-34.3[4], P = 0.02), American Spinal Injury Association upper limb motor score (31.5[2.3]-34[2.3], P = 0.04) grip (9.7[3.8]-12[4.3] lb, P = 0.02), and pinch strength (4.5[1.1]-5.7[1.2] lb, P = 0.01) resulted in significant increases. Some gains were maintained at 6 mos. No change in Spinal Cord Independence Measure II scores and no adverse events were observed. Results from this pilot study suggest that repetitive training of arm movements with MAHI Exo-II exoskeleton is safe and has potential to be an adjunct treatment modality in rehabilitation of persons with spinal cord injury with mild to moderate impaired arm functions.

The Effect of Spinal Tap Test on Different Sensory Modalities of Postural Stability in Idiopathic Normal Pressure Hydrocephalus.

PubMed

Abram, Katrin; Bohne, Silvia; Bublak, Peter; Karvouniari, Panagiota; Klingner, Carsten M; Witte, Otto W; Guntinas-Lichius, Orlando; Axer, Hubertus

2016-01-01

Postural instability in patients with normal pressure hydrocephalus (NPH) is a most crucial symptom leading to falls with secondary complications. The aim of the current study was to evaluate the therapeutic effect of spinal tap on postural stability in these patients. Seventeen patients with clinical symptoms of NPH were examined using gait scale, computerized dynamic posturography (CDP), and neuropsychological assessment. Examinations were done before and after spinal tap test. The gait score showed a significant improvement 24 h after spinal tap test in all subtests and in the sum score (p < 0.003), while neuropsychological assessment did not reveal significant differences 72 h after spinal tap test. CDP showed significant improvements after spinal tap test in the Sensory Organization Tests 2 (p = 0.017), 4 (p = 0.001), and 5 (p = 0.009) and the composite score (p = 0.01). Patients showed best performance in somatosensory and worst performance in vestibular dominated tests. Vestibular dominated tests did not improve significantly after spinal tap test, while somatosensory and visual dominated tests did. Postural stability in NPH is predominantly affected by deficient vestibular functions, which did not improve after spinal tap test. Conditions which improved best were mainly independent from visual control and are based on proprioceptive functions.

Intrathecal oxybuprocaine and proxymetacaine produced potent and long-lasting spinal anesthesia in rats.

PubMed

Hung, Ching-Hsia; Wang, Jhi-Joung; Chen, Yu-Chung; Chu, Chin-Chen; Chen, Yu-Wen

2009-05-01

Proxymetacaine and oxybuprocaine were clinically used for topical ocular anesthesia but never for spinal anesthesia, and therefore spinal anesthetic effects of proxymetacaine and oxybuprocaine were performed and compared with bupivacaine and lidocaine. After rats were injected intrathecally with proxymetacaine, oxybuprocaine, bupivacaine, and lidocane, dose-response curves were constructed. We evaluated the potencies (ED(50)) and durations (time to full recovery) of proxymetacaine and oxybuprocaine on spinal blockades of motor function, proprioception, and nociception and compared with bupivacaine and lidocaine in rats. We found that proxymetacaine and oxybuprocaine acted like bupivacaine or lidocaine and produced dose-related spinal blockades of motor function, proprioception and nociception. On the ED(50) basis, the ranks of potencies in motor, proprioception, and nociception were proxymetacaine>oxybuprocaine>bupivacaine>lidocaine (P<0.01 for the differences). On an equipotent basis (ED(20), ED(50), ED(80)), oxybuprocaine and bupivacaine produced similarly longer spinal blockades than did proxymetacaine or lidocaine (P<0.05 for the differences). Intrathecal proxymetacaine, oxybuprocaine, and bupivacaine also produced longer sensory blockade than motor blockade. These data demonstrated that oxybuprocaine and proxymetacaine produced more potent spinal blockades, when compared with bupivacaine or lidocaine. Oxybuprocaine and bupivacaine with a more sensory-selective action over motor blockade produced longer spinal blockade than did proxymetacaine or lidocaine.

The use of regression tree analysis for predicting the functional outcome following traumatic spinal cord injury.

PubMed

Facchinello, Yann; Beauséjour, Marie; Richard-Denis, Andreane; Thompson, Cynthia; Mac-Thiong, Jean-Marc

2017-10-25

Predicting the long-term functional outcome following traumatic spinal cord injury is needed to adapt medical strategies and to plan an optimized rehabilitation. This study investigates the use of regression tree for the development of predictive models based on acute clinical and demographic predictors. This prospective study was performed on 172 patients hospitalized following traumatic spinal cord injury. Functional outcome was quantified using the Spinal Cord Independence Measure collected within the first-year post injury. Age, delay prior to surgery and Injury Severity Score were considered as continuous predictors while energy of injury, trauma mechanisms, neurological level of injury, injury severity, occurrence of early spasticity, urinary tract infection, pressure ulcer and pneumonia were coded as categorical inputs. A simplified model was built using only injury severity, neurological level, energy and age as predictor and was compared to a more complex model considering all 11 predictors mentioned above The models built using 4 and 11 predictors were found to explain 51.4% and 62.3% of the variance of the Spinal Cord Independence Measure total score after validation, respectively. The severity of the neurological deficit at admission was found to be the most important predictor. Other important predictors were the Injury Severity Score, age, neurological level and delay prior to surgery. Regression trees offer promising performances for predicting the functional outcome after a traumatic spinal cord injury. It could help to determine the number and type of predictors leading to a prediction model of the functional outcome that can be used clinically in the future.

NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury.

PubMed

Rao, Jia-Sheng; Zhao, Can; Zhang, Aifeng; Duan, Hongmei; Hao, Peng; Wei, Rui-Han; Shang, Junkui; Zhao, Wen; Liu, Zuxiang; Yu, Juehua; Fan, Kevin S; Tian, Zhaolong; He, Qihua; Song, Wei; Yang, Zhaoyang; Sun, Yi Eve; Li, Xiaoguang

2018-06-12

Spinal cord injury (SCI) often leads to permanent loss of motor, sensory, and autonomic functions. We have previously shown that neurotrophin3 (NT3)-loaded chitosan biodegradable material allowed for prolonged slow release of NT3 for 14 weeks under physiological conditions. Here we report that NT3-loaded chitosan, when inserted into a 1-cm gap of hemisectioned and excised adult rhesus monkey thoracic spinal cord, elicited robust axonal regeneration. Labeling of cortical motor neurons indicated motor axons in the corticospinal tract not only entered the injury site within the biomaterial but also grew across the 1-cm-long lesion area and into the distal spinal cord. Through a combination of magnetic resonance diffusion tensor imaging, functional MRI, electrophysiology, and kinematics-based quantitative walking behavioral analyses, we demonstrated that NT3-chitosan enabled robust neural regeneration accompanied by motor and sensory functional recovery. Given that monkeys and humans share similar genetics and physiology, our method is likely translatable to human SCI repair.

The spinal cord: a review of functional neuroanatomy.

PubMed

Bican, Orhan; Minagar, Alireza; Pruitt, Amy A

2013-02-01

The spinal cord controls the voluntary muscles of the trunk and limbs and receives sensory input from these areas. It extends from the medulla oblongata to the lower border of the first lumbar vertebra. A basic knowledge of spinal cord anatomy is essential for interpretation of clinical signs and symptoms and for understanding of pathologic processes involving the spinal cord. In this article, anatomic structures are correlated with relevant clinical signs and symptoms and a step-wise approach to spinal cord diagnosis is outlined. Copyright © 2013 Elsevier Inc. All rights reserved.

Therapeutic intraspinal stimulation to generate activity and promote long-term recovery.

PubMed

Mondello, Sarah E; Kasten, Michael R; Horner, Philip J; Moritz, Chet T

2014-01-01

Neuroprosthetic approaches have tremendous potential for the treatment of injuries to the brain and spinal cord by inducing appropriate neural activity in otherwise disordered circuits. Substantial work has demonstrated that stimulation applied to both the central and peripheral nervous system leads to immediate and in some cases sustained benefits after injury. Here we focus on cervical intraspinal microstimulation (ISMS) as a promising method of activating the spinal cord distal to an injury site, either to directly produce movements or more intriguingly to improve subsequent volitional control of the paretic extremities. Incomplete injuries to the spinal cord are the most commonly observed in human patients, and these injuries spare neural tissue bypassing the lesion that could be influenced by neural devices to promote recovery of function. In fact, recent results have demonstrated that therapeutic ISMS leads to modest but sustained improvements in forelimb function after an incomplete spinal cord injury (SCI). This therapeutic spinal stimulation may promote long-term recovery of function by providing the necessary electrical activity needed for neuron survival, axon growth, and synaptic stability.

Serious neck injuries in U19 rugby union players: an audit of admissions to spinal injury units in Great Britain and Ireland.

PubMed

MacLean, James G B; Hutchison, James D

2012-06-01

To obtain data regarding admissions of U19 rugby players to spinal injury units in Great Britain and Ireland and to compare this with a recent peak in presentation in Scotland. To assess the current state of data collection and subsequent analysis of serious neck injuries. To analyse the mechanism of injury in this group of at-risk players. Retrospective case series. Spinal injury units in Great Britain and Ireland. Annual frequency of serious neck injuries. Analysis of injury types, neurological deficit and mechanism of injury. 36 Injuries were recorded. 10 Of these occurred in Scotland since 1996 of which six have occurred in the past 4 years. This compared with 14 in Ireland over the same period. 12 Cases were traced in England and Wales since 2000; records were not available before this date. No prospective collation of data is performed by the home unions and inconsistency of data collection exists. The mean age was 16.2 years. 16 Of the 36 admissions had complete neurological loss, 9 had incomplete neurological injury and 11 had cervical column injury without spinal cord damage. The mechanism of injury was tackle in 17 (47%), scrum in 13 (36%), two each due to the maul and collision, and one each due to a kick and a ruck. Some degree of spinal cord injury occurred in 92% of scrum injuries (61% complete) and 53% of tackle injuries (29% complete). U19 rugby players continue to sustain serious neck injuries necessitating admission to spinal injury units with a low but persistent frequency. The recent rate of admission in Scotland is disproportionately high when the respective estimated playing populations are considered. While more injuries were sustained in the tackle, spinal cord injury was significantly more common in neck injury sustained in the scrum (p<0.001). No register of catastrophic neck injuries exists despite repeated calls over the past three decades, and a study such as this has not been reported before. Data collection of this serious category of injury is incomplete and very variable across the home unions, as a consequence a large proportion of the serious neck injuries that have occurred in U19 players over the past 14 years have not been analysed. Rigorous data collection and analysis have to be established so that problem areas of the game such as scrum engagement and the tackle can be made safer.

Spinal Plasticity and Behavior: BDNF-Induced Neuromodulation in Uninjured and Injured Spinal Cord

PubMed Central

Huie, J. Russell

2016-01-01

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic factor family of signaling molecules. Since its discovery over three decades ago, BDNF has been identified as an important regulator of neuronal development, synaptic transmission, and cellular and synaptic plasticity and has been shown to function in the formation and maintenance of certain forms of memory. Neural plasticity that underlies learning and memory in the hippocampus shares distinct characteristics with spinal cord nociceptive plasticity. Research examining the role BDNF plays in spinal nociception and pain overwhelmingly suggests that BDNF promotes pronociceptive effects. BDNF induces synaptic facilitation and engages central sensitization-like mechanisms. Also, peripheral injury-induced neuropathic pain is often accompanied with increased spinal expression of BDNF. Research has extended to examine how spinal cord injury (SCI) influences BDNF plasticity and the effects BDNF has on sensory and motor functions after SCI. Functional recovery and adaptive plasticity after SCI are typically associated with upregulation of BDNF. Although neuropathic pain is a common consequence of SCI, the relation between BDNF and pain after SCI remains elusive. This article reviews recent literature and discusses the diverse actions of BDNF. We also highlight similarities and differences in BDNF-induced nociceptive plasticity in naïve and SCI conditions. PMID:27721996

Memantine elicits spinal blockades of motor function, proprioception, and nociception in rats.

PubMed

Chen, Yu-Wen; Chiu, Chong-Chi; Liu, Kuo-Sheng; Hung, Ching-Hsia; Wang, Jhi-Joung

2015-12-01

Although memantine blocks sodium currents and produces local skin anesthesia, spinal anesthesia with memantine is unknown. The purpose of the study was to evaluate the local anesthetic effect of memantine in spinal anesthesia and its comparison with a widely used local anesthetic lidocaine. After intrathecally injecting the rats with five doses of each drug, the dose-response curves of memantine and lidocaine were constructed. The potencies of the drugs and durations of spinal anesthetic effects on motor function, proprioception, and nociception were compared with those of lidocaine. We showed that memantine produced dose-dependent spinal blockades in motor function, proprioception, and nociception. On a 50% effective dose (ED50 ) basis, the rank of potency was lidocaine greater than memantine (P < 0.05 for the differences). At the equipotent doses (ED25 , ED50 , ED75 ), the block duration produced by memantine was longer than that produced by lidocaine (P < 0.05 for the differences). Memantine, but not lidocaine, displayed more sensory/nociceptive block than motor block. The preclinical data demonstrated that memantine is less potent than lidocaine, whereas memantine produces longer duration of spinal anesthesia than lidocaine. Memantine shows a more sensory-selective action over motor blockade. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Targeted, activity-dependent spinal stimulation produces long-lasting motor recovery in chronic cervical spinal cord injury

PubMed Central

McPherson, Jacob G.; Miller, Robert R.; Perlmutter, Steve I.

2015-01-01

Use-dependent movement therapies can lead to partial recovery of motor function after neurological injury. We attempted to improve recovery by developing a neuroprosthetic intervention that enhances movement therapy by directing spike timing-dependent plasticity in spared motor pathways. Using a recurrent neural–computer interface in rats with a cervical contusion of the spinal cord, we synchronized intraspinal microstimulation below the injury with the arrival of functionally related volitional motor commands signaled by muscle activity in the impaired forelimb. Stimulation was delivered during physical retraining of a forelimb behavior and throughout the day for 3 mo. Rats receiving this targeted, activity-dependent spinal stimulation (TADSS) exhibited markedly enhanced recovery compared with animals receiving targeted but open-loop spinal stimulation and rats receiving physical retraining alone. On a forelimb reach and grasp task, TADSS animals recovered 63% of their preinjury ability, more than two times the performance level achieved by the other therapy groups. Therapeutic gains were maintained for 3 additional wk without stimulation. The results suggest that activity-dependent spinal stimulation can induce neural plasticity that improves behavioral recovery after spinal cord injury. PMID:26371306

Effect of spinal anaesthesia on the lower urinary tract in continent women.

PubMed

Haeusler, G; Sam, C; Chiari, A; Tempfer, C; Hanzal, E; Koelbl, H

1998-01-01

To evaluate the effect of spinal anaesthesia on the bladder neck position and the urethral closure function in the resting state and during clinical stress test in healthy, continent women. Controlled clinical trial. Department of Gynaecology and Obstetrics, Vienna University Medical School. Fourteen continent women, of which seven were nulliparous and seven parous, underwent minor gynaecological procedures under spinal anaesthesia. Urodynamics and ultrasound investigations were performed before and during spinal anaesthesia. Changes in the bladder neck position and the urethral closure function before and during spinal anaesthesia. Bladder neck position was found to be lower and more posterior during spinal anaesthesia as compared with pre-operative assessment. The posterior urethrovesical angle increased significantly both at rest and during maximum straining. We observed a significant increase in bladder compliance, and all parameters of the urethral pressure profile decreased significantly. While none of the nulliparous women had a positive clinical stress test during spinal anaesthesia, 4/7 parous women demonstrated leakage (Fisher's exact test, P = 0.003). Blockage of nerve supply to the pelvic floor muscles in continent women is associated with a significant loss of support of the bladder neck region confirming the theory of an active mechanism of muscular elements providing continence.

Electrical stimulation and motor recovery.

PubMed

Young, Wise

2015-01-01

In recent years, several investigators have successfully regenerated axons in animal spinal cords without locomotor recovery. One explanation is that the animals were not trained to use the regenerated connections. Intensive locomotor training improves walking recovery after spinal cord injury (SCI) in people, and >90% of people with incomplete SCI recover walking with training. Although the optimal timing, duration, intensity, and type of locomotor training are still controversial, many investigators have reported beneficial effects of training on locomotor function. The mechanisms by which training improves recovery are not clear, but an attractive theory is available. In 1949, Donald Hebb proposed a famous rule that has been paraphrased as "neurons that fire together, wire together." This rule provided a theoretical basis for a widely accepted theory that homosynaptic and heterosynaptic activity facilitate synaptic formation and consolidation. In addition, the lumbar spinal cord has a locomotor center, called the central pattern generator (CPG), which can be activated nonspecifically with electrical stimulation or neurotransmitters to produce walking. The CPG is an obvious target to reconnect after SCI. Stimulating motor cortex, spinal cord, or peripheral nerves can modulate lumbar spinal cord excitability. Motor cortex stimulation causes long-term changes in spinal reflexes and synapses, increases sprouting of the corticospinal tract, and restores skilled forelimb function in rats. Long used to treat chronic pain, motor cortex stimuli modify lumbar spinal network excitability and improve lower extremity motor scores in humans. Similarly, epidural spinal cord stimulation has long been used to treat pain and spasticity. Subthreshold epidural stimulation reduces the threshold for locomotor activity. In 2011, Harkema et al. reported lumbosacral epidural stimulation restores motor control in chronic motor complete patients. Peripheral nerve or functional electrical stimulation (FES) has long been used to activate sacral nerves to treat bladder and pelvic dysfunction and to augment motor function. In theory, FES should facilitate synaptic formation and motor recovery after regenerative therapies. Upcoming clinical trials provide unique opportunities to test the theory.

Restoration of motor function after operative reconstruction of the acutely transected spinal cord in the canine model.

PubMed

Liu, Zehan; Ren, Shuai; Fu, Kuang; Wu, Qiong; Wu, Jun; Hou, Liting; Pan, Hong; Sun, Linlin; Zhang, Jian; Wang, Bingjian; Miao, Qing; Sun, Guiyin; Bonicalzi, Vincenzo; Canavero, Sergio; Ren, Xiaoping

2018-05-01

Cephalosomatic anastomosis or what has been called a "head transplantation" requires full reconnection of the respective transected ends of the spinal cords. The GEMINI spinal cord fusion protocol has been developed for this reason. Here, we report the first randomized, controlled study of the GEMINI protocol in large animals. We conducted a randomized, controlled study of a complete transection of the spinal cord at the level of T10 in dogs at Harbin Medical University, Harbin, China. These dogs were followed for up to 8 weeks postoperatively by assessments of recovery of motor function, somato-sensory evoked potentials, and diffusion tensor imaging using magnetic resonance imaging. A total of 12 dogs were subjected to operative exposure of the dorsal aspect of the spinal cord after laminectomy and longitudinal durotomy followed by a very sharp, controlled, full-thickness, complete transection of the spinal cord at T10. The fusogen, polyethylene glycol, was applied topically to the site of the spinal cord transection in 7 of 12 dogs; 0.9% NaCl saline was applied to the site of transection in the remaining 5 control dogs. Dogs were selected randomly to receive polyethylene glycol or saline. All polyethylene glycol-treated dogs reacquired a substantial amount of motor function versus none in controls over these first 2 months as assessed on the 20-point (0-19), canine, Basso-Beattie-Bresnahan rating scale (P<.006). Somatosensory evoked potentials confirmed restoration of electrical conduction cranially across the site of spinal cord transection which improved over time. Diffusion tensor imaging, a magnetic resonance permutation that assesses the integrity of nerve fibers and cells, showed restitution of the transected spinal cord with polyethylene glycol treatment (at-injury level difference: P<.02). A sharply and fully transected spinal cord at the level of T10 can be reconstructed with restoration of many aspects of electrical continuity in large animals following the GEMINI spinal cord fusion protocol, with objective evidence of motor recovery and of electrical continuity across the site of transection, opening the way to the first cephalosomatic anastomosis. (Surgery 2017;160:XXX-XXX.). Copyright © 2017. Published by Elsevier Inc.

Axon regeneration can facilitate or suppress hindlimb function after olfactory ensheathing glia transplantation.

PubMed

Takeoka, Aya; Jindrich, Devin L; Muñoz-Quiles, Cintia; Zhong, Hui; van den Brand, Rubia; Pham, Daniel L; Ziegler, Matthias D; Ramón-Cueto, Almudena; Roy, Roland R; Edgerton, V Reggie; Phelps, Patricia E

2011-03-16

Reports based primarily on anatomical evidence suggest that olfactory ensheathing glia (OEG) transplantation promotes axon regeneration across a complete spinal cord transection in adult rats. Based on functional, electrophysiological, and anatomical assessments, we found that OEG promoted axon regeneration across a complete spinal cord transection and that this regeneration altered motor responses over time. At 7 months after transection, 70% of OEG-treated rats showed motor-evoked potentials in hindlimb muscles after transcranial electric stimulation. Furthermore, a complete spinal cord retransection performed 8 months after injury demonstrated that this axon regeneration suppressed locomotor performance and decreased the hypersensitive hindlimb withdrawal response to mechanical stimulation. OEG transplantation alone promoted reorganization of lumbosacral locomotor networks and, when combined with long-term training, enhanced some stepping measures. These novel findings demonstrate that OEG promote regeneration of mature axons across a complete transection and reorganization of spinal circuitry, both of which contribute to sensorimotor function.

How to make spinal motor neurons.

PubMed

Davis-Dusenbery, Brandi N; Williams, Luis A; Klim, Joseph R; Eggan, Kevin

2014-02-01

All muscle movements, including breathing, walking, and fine motor skills rely on the function of the spinal motor neuron to transmit signals from the brain to individual muscle groups. Loss of spinal motor neuron function underlies several neurological disorders for which treatment has been hampered by the inability to obtain sufficient quantities of primary motor neurons to perform mechanistic studies or drug screens. Progress towards overcoming this challenge has been achieved through the synthesis of developmental biology paradigms and advances in stem cell and reprogramming technology, which allow the production of motor neurons in vitro. In this Primer, we discuss how the logic of spinal motor neuron development has been applied to allow generation of motor neurons either from pluripotent stem cells by directed differentiation and transcriptional programming, or from somatic cells by direct lineage conversion. Finally, we discuss methods to evaluate the molecular and functional properties of motor neurons generated through each of these techniques.

Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury.

PubMed

Keirstead, Hans S; Nistor, Gabriel; Bernal, Giovanna; Totoiu, Minodora; Cloutier, Frank; Sharp, Kelly; Steward, Oswald

2005-05-11

Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin-forming cells. Here, we show that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.

Axon Regeneration Can Facilitate or Suppress Hindlimb Function after Olfactory Ensheathing Glia Transplantation

PubMed Central

Takeoka, Aya; Jindrich, Devin L.; Muñoz-Quiles, Cintia; Zhong, Hui; van den Brand, Rubia; Pham, Daniel L.; Ziegler, Matthias D.; Ramón-Cueto, Almudena; Roy, Roland R.; Edgerton, V. Reggie

2011-01-01

Reports based primarily on anatomical evidence suggest that olfactory ensheathing glia (OEG) transplantation promotes axon regeneration across a complete spinal cord transection in adult rats. Based on functional, electrophysiological, and anatomical assessments, we found that OEG promoted axon regeneration across a complete spinal cord transection and that this regeneration altered motor responses over time. At 7 months after transection, 70% of OEG-treated rats showed motor-evoked potentials in hindlimb muscles after transcranial electric stimulation. Furthermore, a complete spinal cord retransection performed 8 months after injury demonstrated that this axon regeneration suppressed locomotor performance and decreased the hypersensitive hindlimb withdrawal response to mechanical stimulation. OEG transplantation alone promoted reorganization of lumbosacral locomotor networks and, when combined with long-term training, enhanced some stepping measures. These novel findings demonstrate that OEG promote regeneration of mature axons across a complete transection and reorganization of spinal circuitry, both of which contribute to sensorimotor function. PMID:21411671

Anterior spinal artery syndrome. Paraplegia following segmental ischaemic injury to the spinal cord after oesophagectomy.

PubMed

Djurberg, H; Haddad, M

1995-04-01

A case of unexpected paraplegia after oesophageal resection under general anaesthesia combined with epidural analgesia and intra-operative intercostal block is described. Patients with compromised cardiovascular and respiratory function undergoing thoracic or major abdominal surgery can benefit significantly intra-operatively from a combination of general anaesthesia and regional analgesia. The continued use of regional analgesia into the postoperative period offers even more advantages. General anaesthesia administered before regional analgesia may, however, mask complications related to the regional technique and delay the instigation of corrective measures. The blood supply to the anterior part of the spinal cord, through the artery of Adamkiewicz, may be impaired intra-operatively leading to neurological sequelae known as the anterior spinal artery syndrome, characterised by loss of motor function with intact or partially intact sensory function. Patients at risk of developing the syndrome can be identified pre-operatively.

Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy

PubMed Central

Mentis, George Z.; Blivis, Dvir; Liu, Wenfang; Drobac, Estelle; Crowder, Melissa E.; Kong, Lingling; Alvarez, Francisco J.; Sumner, Charlotte J.; O'Donovan, Michael J.

2011-01-01

SUMMARY To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes illustrating the reversibility of these synaptic defects. De-afferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention. PMID:21315257

Emerging treatment options for spinal muscular atrophy.

PubMed

Burnett, Barrington G; Crawford, Thomas O; Sumner, Charlotte J

2009-03-01

The motor neuron disease spinal muscular atrophy (SMA) is one of the leading genetic killers of infants worldwide. SMA is caused by mutation of the survival motor neuron 1 (SMN1) gene and deficiency of the survival motor neuron (SMN) protein. All patients retain one or more copies of the SMN2 gene, which (by producing a small amount of the SMN protein) rescues embryonic lethality and modifies disease severity. Rapid progress continues in dissecting the cellular functions of the SMN protein, but the mechanisms linking SMN deficiency with dysfunction and loss of functioning motor units remain poorly defined. Clinically, SMA should to be distinguished from other neuromuscular disorders, and the diagnosis can be readily confirmed with genetic testing. Quality of life and survival of SMA patients are improved with aggressive supportive care including optimized respiratory and nutritional care and management of scoliosis and contractures. Because SMA is caused by inadequate amounts of SMN protein, one aim of current SMA therapeutics development is to increase SMN protein levels in SMA patients by activating SMN2 gene expression and/or increasing levels of full-length SMN2 transcripts. Several potential therapeutic compounds are currently being studied in clinical trials in SMA patients.

A PET/CT approach to spinal cord metabolism in amyotrophic lateral sclerosis.

PubMed

Marini, Cecilia; Cistaro, Angelina; Campi, Cristina; Calvo, Andrea; Caponnetto, Claudia; Nobili, Flavio Mariano; Fania, Piercarlo; Beltrametti, Mauro C; Moglia, Cristina; Novi, Giovanni; Buschiazzo, Ambra; Perasso, Annalisa; Canosa, Antonio; Scialò, Carlo; Pomposelli, Elena; Massone, Anna Maria; Bagnara, Maria Caludia; Cammarosano, Stefania; Bruzzi, Paolo; Morbelli, Silvia; Sambuceti, Gianmario; Mancardi, Gianluigi; Piana, Michele; Chiò, Adriano

2016-10-01

In amyotrophic lateral sclerosis, functional alterations within the brain have been intensively assessed, while progression of lower motor neuron damage has scarcely been defined. The aim of the present study was to develop a computational method to systematically evaluate spinal cord metabolism as a tool to monitor disease mechanisms. A new computational three-dimensional method to extract the spinal cord from (18)F-FDG PET/CT images was evaluated in 30 patients with spinal onset amyotrophic lateral sclerosis and 30 controls. The algorithm identified the skeleton on the CT images by using an extension of the Hough transform and then extracted the spinal canal and the spinal cord. In these regions, (18)F-FDG standardized uptake values were measured to estimate the metabolic activity of the spinal canal and cord. Measurements were performed in the cervical and dorsal spine and normalized to the corresponding value in the liver. Uptake of (18)F-FDG in the spinal cord was significantly higher in patients than in controls (p < 0.05). By contrast, no significant differences were observed in spinal cord and spinal canal volumes between the two groups. (18)F-FDG uptake was completely independent of age, gender, degree of functional impairment, disease duration and riluzole treatment. Kaplan-Meier analysis showed a higher mortality rate in patients with standardized uptake values above the fifth decile at the 3-year follow-up evaluation (log-rank test, p < 0.01). The independence of this value was confirmed by multivariate Cox analysis. Our computational three-dimensional method enabled the evaluation of spinal cord metabolism and volume and might represent a potential new window onto the pathophysiology of amyotrophic lateral sclerosis.

Rapid activity-dependent modulation of the intrinsic excitability through up-regulation of KCNQ/Kv7 channel function in neonatal spinal motoneurons.

PubMed

Lombardo, Joseph; Sun, Jianli; Harrington, Melissa A

2018-01-01

Activity-dependent changes in the properties of the motor system underlie the necessary adjustments in its responsiveness on the basis of the environmental and developmental demands of the organism. Although plastic changes in the properties of the spinal cord have historically been neglected because of the archaic belief that the spinal cord is constituted by a hardwired network that simply relays information to muscles, plenty of evidence has been accumulated showing that synapses impinging on spinal motoneurons undergo short- and long-term plasticity. In the brain, brief changes in the activity level of the network have been shown to be paralleled by changes in the intrinsic excitability of the neurons and are suggested to either reinforce or stabilize the changes at the synaptic level. However, rapid activity-dependent changes in the intrinsic properties of spinal motoneurons have never been reported. In this study, we show that in neonatal mice the intrinsic excitability of spinal motoneurons is depressed after relatively brief but sustained changes in the spinal cord network activity. Using electrophysiological techniques together with specific pharmacological blockers of KCNQ/Kv7 channels, we demonstrate their involvement in the reduction of the intrinsic excitability of spinal motoneurons. This action results from an increased M-current, the product of the activation of KCNQ/Kv7 channels, which leads to a hyperpolarization of the resting membrane potential and a decrease in the input resistance of spinal motoneurons. Computer simulations showed that specific up-regulations in KCNQ/Kv7 channels functions lead to a modulation of the intrinsic excitability of spinal motoneurons as observed experimentally. These results indicate that KCNQ/Kv7 channels play a fundamental role in the activity-dependent modulation of the excitability of spinal motoneurons.

Rehabilitation outcomes after infection-related spinal cord disease: a retrospective analysis.

PubMed

McKinley, William; Merrell, Christopher; Meade, Michelle; Brooke, Karen; DiNicola, Anthony

2008-04-01

To compare injury characteristics, demographics, and functional outcomes of patients with infection-related spinal cord disease (IR-SCD) vs. those with traumatic spinal cord injury (SCI). A 10-yr retrospective review of 34 consecutive patients with IR-SCD admitted to an SCI rehabilitation unit at a Level 1 tertiary university medical center. Outcome measures included length of stay (LOS), FIM motor scores, and home discharge rates. The cause of IR-SCD was most often spinal epidural abscess secondary to Staphylococcus aureus (74%). Weakness (90%) and neck/back pain (84%) were the most frequent initial admitting symptoms. Identifiable risk factors included history of recent infection (42%), diabetes mellitus (32%), and intravenous drug abuse (26%). SCD-related complications most commonly included pain (81%), urinary tract infection (52%), and spasticity (45%). When compared with traumatic SCI (n = 560), patients with IR-SCD comprised significantly less of the SCI/D rehabilitation admissions (3% vs. 61%), were older (53 vs. 40 yrs), and more often female (35% vs. 16%). Injuries were more commonly located in the thoracic region (48% vs. 38%). Patients with IR-SCD more often had incomplete injuries (94% vs. 57%). Thirty-two percent of IR-SCD patients had improvements in AIS impairment scale classification. LOS was longer on acute care (25 vs. 16 days), but similar on rehabilitation (36 vs. 34 days), and with lower FIM motor changes (16.2 vs. 22.8) during rehabilitation. Patients with IR-SCD were less often discharged to home (56% vs. 75%). Patients with infection-related SCD comprise a significant subset of SCI/D rehabilitation admissions and have differing demographic and injury characteristics compared with traumatic SCI. Despite less-severe injury characteristics and similar rehabilitation LOS, they achieve lower functional improvements and are less often discharged home, underscoring the importance of patient/family education and discharge planning.

Effects of core body temperature on changes in spinal somatosensory-evoked potential in acute spinal cord compression injury: an experimental study in the rat.

PubMed

Jou, I M

2000-08-01

Acute spinal cord injury was induced by a clip compression model in rats to approximate spinal cord injury encountered in spinal surgery. Spinal somatosensory-evoked potential neuromonitoring was used to study the electrophysiologic change. To compare and correlate changes in evoked potential after acute compression at different core temperatures with postoperative neurologic function and histologic change, to evaluate current intraoperative neuromonitoring warning criteria for neural damage, and to confirm the protective effect of hypothermia in acute spinal cord compression injury by electrophysiologic, histologic, and clinical observation. With the increase in aggressive correction of spinal deformities, and the invasiveness of surgical instruments, the incidence of neurologic complication appears to have increased despite the availability of sensitive intraoperative neuromonitoring techniques designed to alert surgeons to impending neural damage. Many reasons have been given for the frequent failures of neuromonitoring, but the influence of temperature-a very important and frequently encountered factor-on evoked potential has not been well documented. Specifically, decrease in amplitude and elongation of latency seem not to have been sufficiently taken into account when intraoperative neuromonitoring levels were interpreted and when acceptable intraoperative warning criteria were determined. Experimental acute spinal cord injury was induced in rats by clip compression for two different intervals and at three different core temperatures. Spinal somatosensory-evoked potential, elicited by stimulating the median nerve and recorded from the cervical interspinous C2-C3, was monitored immediately before and after compression, and at 15-minute intervals for 1 hour. Spinal somatosensory-evoked potential change is almost parallel to temperature-based amplitude reduction and latency elongation. Significant neurologic damage induced by acute compression of the cervical spinal cord produced a degree of effect on the amplitude of spinal somatosensory-evoked potential in normothermic conditions that differed from the effect in moderately hypothermic conditions. Using the same electromonitoring criteria,moderately hypothermic groups showed a significantly higher false-negative rate statistically (35%) than normothermic groups (10%). Systemic cooling may protect against the detrimental effects of aggressive spinal surgical procedures. There is still not enough published information available to establish statistically and ethically acceptable intraoperative neuromonitoring warning and intervention criteria conclusively. Therefore, an urgent need exists for further investigation. Although a reduction of more than 50% in evoked potential still seems acceptable as an indicator of impending neural function loss, maintenance of more than 50% of baseline evoked potential is no guarantee of normal postoperative neural function, especially at lower than normal temperatures.

Spinal instrumentation for Duchenne's muscular dystrophy: experience of hypotensive anaesthesia to minimise blood loss.

PubMed

Fox, H J; Thomas, C H; Thompson, A G

1997-01-01

Nineteen patients with Duchenne's muscular dystrophy underwent segmental spinal instrumentation and posterior fusion between 1989 and 1994. The indication for surgery was loss of the ability to walk and development of scoliosis with sitting discomfort. Preoperative assessment included evaluation of pulmonary function. Average age at operation was 12.5 years. Instrumentation and fusion extended from upper thoracic levels to L-5 or the sacrum. A Hartshill rectangle was used in all cases, with banked allograft bone. Severe intraoperative blood loss was avoided by use of hypotensive anaesthesia. Peroperatively, systolic blood pressure was maintained between 75 and 85 mm Hg. Average blood loss was 1,246 ml (range, 400-3,100) or 30% of estimated total blood volume. Average transfusion requirements were 3 units of packed cells. Postoperative analgesia was provided by infusion via an epidural catheter. There were no postoperative wound or chest infections. Three patients required catheterisation for urinary retention. Postoperatively patients were fitted with a Neofract jacket to allow early mobilisation and discharge. Mean postoperative length of stay was 16 days. Posterior spinal fusion by using the Hartshill rectangle provided good correction and fixation. Hypotensive anaesthesia permitted surgery to be performed rapidly in a relatively dry field and avoided the complications of severe intraoperative blood loss and massive transfusion.

An overview of the regulatory aspects of medical devices from the viewpoint of research and device manufacturing.

PubMed

Patrick, J

1993-01-01

To review the Food and Drug Administration's regulatory requirements for bringing a new or substantially changed medical device to market in the United States, noting the history and current requirements for the continuous spinal catheter. The relevant laws and guidelines for classifying, testing, and submitting a device to Food and Drug Administration approval are reviewed. The Food and Drug Administration categorizes medical devices into three classes, based on potential risk for illness or injury presented by a malfunction or failure. Class III devices are the most critical ones, and require a Premarket Approval that includes clinical trials before market introduction. Classes I and II usually require a 510(k), or premarket notification, which usually does not need any clinical data. Testing requirements include biocompatibility testing; physical, functional, and packaging testing; and sterility testing. The continuous spinal catheter (25-32 gauge) was marketed under a 510(k) claiming substantial equivalence to the Bizzarri-Giuffrida 24-gauge catheter, which was a pre-Amendment device. After incidences of cauda equina syndrome were reported with use of the continuous spinal technique, the Food and Drug Administration reclassified the small-gauge catheters as Class III devices, which require a Premarket Approval before being marketed.

Effectiveness of Activity-Based Therapy in Comparison with Surface Spinal Stimulation in People with Traumatic Incomplete Spinal Cord Injury for Activation of Central Pattern Generator for Locomotion: Study Protocol for a 24-Week Randomized Controlled Trial.

PubMed

Bedi, Parneet Kaur; Arumugam, Narkeesh; Chhabra, Harvinder Singh

2018-06-01

A multi-centric randomized controlled trial to be conducted at two sites, department of phyhysiotherapypy, Punjabi University, Patiala and rehabilitation department, Indian Spinal Injury Centre, New Delhi, India. To determine the effectiveness of activity-based therapy in comparison with surface spinal stimulation (SSS) in traumatic incomplete spinal cord injury (SCI) with special reference to locomotion-a central pattern generator controlled function. A major goal for many patients after SCI is to regain the function of locomotion. It is crucial that rehabilitation strives to maximize locomotor ability and functional recovery after SCI. Experimental evidence of improvement in stepping and motor control after activity-based training in animal models and human SCI has been translated into clinical neuro-rehabilitation. Control group participants will undertake an intensive 24-week duration thrice weekly program of activity-based therapy. In addition to this the participants in experimental group will also receive a session of 45 minutes of SSS on thrice weekly basis. The primary analysis for our study will be at 24 weeks. Linear regression will be used to determine the mean between-group differences and 95% confidence interval for all continuous outcomes using baseline scores and group allocation as covariates. The primary outcome measure is improvement in the level of walking index for SCI-II. The secondary outcome measures are modified Ashworth scale, Penn spasm frequency score, spinal cord independence measure-III, SCI functional ambulation inventory, Hoffman's reflex, somatosensory evoked potential, and American Spinal Injury Association Impairment Scale scores. An insight into training-induced mechanisms will be of great importance to fine tune such combined treatments and vindicate their efficacy in restoration of locomotion and functional activities in individuals with SCI.

The impact of pain on spiritual well-being in people with a spinal cord injury.

PubMed

Siddall, P J; McIndoe, L; Austin, P; Wrigley, P J

2017-01-01

The study uses a cross-sectional, group comparison, questionnaire-based design. To determine whether spinal cord injury and pain have an impact on spiritual well-being and whether there is an association between spiritual well-being and measures of pain and psychological function. University teaching hospital in Sydney, New South Wales, Australia. Questionnaires evaluating pain, psychological and spiritual well-being were administered to a group of people with a spinal cord injury (n=53) and a group without spinal cord injury (n=37). Spiritual well-being was assessed using the Functional Assessment of Chronic Illness and Therapy - Spirituality Extended Scale (FACIT-Sp-Ex). Pain and psychological function were also assessed using standard, validated measures of pain intensity, pain interference, mood and cognition. Levels of spiritual well-being in people with a spinal cord injury were significantly lower when compared with people without a spinal cord injury. In addition, there was a moderate but significant negative correlation between spiritual well-being and pain intensity. There was also a strong and significant negative correlation between depression and spiritual well-being and a strong and significant positive correlation between spiritual well-being and both pain self-efficacy and satisfaction with life. Consequences of a spinal cord injury include increased levels of spiritual distress, which is associated, with higher levels of pain and depression and lower levels of pain self-efficacy and satisfaction with life. These findings indicate the importance of addressing spiritual well-being as an important component in the long-term rehabilitation of any person following spinal cord injury. This study was supported by grant funding from the Australian and New Zealand College of Anaesthetists, and the National Health and Medical Research Council of Australia.

Effects of polarization in low-level laser therapy of spinal cord injury in rats

NASA Astrophysics Data System (ADS)

Ando, Takahiro; Sato, Shunichi; Kobayashi, Hiroaki; Nawashiro, Hiroshi; Ashida, Hiroshi; Hamblin, Michael R.; Obara, Minoru

2012-03-01

Low-level laser therapy (LLLT) is a promising approach to treat the spinal cord injury (SCI). Since nerve fibers have optical anisotropy, propagation of light in the spinal tissue might be affected by its polarization direction. However, the effect of polarization on the efficacy of LLLT has not been elucidated. In the present study, we investigated the effect of polarization on the efficacy of near-infrared LLLT for SCI. Rat spinal cord was injured with a weight-drop device. The lesion site was irradiated with an 808-nm diode laser beam that was transmitted through a polarizing filter immediately after injury and daily for five consecutive days. The laser power at the injured spinal cord surface was 25 mW, and the dosage per day was 9.6 J/cm2 (spot diameter, 2 cm; irradiation duration, 1200 s). Functional recovery was assessed daily by an open-field test. The results showed that the functional scores of the SCI rats that were treated with 808-nm laser irradiation were significantly higher than those of the SCI alone group (Group 1) from day 5 after injury, regardless of the polarization direction. Importantly, as compared to the locomotive function of the SCI rats that were treated with the perpendicularly-polarized laser parallel to the spinal column (Group 2), that of the SCI rats that were irradiated with the linearly aligned polarization (Group 3) was significantly improved from day 10 after injury. In addition, the ATP contents in the injured spinal tissue of Group 3, which were measured immediately after laser irradiation, were moderately higher than those of Group 2. These observations are attributable to the deeper penetration of the parallelpolarized light in the anisotropic spinal tissue, suggesting that polarization direction significantly affects the efficacy of LLLT for SCI.

Osthole attenuates spinal cord ischemia-reperfusion injury through mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction in rats.

PubMed

Zhou, Yue-fei; Li, Liang; Feng, Feng; Yuan, Hua; Gao, Da-kuan; Fu, Luo-an; Fei, Zhou

2013-12-01

Osthole, the main bioactive compounds isolated from the traditional Chinese medical herb broad Cnidium monnieri (L.) cusson, has been shown to exert spectrum of pharmacologic activities. The aim of this study was to investigate the potential neuroprotective effects of osthole against spinal cord ischemia-reperfusion injury in rats. Osthole was administrated at the concentration of 0.1, 1, 10, 50, or 200 mg/kg (intraperitoneally) 1 h before spinal cord ischemia. The effects on spinal cord injury were measured by spinal cord water content, infarct volume, hematoxylin and eosin staining, and neurologic assessment. Mitochondria were purified from injured spinal cord tissue to determine mitochondrial function. We found that treatment with osthole (10 and 50 mg/kg) significantly decreased spinal cord water content and infarct volume, preserved normal motor neurons, and improved neurologic functions. These protective effects can be also observed even if the treatment was delayed to 4 h after reperfusion. Osthole treatment preserved mitochondrial membrane potential level, reduced reactive oxygen species production, increased adenosine triphosphate generation, and inhibited cytochrome c release in mitochondrial samples. Moreover, osthole increased mitochondria respiratory chain complex activities in spinal cord tissue, with no effect on mitochondrial DNA content and the expression of mitochondrial-specific transcription factors. All these findings demonstrate the neuroprotective effect of osthole in spinal cord ischemia-reperfusion injury model and suggest that oshtole-induced neuroprotection was mediated by mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

Shock Wave Treatment Protects From Neuronal Degeneration via a Toll-Like Receptor 3 Dependent Mechanism: Implications of a First-Ever Causal Treatment for Ischemic Spinal Cord Injury.

PubMed

Lobenwein, Daniela; Tepeköylü, Can; Kozaryn, Radoslaw; Pechriggl, Elisabeth J; Bitsche, Mario; Graber, Michael; Fritsch, Helga; Semsroth, Severin; Stefanova, Nadia; Paulus, Patrick; Czerny, Martin; Grimm, Michael; Holfeld, Johannes

2015-10-27

Paraplegia following spinal cord ischemia represents a devastating complication of both aortic surgery and endovascular aortic repair. Shock wave treatment was shown to induce angiogenesis and regeneration in ischemic tissue by modulation of early inflammatory response via Toll-like receptor (TLR) 3 signaling. In preclinical and clinical studies, shock wave treatment had a favorable effect on ischemic myocardium. We hypothesized that shock wave treatment also may have a beneficial effect on spinal cord ischemia. A spinal cord ischemia model in mice and spinal slice cultures ex vivo were performed. Treatment groups received immediate shock wave therapy, which resulted in decreased neuronal degeneration and improved motor function. In spinal slice cultures, the activation of TLR3 could be observed. Shock wave effects were abolished in spinal slice cultures from TLR3(-/-) mice, whereas the effect was still present in TLR4(-/-) mice. TLR4 protein was found to be downregulated parallel to TLR3 signaling. Shock wave-treated animals showed significantly better functional outcome and survival. The protective effect on neurons could be reproduced in human spinal slices. Shock wave treatment protects from neuronal degeneration via TLR3 signaling and subsequent TLR4 downregulation. Consequently, it represents a promising treatment option for the devastating complication of spinal cord ischemia after aortic repair. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Duration of motor block with intrathecal ropivacaine versus bupivacaine for caesarean section: a meta-analysis.

PubMed

Malhotra, R; Johnstone, C; Halpern, S; Hunter, J; Banerjee, A

2016-08-01

Bupivacaine is a commonly used local anaesthetic for spinal anaesthesia for caesarean section, but may produce prolonged motor block, delaying discharge from the post-anaesthesia care unit. Ropivacaine may have a shorter time to recovery of motor function compared with bupivacaine. We performed a meta-analysis to assess the time difference in duration of motor block with intrathecal ropivacaine compared with bupivacaine for caesarean section. We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases for randomised controlled trials comparing ropivacaine with bupivacaine in parturients undergoing elective caesarean section under spinal anaesthesia. The primary outcome was the duration of motor block. Secondary outcomes included the time to onset of sensory block, need for conversion to general anaesthesia and the incidence of hypotension. Thirteen trials comprising 743 spinal anaesthetics were included. Intrathecal ropivacaine resulted in a reduced duration of motor block, regressing 35.7min earlier compared with intrathecal bupivacaine (P<0.00001). There was no difference in the time to onset of sensory block (P=0.25) or the incidence of hypotension (P=0.10). Limited data suggested no difference in the rate of conversion to general anaesthesia, but an earlier request for postoperative analgesia with ropivacaine. Compared with bupivacaine, intrathecal ropivacaine is associated with more rapid recovery of motor block despite similar sensory properties and no increased rate of conversion to general anaesthesia. This may be useful in centres in which recovery of motor block is a criterion for discharge from the post-anaesthesia care unit. However, small numbers of trials and significant heterogeneity limit the interpretation of our results. Copyright © 2016 Elsevier Ltd. All rights reserved.

Charles Edouard Brown-Séquard's departure from the Medical College of Virginia: incompatible science or incompatible social views in pre-Civil War southern United States.

PubMed

Watson, Joseph C; Ho, Stephen V

2011-01-01

Charles Edouard Brown-Séquard was one of the most colorful characters in modern physiology. His scientific methods of self-experimentation and animal vivisection led to many great observations, including the eponymous syndrome of hemisection of the spinal cord. Despite his renown, he stayed but one year in his first major academic post. Details of his sojourn at the Medical College of Virginia (now part of Virginia Commonwealth University) in Richmond were divined from perusal of archival material, letters, and from the available literature. His notoriety in the field of physiology landed him a post at the Medical College of Virginia in 1854 as the chair of physiology. During a brief time here, he was able to publish his landmark monograph of 1855 on the pathways of the spinal cord "Experimental and Clinical Researches on the Physiology and Pathology of the Spinal Cord." He had a near-death experience while experimenting on himself to determine the function of the skin. It was rumored that his English was poor, his lectures unintelligible, and his scientific methods disturbing to the neighbors and that for those reasons he was asked to vacate his post. Personal communications and other accounts indicate a different view: his mixed-blood heritage and his views on slavery were unpopular in the pre-Civil War southern United States. These disparate viewpoints lend an insight into the life and career of this pioneer in modern medicine and experimental design and to the clash of science and social views. Copyright © 2011 Elsevier Inc. All rights reserved.

Quantification of the proportion of motor neurons recruited by transcranial electrical stimulation during intraoperative motor evoked potential monitoring.

PubMed

Tsutsui, Shunji; Yamada, Hiroshi; Hashizume, Hiroshi; Minamide, Akihito; Nakagawa, Yukihiro; Iwasaki, Hiroshi; Yoshida, Munehito

2013-12-01

Transcranial motor evoked potentials (TcMEPs) are widely used to monitor motor function during spinal surgery. However, they are much smaller and more variable in amplitude than responses evoked by maximal peripheral nerve stimulation, suggesting that a limited number of spinal motor neurons to the target muscle are excited by transcranial stimulation. The aim of this study was to quantify the proportion of motor neurons recruited during TcMEP monitoring under general anesthesia. In twenty patients who underwent thoracic and/or lumbar spinal surgery with TcMEP monitoring, the triple stimulation technique (TST) was applied to the unilateral upper arm intraoperatively. Total intravenous anesthesia was employed. Trains of four stimuli were delivered with maximal intensity and an inter-pulse interval of 1.5 ms. TST responses were recorded from the abductor digiti minimi muscle, and the negative peak amplitude and area were measured and compared between the TST test (two collisions between transcranial and proximal and distal peripheral stimulation) and control response (two collisions between two proximal and one distal peripheral stimulation). The highest degree of superimposition of the TST test and control responses was chosen from several trials per patient. The average ratios (test:control) were 17.1 % (range 1.8-38 %) for the amplitudes and 21.6 % (range 2.9-40 %) for the areas. The activity of approximately 80 % of the motor units to the target muscle cannot be detected by TcMEP monitoring. Therefore, changes in evoked potentials must be interpreted cautiously when assessing segmental motor function with TcMEP monitoring.

Somatropin treatment of spinal muscular atrophy: a placebo-controlled, double-blind crossover pilot study.

PubMed

Kirschner, J; Schorling, D; Hauschke, D; Rensing-Zimmermann, C; Wein, U; Grieben, U; Schottmann, G; Schara, U; Konrad, K; Müller-Felber, W; Thiele, S; Wilichowski, E; Hobbiebrunken, E; Stettner, G M; Korinthenberg, R

2014-02-01

In preclinical studies growth hormone and its primary mediator IGF-1 have shown potential to increase muscle mass and strength. A single patient with spinal muscular atrophy reported benefit after compassionate use of growth hormone. Therefore we evaluated the efficacy and safety of growth hormone treatment for spinal muscular atrophy in a multicenter, randomised, double-blind, placebo-controlled, crossover pilot trial. Patients (n = 19) with type II/III spinal muscular atrophy were randomised to receive either somatropin (0.03 mg/kg/day) or placebo subcutaneously for 3 months, followed by a 2-month wash-out phase before 3 months of treatment with the contrary remedy. Changes in upper limb muscle strength (megascore for elbow flexion and hand-grip in Newton) were assessed by hand-held myometry as the primary measure of outcome. Secondary outcome measures included lower limb muscle strength, motor function using the Hammersmith Functional Motor Scale and other functional tests for motor function and pulmonary function. Somatropin treatment did not significantly affect upper limb muscle strength (point estimate mean: 0.08 N, 95% confidence interval (CI:-3.79;3.95, p = 0.965), lower limb muscle strength (point estimate mean: 2.23 N, CI:-2.19;6.63, p = 0.302) or muscle and pulmonary function. Side effects occurring during somatropin treatment corresponded with well-known side effects of growth hormone substitution in patients with growth hormone deficiency. In this pilot study, growth hormone treatment did not improve muscle strength or function in patients with spinal muscular atrophy type II/III. Copyright © 2013 Elsevier B.V. All rights reserved.

Behavioral and anatomical consequences of repetitive mild thoracic spinal cord contusion injury in the rat.

PubMed

Jin, Ying; Bouyer, Julien; Haas, Christopher; Fischer, Itzhak

2014-07-01

Moderate and severe spinal cord contusion injuries have been extensively studied, yet much less is known about mild injuries. Mild contusions result in transient functional deficits, proceeding to near-complete recovery, but they may render the spinal cord vulnerable to future injuries. However, to date there have been no appropriate models to study the behavioral consequences, anatomical changes, and susceptibility of a mild contusion to repeated injuries, which may occur in children as well as adults during competitive sport activities. We have developed a novel mild spinal cord contusion injury model characterized by a sequence of transient functional deficits after the first injury and restoration to near-complete motor and sensory function, which is then followed up by a second injury. This model can serve not only to study the effects of repeated injuries on behavioral and anatomical changes, but also to examine the relationship between successive tissue damage and recovery of function. In the present study, we confirmed that mild thoracic spinal cord contusion, utilizing the NYU impactor device, resulted in localized tissue damage, characterized by a cystic cavity and peripheral rim of spared white matter at the injury epicenter, and rapid functional recovery to near-normal levels utilizing several behavioral tests. Repeated injury after 3weeks, when functional recovery has been completed, resulted in worsening of both motor and sensory function, which did not recover to prior levels. Anatomical analyses showed no differences in the volumes of spared white matter, lesion, or cyst, but revealed modest extension of lesion area rostral to the injury epicenter as well as an increase in inflammation and apoptosis. These studies demonstrate that a mild injury model can be used to test efficacy of treatments for repeated injuries and may serve to assist in the formulation of policies and clinical practice regarding mild SCI injury and spinal concussion. Copyright © 2014 Elsevier Inc. All rights reserved.

Neuroprotective effect of curcumin on spinal cord in rabbit model with ischemia/reperfusion.

PubMed

Liu, Zhi-Qiang; Xing, Shan-Shan; Zhang, Wei

2013-03-01

Ischemic/reperfusion (I/R) injury of the spinal cord is a serious complication that can result from thoracoabdominal aortic surgery. To investigate the neuroprotective effect of curcumin against I/R injury in a rabbit model. A total of 36 rabbits were randomly divided into three groups: sham, I/R, and curcumin-treated group. Rabbits were subject to 30-min aortic occlusion to induce transient spinal cord ischemia. Neurological function was observed after reperfusion and spinal cord segment (L3-L5) was collected for histopathological evaluation. Malondialdehyde (MDA) and total superoxide dismutase (SOD) activity were also assayed. Rabbits in I/R group were induced to paraplegia. While after 48-hour treatment, compared with I/R group, curcumin significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05). The results suggest that curcumin, at least in an animal model, can attenuate transient spinal cord ischemic injury potentially via reducing oxidative damage, which may provide a novel approach in the treatment of spinal cord ischemic injury.

Finite element analysis and cadaveric cinematic analysis of fixation options for anteriorly implanted trabecular metal interbody cages.

PubMed

Berjano, Pedro; Blanco, Juan Francisco; Rendon, Diego; Villafañe, Jorge Hugo; Pescador, David; Atienza, Carlos Manuel

2015-11-01

To assess, with finite element analysis and an in vitro biomechanical study in cadaver, whether the implementation of an anterior interbody cage made of hedrocel with nitinol shape memory staples in compression increases the stiffness of the stand-alone interbody cage and to compare these constructs' stiffness to other constructs common in clinical practice. A biomechanical study with a finite element analysis and cadaveric testing assessed the stiffness of different fixation modes for the L4-L5 functional spinal unit: intact spine, destabilized spine with discectomy, posterior pedicle-screw fixation, anterior stand-alone interbody cage, anterior interbody cage with bilateral pedicle screws and anterior interbody cage with two shape memory staples in compression. These modalities of vertebral fixation were compared in four loading modes (flexion, extension, lateral bending, and axial rotation). The L4-L5 spinal unit with an anterior interbody cage and two staples was stiffer than the stand-alone cage. The construct stiffness was similar to that of a model of posterior pedicular stabilization. The stiffness was lower than that of the anterior cage plus bilateral pedicle-screw fixation. The use of an anterior interbody implant with shape memory staples in compression may be an alternative to isolated posterior fixation and to anterior isolated implants, with increased stiffness.

Learning from the spinal cord: How the study of spinal cord plasticity informs our view of learning

PubMed Central

Grau, James W.

2013-01-01

The paper reviews research examining whether and how training can induce a lasting change in spinal cord function. A framework for the study of learning, and some essential issues in experimental design, are discussed. A core element involves delayed assessment under common conditions. Research has shown that brain systems can induce a lasting (memory-like) alteration in spinal function. Neurons within the lower (lumbosacral) spinal cord can also adapt when isolated from the brain by means of a thoracic transection. Using traditional learning paradigms, evidence suggests that spinal neurons support habituation and sensitization as well as Pavlovian and instrumental conditioning. At a neurobiological level, spinal systems support phenomena (e.g., long-term potentiation), and involve mechanisms (e.g., NMDA mediated plasticity, protein synthesis) implicated in brain-dependent learning and memory. Spinal learning also induces modulatory effects that alter the capacity for learning. Uncontrollable/unpredictable stimulation disables the capacity for instrumental learning and this effect has been linked to the cytokine tumor necrosis factor (TNF). Predictable/controllable stimulation enables learning and counters the adverse effects of uncontrollable simulation through a process that depends upon brain-derived neurotrophic factor (BDNF). Finally, uncontrollable, but not controllable, nociceptive stimulation impairs recovery after a contusion injury. A process-oriented approach (neurofunctionalism) is outlined that encourages a broader view of learning phenomena. PMID:23973905

Comparing patients with spinal cord infarction and cerebral infarction: clinical characteristics, and short-term outcome.

PubMed

Naess, Halvor; Romi, Fredrik

2011-01-01

To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis.

Comparing patients with spinal cord infarction and cerebral infarction: clinical characteristics, and short-term outcome

PubMed Central

Naess, Halvor; Romi, Fredrik

2011-01-01

Background: To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Methods: Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Results: Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Conclusion: Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis. PMID:21915166

Neurological function after total en bloc spondylectomy for thoracic spinal tumors.

PubMed

Murakami, Hideki; Kawahara, Norio; Demura, Satoru; Kato, Satoshi; Yoshioka, Katsuhito; Tomita, Katsuro

2010-03-01

Total en bloc spondylectomy (TES) for thoracic spinal tumors may in theory produce neurological dysfunction as a result of ischemic or mechanical damage to the spinal cord. Potential insults include preoperative embolization at 3 levels, intraoperative ligation of segmental arteries, nerve root ligation, and circumferential dural dissection. The purpose of this study was to assess neurological function after thoracic TES. The authors performed a retrospective review of 79 patients with thoracic-level spinal tumors that had been treated with TES between 1989 and 2006. Neurological function was retrospectively analyzed according to the Frankel grading system. Of the 79 cases, 26 involved primary tumors and 53 involved metastatic tumors. The number of excised vertebrae was 1 in 60 cases, 2 in 13, and >or= 3 in 6. The Frankel grade before surgery was B in 1 case, C in 16, D in 29, and E in 33. At the follow-up, the Frankel grade was C in 2 cases, D in 24, and E in 53. Of 46 cases with neurological deficits before surgery, neurological improvement of at least 1 Frankel grade was achieved in 25 cases (54.3%). Although the Frankel grade did not change in 21 patients, improvement in neurological symptoms within the same Frankel grade did occur in these patients. There were no cases of neurological deterioration. There was no neurological deterioration due to preoperative embolization, ligation of segmental arteries, or ligation of thoracic nerve roots. Each of the cases with preoperative neurological deficits showed improvement in neurological symptoms. Data in the current study clinically proved that TES is a safe operation with respect to spinal cord blood flow. In TES, the spinal cord is circumferentially decompressed and the spinal column is shortened. An increase in spinal cord blood flow due to spinal shortening in addition to decompression was considered to have brought about a resolution of neurological symptoms with TES.

Association between reliance on devices and people for walking and ability to walk community distances among persons with spinal cord injury.

PubMed

Brotherton, Sandra S; Saunders, Lee L; Krause, James S; Morrisette, David C

2012-05-01

To identify and describe the frequency of reliance on assistive devices and/or people for ambulating distances and stair climbing. Survey. A total of 429 adults with traumatic spinal cord injury who were able to walk at least 10 m were identified through inpatient and outpatient hospital databases at a specialty hospital in the southeast United States. Data were collected using a self-report questionnaire including items related to distances walked and devices used for ambulation. Participants best able to ambulate community distances were those who were independent with ambulation and those who used one cane or crutch. Reliance on people or use of a walker was associated with walking shorter distances. Regression analysis indicated reliance on devices or people for walking predicted variation in ability to ambulate community distances after controlling for demographic and injury characteristics. This study suggests that reliance on devices or a person for assistance is important to consider when assessing potential for achieving functional community ambulation.

Anesthesia for cesarean delivery in an achondroplastic dwarf: a case report.

PubMed

Huang, Jeffrey; Babins, Noah

2008-12-01

There are more than 100 different types of dwarfism. Achondroplasia is the most common form of this rare condition. The incidence of achondroplasia in the United States is about 15 per 1 million births. Although inherited as an autosomal dominant condition, 80% of cases result from spontaneous mutation. Underdevelopment and premature ossification of bones result in characteristic craniofacial and spinal abnormalities. Limited neck extension, foramen magnum stenosis, a large tongue, large mandible, and atlanto-axial instability can lead to increased difficulty of airway management. Severe kyphosis, scoliosis, spinal stenosis, and unpredictable spread of local anesthetics in the epidural space and subarachnoid space lead to reluctance to apply regional anesthesia in this patient group. In addition, pregnancy in a person with achondroplasis poses more problems for anesthetic selection. These problems include potential hypoxia, severely decreased functional residual capacity, risk of gastric aspiration, and supine hypotension. In this case report, we describe the anesthetic management of an achondroplastic dwarf who underwent cesarean delivery.

Motor Neuron Rescue in Spinal Muscular Atrophy Mice Demonstrates That Sensory-Motor Defects Are a Consequence, Not a Cause, of Motor Neuron Dysfunction

PubMed Central

Gogliotti, Rocky G.; Quinlan, Katharina A.; Barlow, Courtenay B.; Heier, Christopher R.; Heckman, C. J.

2012-01-01

The loss of motor neurons (MNs) is a hallmark of the neuromuscular disease spinal muscular atrophy (SMA); however, it is unclear whether this phenotype autonomously originates within the MN. To address this question, we developed an inducible mouse model of severe SMA that has perinatal lethality, decreased motor function, motor unit pathology, and hyperexcitable MNs. Using an Hb9-Cre allele, we increased Smn levels autonomously within MNs and demonstrate that MN rescue significantly improves all phenotypes and pathologies commonly described in SMA mice. MN rescue also corrects hyperexcitability in SMA motor neurons and prevents sensory-motor synaptic stripping. Survival in MN-rescued SMA mice is extended by only 5 d, due in part to failed autonomic innervation of the heart. Collectively, this work demonstrates that the SMA phenotype autonomously originates in MNs and that sensory-motor synapse loss is a consequence, not a cause, of MN dysfunction. PMID:22423102

[Functional rehabilitation of spinal cord injured persons using neuroprostheses].

PubMed

Rupp, R; Abel, R

2005-02-01

Recent technological advancements in microelectronics have led to the establishment of systems for restoration of basic functions in spinal cord injured (SCI) persons using functional electrical stimulation (FES). FES systems for the restoration of bladder and diaphragm function are well established in clinical practice. While FES systems in the lower extremities for standing/walking have not yet achieved widespread clinical acceptance, devices which enhance or restore the grasp function in tetraplegic patients with missing control of hand and fingers are demonstrably successful. Especially with the use of implantable systems a reliable, easy to handle application is possible. The most recent developments in micromechanical engineering are aimed at providing minimally invasive, subminiature systems for functional support in incomplete SCI persons. The possibility of direct brain control of FES systems will expand the application of neuroprostheses for patients with injury of the high cervical spinal cord.

Surgical treatment for old subaxial cervical dislocation with bilateral locked facets in a 3-year-old girl: A case report.

PubMed

Li, Cheng; Li, Lei; Duan, Jingzhu; Zhang, Lijun; Liu, Zhenjiang

2018-05-01

This study aimed to describe the case of a 3-year-old girl with old bilateral facet dislocation on cervical vertebrae 6 and 7, who had spinal cord transection, received surgical treatment, and achieved a relative satisfactory therapeutic effect. A 3-year-old girl was urgently transferred to the hospital after a car accident. DIAGNOSES:: she was diagnosed with splenic rupture, intracranial hemorrhage, cervical dislocation, spinal transection, and Monteggia fracture of the left upper limb. The girl underwent emergency splenectomy and was transferred to the intensive care unit of the hospital 15 days later. One-stage anterior-posterior approach surgery (anterior discectomy, posterior laminectomy, and pedicle screw fixation) was performed when the patient stabilized after 45-day symptomatic treatment. The operation was uneventful. The reduction of lower cervical dislocation was satisfactory, with sufficient spinal cord decompression. The internal fixation position was good, and the spinal sequence was well restored. The girl was discharged 2 weeks later after the operation and followed up for 2 years. The major nerve function of both upper limbs was recovered, with no obvious retardation of the growth of immature spine. A satisfactory therapeutic effect was achieved for a pediatric old subaxial cervical dislocation with bilateral locked facets using anterior discectomy, posterior laminectomy, and pedicle screw fixation. The posterior pedicle screw fixation provided a good three-dimensional stability of the spine, with reduced risk and complications caused by anterior internal fixation. The growth of immature spine was not obviously affected during the 2-year follow-up.

Manual therapy directed at the knee or lumbopelvic region does not influence quadriceps spinal reflex excitability.

PubMed

Grindstaff, Terry L; Pietrosimone, Brian G; Sauer, Lindsay D; Kerrigan, D Casey; Patrie, James T; Hertel, Jay; Ingersoll, Christopher D

2014-08-01

Manual therapies, directed to the knee and lumbopelvic region, have demonstrated the ability to improve neuromuscular quadriceps function in individuals with knee pathology. It remains unknown if manual therapies may alter impaired spinal reflex excitability, thus identifying a potential mechanism in which manual therapy may improve neuromuscular function following knee injury. To determine the effect of local and distant mobilisation/manipulation interventions on quadriceps spinal reflex excitability. Seventy-five individuals with a history of knee joint injury and current quadriceps inhibition volunteered for this study. Participants were randomised to one of five intervention groups: lumbopelvic manipulation (grade V), lumbopelvic manipulation positioning (no thrust), grade IV patellar mobilisation, grade I patellar mobilisation, and control (no treatment). Changes in spinal reflex excitability were quantified by assessing the Hoffmann reflex (H-reflex), presynaptic, and postsynaptic excitability. A hierarchical linear-mixed model for repeated measures was performed to compare changes in outcome variables between groups over time (pre, post 0, 30, 60, 90 min). There were no significant differences in H-reflex, presynaptic, or postsynaptic excitability between groups across time. Manual therapies directed to the knee or lumbopelvic region did not acutely change quadriceps spinal reflex excitability. Although manual therapies may improve impairments and functional outcomes the underlying mechanism does not appear to be related to changes in spinal reflex excitability. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intraspinal serotonergic signaling suppresses locomotor activity in larval zebrafish.

PubMed

Montgomery, Jacob E; Wahlstrom-Helgren, Sarah; Wiggin, Timothy D; Corwin, Brittany M; Lillesaar, Christina; Masino, Mark A

2018-06-19

Serotonin (5HT) is a modulator of many vital processes in the spinal cord (SC), such as production of locomotion. In the larval zebrafish, intraspinal serotonergic neurons (ISNs) are a source of spinal 5HT that, despite the availability of numerous genetic and optical tools, has not yet been directly shown to affect the spinal locomotor network. In order to better understand the functions of ISNs, we used a combination of strategies to investigate ISN development, morphology, and function. ISNs were optically isolated from one another by photoconverting Kaede fluorescent protein in individual cells, permitting morphometric analysis as they developed in vivo. ISN neurite lengths and projection distances exhibited the greatest amount of change between 3 and 4 days post-fertilization (dpf) and appeared to stabilize by 5 dpf. Overall ISN innervation patterns were similar between cells and between SC regions. ISNs possessed rostrally-extending neurites resembling dendrites and a caudally-extending neurite resembling an axon, which terminated with an enlarged growth cone-like structure. Interestingly, these enlargements remained even after neurite extension had ceased. Functionally, application of exogenous 5HT reduced spinally-produced motor nerve bursting. A selective 5HT reuptake inhibitor and ISN activation with channelrhodopsin each produced similar effects to 5HT, indicating that spinally-intrinsic 5HT originating from the ISNs has an inhibitory effect on the spinal locomotor network. Taken together this suggests that the ISNs are morphologically mature by 5 dpf and supports their involvement in modulating the activity of the spinal locomotor network. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Comparison of mesenchymal stem cells derived from fat, bone marrow, Wharton's jelly, and umbilical cord blood for treating spinal cord injuries in dogs.

PubMed

Ryu, Hak-Hyun; Kang, Byung-Jae; Park, Sung-Su; Kim, Yongsun; Sung, Gyu-Jin; Woo, Heung-Myong; Kim, Wan Hee; Kweon, Oh-Kyeong

2012-12-01

Previous animal studies have shown that transplantation of mesenchymal stem cells (MSCs) into spinal cord lesions enhances axonal regeneration and promotes functional recovery. We isolated the MSCs derived from fat, bone marrow, Wharton's jelly and umbilical cord blood (UCB) positive for MSC markers and negative for hematopoietic cell markers. Their effects on the regeneration of injured canine spinal cords were compared. Spinal cord injury was induced by balloon catheter compression. Dogs with injured spinal cords were treated with only matrigel or matrigel mixed with each type of MSCs. Olby and modified Tarlov scores, immunohistochemistry, ELISA and Western blot analysis were used to evaluate the therapeutic effects. The different MSC groups showed significant improvements in locomotion at 8 weeks after transplantation (P<0.05). This recovery was accompanied by increased numbers of surviving neuron and neurofilament-positive fibers in the lesion site. Compared to the control, the lesion sizes were smaller, and fewer microglia and reactive astrocytes were found in the spinal cord epicenter of all MSC groups. Although there were no significant differences in functional recovery among the MSCs groups, UCB-derived MSCs (UCSCs) induced more nerve regeneration and anti-inflammation activity (P<0.05). Transplanted MSCs survived for 8 weeks and reduced IL-6 and COX-2 levels, which may have promoted neuronal regeneration in the spinal cord. Our data suggest that transplantation of MSCs promotes functional recovery after SCI. Furthermore, application of UCSCs led to more nerve regeneration, neuroprotection and less inflammation compared to other MSCs.

Fertility and sexuality in the spinal cord injury patient.

PubMed

Stoffel, J T; Van der Aa, F; Wittmann, D; Yande, S; Elliott, S

2018-06-14

After a spinal cord injury, patients have different perceptions of sexuality, sexual function, and potential for fertility. These changes can greatly impact quality of life over a lifetime. The purpose of this workgroup was to identify common evidence based or expert opinion themes and recommendations regarding treatment of sexuality, sexual function and fertility in the spinal cord injury population. As part of the SIU-ICUD joint consultation of Urologic Management of the Spinal Cord Injury (SCI), a workgroup and comprehensive literature search of English language manuscripts regarding fertility and sexuality in the spinal cord injury patient were formed. Articles were compiled, and recommendations in the chapter are based on group discussion and follow the Oxford Centre for Evidence-based Medicine system for levels of evidence (LOEs) and grades of recommendation (GORs). Genital arousal, ejaculation, and orgasm are significantly impacted after spinal cord injury in both male and female SCI patients. This may have a more significant impact on potential for fertility in male spinal cord injury patients, particularly regarding ability of generate erection, semen quantity and quality. Female patients should be consulted that pregnancy is still possible after injury and a woman should expect resumption of normal reproductive function. As a result, sexual health teaching should be continued in women despite injury. Pregnancy in a SCI may cause complications such as autonomic dysreflexia, so this group should be carefully followed during pregnancy. By understanding physiologic changes after injury, patients and care teams can work together to achieve goals and maximize sexual quality of life after the injury.

Spinal deformities rehabilitation - state of the art review.

PubMed

Weiss, Hans-Rudolf

2010-12-24

Medical rehabilitation aims at an improvement in function, capacity and participation. For the rehabilitation of spinal deformities, the goal is to maintain function and prevent secondary symptoms in the short- and long-term. In patients with scoliosis, predictable signs and symptoms include pain and reduced pulmonary function. A Pub Med review was completed in order to reveal substantial evidence for inpatient rehabilitation as performed in Germany. No evidence has been found in general to support claims for actual inpatient rehabilitation programmes as used today. Nevertheless, as there is some evidence that inpatient rehabilitation may be beneficial to patients with spinal deformities complicated by certain additional conditions, the body of evidence there is for conservative treatment of spinal deformities has been reviewed in order to allow suggestions for outpatient conservative treatment and inpatient rehabilitation. Today, for both children and adolescents, we are able to offer intensive rehabilitation programmes lasting three to five days, which enable the patients to acquire the skills necessary to prevent postures fostering scoliosis in everyday life without missing too much of school teaching subjects at home. The secondary functional impairments adult scoliosis patients might have, as in the opinion of the author, still today require the time of 3-4 weeks in the clinical in-patient setting. Time to address psychosocial as well as somatic limitations, namely chronic pains and cardiorespiratory malfunction is needed to preserve the patients working capability in the long-term. Outpatient treatment/rehabilitation is sufficient for adolescents with spinal deformities.Inpatient rehabilitation is recommended for patients with spinal deformities and pain or severe restrictive ventilation disorder.

Early gene expression during natural spinal cord regeneration in the salamander Ambystoma mexicanum.

PubMed

Monaghan, James R; Walker, John A; Page, Robert B; Putta, Srikrishna; Beachy, Christopher K; Voss, S Randal

2007-04-01

In contrast to mammals, salamanders have a remarkable ability to regenerate their spinal cord and recover full movement and function after tail amputation. To identify genes that may be associated with this greater regenerative ability, we designed an oligonucleotide microarray and profiled early gene expression during natural spinal cord regeneration in Ambystoma mexicanum. We sampled tissue at five early time points after tail amputation and identified genes that registered significant changes in mRNA abundance during the first 7 days of regeneration. A list of 1036 statistically significant genes was identified. Additional statistical and fold change criteria were applied to identify a smaller list of 360 genes that were used to describe predominant expression patterns and gene functions. Our results show that a diverse injury response is activated in concert with extracellular matrix remodeling mechanisms during the early acute phase of natural spinal cord regeneration. We also report gene expression similarities and differences between our study and studies that have profiled gene expression after spinal cord injury in rat. Our study illustrates the utility of a salamander model for identifying genes and gene functions that may enhance regenerative ability in mammals.

Willingness to Pay for a Newborn Screening Test for Spinal Muscular Atrophy.

PubMed

Lin, Pei-Jung; Yeh, Wei-Shi; Neumann, Peter J

2017-01-01

The current US mandatory newborn screening panel does not include spinal muscular atrophy, the most common fatal genetic disease among children. We assessed population preferences for newborn screening for spinal muscular atrophy, and how test preferences varied depending on immediate treatment implications. We conducted an online willingness-to-pay survey of US adults (n = 982). Respondents were asked to imagine being parents of a newborn. Each respondent was presented with two hypothetical scenarios following the spinal muscular atrophy screening test: current standard of care (no treatment available) and one of three randomly assigned scenarios (new treatment available to improve functioning, survival, or both). We used a bidding game to elicit willingness to pay for the spinal muscular atrophy test, and performed a two-part model to estimate median and mean willingness-to-pay values. Most respondents (79% to 87%) would prefer screening their newborns for spinal muscular atrophy. People expressed a willingness to pay for spinal muscular atrophy screening even without an available therapy (median: $142; mean: $253). Willingness to pay increased with treatment availability (median: $161 to $182; mean: $270 to $297) and respondent income. Most respondents considered test accuracy, treatment availability, and treatment effectiveness very important or important factors in deciding willingness to pay. Most people would prefer and would be willing to pay for testing their newborn for spinal muscular atrophy, even in the absence of direct treatment. People perceive the spinal muscular atrophy test more valuable if treatment were available to improve the newborn's functioning and survival. Despite preferences for the test information, adding spinal muscular atrophy to newborn screening programs remains controversial. Future studies are needed to determine how early detection may impact long-term patient outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

The Associations Between Physical Therapy and Long-Term Outcomes for Individuals with Lumbar Spinal Stenosis in the SPORT study

PubMed Central

Fritz, Julie M.; Lurie, Jon D.; Zhao, Wenyan; Whitman, Julie M.; Delitto, Anthony; Brennan, Gerard P.; Weinstein, James N.

2013-01-01

Background/Context A period of non-surgical management is advocated prior to surgical treatment for most patients with lumbar spinal stenosis. Currently, little evidence is available to define optimal non-surgical management. Physical therapy is often used, however its use and effectiveness relative to other non-surgical strategies has not been adequately explored. Purpose Describe the utilization of physical therapy and other non-surgical interventions by patients with lumbar spinal stenosis and examine the relationship between physical therapy and long-term prognosis. Study Design Secondary analysis of the Spine Patient Outcomes Research Trial (SPORT) combining data from randomized and observational studies. Setting 13 spine clinics in 11 states in the United States. Patient Sample Patients with lumbar spinal stenosis receiving non-surgical management including those who did or did not receive physical therapy within 6 weeks of enrollment. Outcome Measures Primary outcome measures included cross-over to surgery, the bodily pain and physical function scales changes from the Survey Short Form 36 (SF-36), and the modified Oswestry Disability Index. Secondary outcome measures were patient satisfaction and the Sciatica Bothersomeness Index. Methods Baseline characteristics and rates of cross-over to surgery were compared between patients who did or did not receive physical therapy. Baseline factors predictive of receiving physical therapy were examined with logistic regression. Mixed effects models were used to compare outcomes between groups at 3 and 6 months, and 1 year after enrollment adjusted for baseline severity and patient characteristics. Results Physical therapy was used in the first 6 weeks by 90 of 244 patients (37%) and was predicted by the absence of radiating pain and being single instead of married. Physical therapy was associated with a reduced likelihood of cross-over to surgery after 1 year (21% vs 33%, p=0.045), and greater reductions on the SF-36 physical functioning scale after 6 months (mean difference =6.0, 95% CI: 0.2, 11.7) and 1 year (mean difference =6.5, 95% CI: 0.6, 12.4). There were no differences in bodily pain or Oswestry scores across time. Conclusion Many patients with lumbar spinal stenosis pursuing conservative management receive physical therapy. Using physical therapy was associated with reduced likelihood of patients receiving surgery within 1 year. Results for other outcomes were mixed with no differences in several measures. Further research is needed to examine the effectiveness of physical therapy relative to other non-surgical management strategies for patients with lumbar spinal stenosis. PMID:24373681

Transplantation of human immature dental pulp stem cell in dogs with chronic spinal cord injury.

PubMed

Feitosa, Matheus Levi Tajra; Sarmento, Carlos Alberto Palmeira; Bocabello, Renato Zonzini; Beltrão-Braga, Patrícia Cristina Baleeiro; Pignatari, Graciela Conceição; Giglio, Robson Fortes; Miglino, Maria Angelica; Orlandin, Jéssica Rodrigues; Ambrósio, Carlos Eduardo

2017-07-01

To investigate the therapeutic potential of human immature dental pulp stem cells in the treatment of chronic spinal cord injury in dogs. Three dogs of different breeds with chronic SCI were presented as animal clinical cases. Human immature dental pulp stem cells were injected at three points into the spinal cord, and the animals were evaluated by limb function and magnetic resonance imaging (MRI) pre and post-operative. There was significant improvement from the limb function evaluated by Olby Scale, though it was not supported by the imaging data provided by MRI and clinical sign and evaluation. Human dental pulp stem cell therapy presents promising clinical results in dogs with chronic spinal cord injuries, if used in association with physical therapy.

[Anesthesia for surgery of degenerative and abnormal cervical spine].

PubMed

Béal, J L; Lopin, M C; Binnert, M

1993-01-01

A feature common to all congenital or inflammatory abnormalities of the cervical spine is an actual or potential reduction in the lumen of the spinal canal. The spinal cord and nerve roots are at risk. During intubation, and positioning the patient on the table, all untoward movements of the cervical spine may lead to spinal cord compression. Abnormalities of the cervical spine carry the risk of a difficult intubation. If there is much debate as to what constitutes optimum management of the airway, there is no evidence that any one method is the best. Recognizing the possible instability and intubating with care, are probably much more important in preserving neurological function than any particular mode of intubation. During maintenance of anaesthesia, the main goal is to preserve adequate spinal cord perfusion in order to prevent further damage. Spinal cord blood flow seems to be regulated by the same factors as cerebral blood flow. Hypercapnia increases cord blood flow while hypocapnia decreases it. Therefore, normocapnia or mild hypocapnia is recommended. Induced hypotension is frequently used to decrease blood loss. However, in patients with a marginally perfused spinal cord, the reduction in blood flow may cause ischaemia of the spinal cord and may therefore be relatively contraindicated. In addition to standard intraoperative monitoring, spinal cord monitoring is almost mandatory. Monitoring somatosensory evoked potentials is used routinely. However, the major limitation is that this technique only monitors dorsal column function; theoretically, motor paralysis can occur despite a lack of change in recorded signals. Neurogenic motor evoked potentials may now be used to monitor anterior spinal cord integrity.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuroprotective effects of Ganoderma lucidum polysaccharides against traumatic spinal cord injury in rats.

PubMed

Gokce, Emre Cemal; Kahveci, Ramazan; Atanur, Osman Malik; Gürer, Bora; Aksoy, Nurkan; Gokce, Aysun; Sargon, Mustafa Fevzi; Cemil, Berker; Erdogan, Bulent; Kahveci, Ozan

2015-11-01

Ganoderma lucidum (G. lucidum) is a mushroom belonging to the polyporaceae family of Basidiomycota and has widely been used as a traditional medicine for thousands of years. G. lucidum has never been studied in traumatic spinal cord injury. The aim of this study is to investigate whether G. lucidum polysaccharides (GLPS) can protect the spinal cord after experimental spinal cord injury. Rats were randomized into five groups of eight animals each: control, sham, trauma, GLPS, and methylprednisolone. In the control group, no surgical intervention was performed. In the sham group, only a laminectomy was performed. In all the other groups, the spinal cord trauma model was created by the occlusion of the spinal cord with an aneurysm clip. In the spinal cord tissue, caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, nitric oxide levels, and superoxide dismutase levels were analysed. Histopathological and ultrastructural evaluations were also performed. Neurological evaluation was performed using the Basso, Beattie, and Bresnahan locomotor scale and the inclined-plane test. After traumatic spinal cord injury, increases in caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels were detected. After the administration of GLPS, decreases were observed in tissue caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels. Furthermore, GLPS treatment showed improved results in histopathological scores, ultrastructural scores, and functional tests. Biochemical, histopathological, and ultrastructural analyses and functional tests reveal that GLPS exhibits meaningful neuroprotective effects against spinal cord injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human neural progenitors differentiate into astrocytes and protect motor neurons in aging rats.

PubMed

Das, Melanie M; Avalos, Pablo; Suezaki, Patrick; Godoy, Marlesa; Garcia, Leslie; Chang, Christine D; Vit, Jean-Philippe; Shelley, Brandon; Gowing, Genevieve; Svendsen, Clive N

2016-06-01

Age-associated health decline presents a significant challenge to healthcare, although there are few animal models that can be used to test potential treatments. Here, we show that there is a significant reduction in both spinal cord motor neurons and motor function over time in the aging rat. One explanation for this motor neuron loss could be reduced support from surrounding aging astrocytes. Indeed, we have previously shown using in vitro models that aging rat astrocytes are less supportive to rat motor neuron function and survival over time. Here, we test whether rejuvenating the astrocyte niche can improve the survival of motor neurons in an aging spinal cord. We transplanted fetal-derived human neural progenitor cells (hNPCs) into the aging rat spinal cord and found that the cells survive and differentiate into astrocytes with a much higher efficiency than when transplanted into younger animals, suggesting that the aging environment stimulates astrocyte maturation. Importantly, the engrafted astrocytes were able to protect against motor neuron loss associated with aging, although this did not result in an increase in motor function based on behavioral assays. We also transplanted hNPCs genetically modified to secrete glial cell line-derived neurotrophic factor (GDNF) into the aging rat spinal cord, as this combination of cell and protein delivery can protect motor neurons in animal models of ALS. During aging, GDNF-expressing hNPCs protected motor neurons, though to the same extent as hNPCs alone, and again had no effect on motor function. We conclude that hNPCs can survive well in the aging spinal cord, protect motor neurons and mature faster into astrocytes when compared to transplantation into the young spinal cord. While there was no functional improvement, there were no functional deficits either, further supporting a good safety profile of hNPC transplantation even into the older patient population. Copyright © 2016 Elsevier Inc. All rights reserved.

Intraspinal microstimulation and diaphragm activation after cervical spinal cord injury

PubMed Central

Mercier, L. M.; Gonzalez-Rothi, E. J.; Streeter, K. A.; Posgai, S. S.; Poirier, A. S.; Fuller, D. D.; Reier, P. J.

2016-01-01

Intraspinal microstimulation (ISMS) using implanted electrodes can evoke locomotor movements after spinal cord injury (SCI) but has not been explored in the context of respiratory motor output. An advantage over epidural and direct muscle stimulation is the potential of ISMS to selectively stimulate components of the spinal respiratory network. The present study tested the hypothesis that medullary respiratory activity could be used to trigger midcervical ISMS and diaphragm motor unit activation in rats with cervical SCI. Studies were conducted after acute (hours) and subacute (5–21 days) C2 hemisection (C2Hx) injury in adult rats. Inspiratory bursting in the genioglossus (tongue) muscle was used to trigger a 250-ms train stimulus (100 Hz, 100–200 μA) to the ventral C4 spinal cord, targeting the phrenic motor nucleus. After both acute and subacute injury, genioglossus EMG activity effectively triggered ISMS and activated diaphragm motor units during the inspiratory phase. The ISMS paradigm also evoked short-term potentiation of spontaneous inspiratory activity in the previously paralyzed hemidiaphragm (i.e., bursting persisting beyond the stimulus period) in ∼70% of the C2Hx animals. We conclude that medullary inspiratory output can be used to trigger cervical ISMS and diaphragm activity after SCI. Further refinement of this method may enable “closed-loop-like” ISMS approaches to sustain ventilation after severe SCI. NEW & NOTEWORTHY We examined the feasibility of using intraspinal microstimulation (ISMS) of the cervical spinal cord to evoke diaphragm activity ipsilateral to acute and subacute hemisection of the upper cervical spinal cord of the rat. This proof-of-concept study demonstrated the efficacy of diaphragm activation, using an upper airway respiratory EMG signal to trigger ISMS at the level of the ipsilesional phrenic nucleus during acute and advanced postinjury intervals. PMID:27881723

Nationwide incidence of serious complications of epidural analgesia in the United States.

PubMed

Rosero, E B; Joshi, G P

2016-07-01

This study aimed to describe the incidence and risk factors of in-hospital spinal hematoma and abscess associated with epidural analgesia in adult obstetric and non-obstetric populations in the United States. The Nationwide Inpatient Sample was analyzed to identify patients receiving epidural analgesia from 1998 to 2010. Primary outcomes were incidence of spinal hematoma and epidural abscess. Use of decompressive laminectomy was also investigated. Regression analyses were conducted to assess predictors of epidural analgesia complications. Differences in mortality and disposition of patients at discharge were compared in patients with and without neuraxial complications. Obstetric and non-obstetric patients were studied separately. A total of 3,703,755 epidural analgesia procedures (2,320,950 obstetric and 1,382,805 non-obstetric) were identified. In obstetric patients, the incidence of spinal hematoma was 0.6 per 100,000 epidural catheterizations (95% CI, 0.3 to 1.0 × 10(-5) ). The incidence of epidural abscess was zero. In non-obstetric patients, the incidence of spinal hematoma and epidural abscess were, respectively, 18.5 per 100,000 (95% CI, 16.3 to 20.9 × 10(-5) ) and 7.2 per 100,000 (95% CI, 5.8 to 8.7 × 10(-5) ) catheterizations. Predictors of spinal hematoma included type of surgical procedure (higher in vascular surgery), teaching status of hospital, and comorbidity score. Patients with spinal complications had higher in-hospital mortality (12.2% vs. 1.1%, P < 0.0001) and were significantly less likely to be discharged to home. This large nationwide data analysis reveals that the incidence of epidural analgesia-related complications is very low in obstetric population epidural analgesia and much higher in patients having vascular surgery. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Interventional spinal procedures guided and controlled by a 3D rotational angiographic unit.

PubMed

Pedicelli, Alessandro; Verdolotti, Tommaso; Pompucci, Angelo; Desiderio, Flora; D'Argento, Francesco; Colosimo, Cesare; Bonomo, Lorenzo

2011-12-01

The aim of this paper is to demonstrate the usefulness of 2D multiplanar reformatting images (MPR) obtained from rotational acquisitions with cone-beam computed tomography technology during percutaneous extra-vascular spinal procedures performed in the angiography suite. We used a 3D rotational angiographic unit with a flat panel detector. MPR images were obtained from a rotational acquisition of 8 s (240 images at 30 fps), tube rotation of 180° and after post-processing of 5 s by a local work-station. Multislice CT (MSCT) is the best guidance system for spinal approaches permitting direct tomographic visualization of each spinal structure. Many operators, however, are trained with fluoroscopy, it is less expensive, allows real-time guidance, and in many centers the angiography suite is more frequently available for percutaneous procedures. We present our 6-year experience in fluoroscopy-guided spinal procedures, which were performed under different conditions using MPR images. We illustrate cases of vertebroplasty, epidural injections, selective foraminal nerve root block, facet block, percutaneous treatment of disc herniation and spine biopsy, all performed with the help of MPR images for guidance and control in the event of difficult or anatomically complex access. The integrated use of "CT-like" MPR images allows the execution of spinal procedures under fluoroscopy guidance alone in all cases of dorso-lumbar access, with evident limitation of risks and complications, and without need for recourse to MSCT guidance, thus eliminating CT-room time (often bearing high diagnostic charges), and avoiding organizational problems for procedures that need, for example, combined use of a C-arm in the CT room.

Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic Rehabilitation: Elements of Success, Failure, and Dependence

PubMed Central

Udoekwere, Ubong I.; Oza, Chintan S.

2016-01-01

Robot therapy promotes functional recovery after spinal cord injury (SCI) in animal and clinical studies. Trunk actions are important in adult rats spinalized as neonates (NTX rats) that walk autonomously. Quadrupedal robot rehabilitation was tested using an implanted orthosis at the pelvis. Trunk cortical reorganization follows such rehabilitation. Here, we test the functional outcomes of such training. Robot impedance control at the pelvis allowed hindlimb, trunk, and forelimb mechanical interactions. Rats gradually increased weight support. Rats showed significant improvement in hindlimb stepping ability, quadrupedal weight support, and all measures examined. Function in NTX rats both before and after training showed bimodal distributions, with “poor” and “high weight support” groupings. A total of 35% of rats initially classified as “poor” were able to increase their weight-supported step measures to a level considered “high weight support” after robot training, thus moving between weight support groups. Recovered function in these rats persisted on treadmill with the robot both actuated and nonactuated, but returned to pretraining levels if they were completely disconnected from the robot. Locomotor recovery in robot rehabilitation of NTX rats thus likely included context dependence and/or incorporation of models of robot mechanics that became essential parts of their learned strategy. Such learned dependence is likely a hurdle to autonomy to be overcome for many robot locomotor therapies. Notwithstanding these limitations, trunk-based quadrupedal robot rehabilitation helped the rats to visit mechanical states they would never have achieved alone, to learn novel coordinations, and to achieve major improvements in locomotor function. SIGNIFICANCE STATEMENT Neonatal spinal transected rats without any weight support can be taught weight support as adults by using robot rehabilitation at trunk. No adult control rats with neonatal spinal transections spontaneously achieve similar changes. The robot rehabilitation system can be inactivated and the skills that were learned persist. Responding rats cannot be detached from the robot altogether, a dependence develops in the skill learned. From data and analysis here, the likelihood of such rats to respond to the robot therapy can also now be predicted. These results are all novel. Understanding trunk roles in voluntary and spinal reflex integration after spinal cord injury and in recovery of function are broadly significant for basic and clinical understanding of motor function. PMID:27511008

Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic Rehabilitation: Elements of Success, Failure, and Dependence.

PubMed

Udoekwere, Ubong I; Oza, Chintan S; Giszter, Simon F

2016-08-10

Robot therapy promotes functional recovery after spinal cord injury (SCI) in animal and clinical studies. Trunk actions are important in adult rats spinalized as neonates (NTX rats) that walk autonomously. Quadrupedal robot rehabilitation was tested using an implanted orthosis at the pelvis. Trunk cortical reorganization follows such rehabilitation. Here, we test the functional outcomes of such training. Robot impedance control at the pelvis allowed hindlimb, trunk, and forelimb mechanical interactions. Rats gradually increased weight support. Rats showed significant improvement in hindlimb stepping ability, quadrupedal weight support, and all measures examined. Function in NTX rats both before and after training showed bimodal distributions, with "poor" and "high weight support" groupings. A total of 35% of rats initially classified as "poor" were able to increase their weight-supported step measures to a level considered "high weight support" after robot training, thus moving between weight support groups. Recovered function in these rats persisted on treadmill with the robot both actuated and nonactuated, but returned to pretraining levels if they were completely disconnected from the robot. Locomotor recovery in robot rehabilitation of NTX rats thus likely included context dependence and/or incorporation of models of robot mechanics that became essential parts of their learned strategy. Such learned dependence is likely a hurdle to autonomy to be overcome for many robot locomotor therapies. Notwithstanding these limitations, trunk-based quadrupedal robot rehabilitation helped the rats to visit mechanical states they would never have achieved alone, to learn novel coordinations, and to achieve major improvements in locomotor function. Neonatal spinal transected rats without any weight support can be taught weight support as adults by using robot rehabilitation at trunk. No adult control rats with neonatal spinal transections spontaneously achieve similar changes. The robot rehabilitation system can be inactivated and the skills that were learned persist. Responding rats cannot be detached from the robot altogether, a dependence develops in the skill learned. From data and analysis here, the likelihood of such rats to respond to the robot therapy can also now be predicted. These results are all novel. Understanding trunk roles in voluntary and spinal reflex integration after spinal cord injury and in recovery of function are broadly significant for basic and clinical understanding of motor function. Copyright © 2016 the authors 0270-6474/16/368341-15$15.00/0.

History of the treatment of spinal injuries.

PubMed

Silver, J R

2005-02-01

Injury of the spinal cord has been known since antiquity. There is no cure for the injury and until modern times patients died rapidly from a combination of pressure sores and urinary tract infection. Treatment consists of preventing complications until the spine has stabilised and the patient can be rehabilitated to an independent life. This article explores how this treatment developed in the ancient world, the middle ages, in Europe, Great Britain, and latterly in the United States. It describes how these principles of treatment were recognised particularly in Germany, the United States, and Great Britain and evaluates the relative contributions made by the different pioneers.

Evaluation of Staff’s Job Satisfaction in the Spinal Cord Unit in Italy

PubMed Central

Laura, Cominetti; Lorenza, Garrino; Rita, Decorte; Nadia, Felisi; Ebe, Matta; Vittoria, Actis Maria; Roberto, Carone; Silvano, Gregorino; Valerio, Dimonte

2013-01-01

In July 2007 a Spinal Cord Unit was set up in Turin (Italy) within the newly integrated structure of the Orthopaedic Traumatologic Centre, warranting a multidisciplinary and professional approach according to International Guidelines. This approach will be possible through experimentation of a personalized care model. To analyze job satisfaction of health care professionals operating within the Spinal Cord Unit, preliminary to organizational change. Data collection was carried out by using questionnaires, interviews, shadowing. Results from quantitative analysis on the self-filled questionnaires were integrated with results from qualitative analysis. All the health care professionals operating in the field were involved. Positive aspects were the perception of carrying out a useful job, the feeling of personal fulfilment and the wish to engage new energies and resources. Problematic aspects included role conflict among staff categories and communication with managers. The positive aspects can be exploited to create professional practices facilitating role and expertise integration, information spreading and staff identification within the organization rather than team work. Data of job satisfaction and self efficacy of health care workers can be considered basic requirement before implementing an organizational change. The main challenges is multiprofessional collaboration. PMID:23750186

Changes in neuronal properties and spinal reflexes during development of spasticity following spinal cord lesions and stroke: studies in animal models and patients.

PubMed

Hultborn, Hans

2003-05-01

It is a well-known fact that spinal reflexes may gradually change and often become enhanced following spinal cord lesions. Although these phenomena are known, the underlying mechanisms are still unknown and under investigation, mainly in animal models. Over the last twenty years, new methods have been developed that can reliably estimate the activity of specific spinal pathways in humans at rest and during voluntary movement. These methods now make it possible to describe components of the spinal pathophysiology in spasticity in humans following spinal lesions or stroke. We now know that spinal networks are capable of generating the basic pattern of locomotion in a large number of vertebrates, including the monkey--and in all likelihood, humans. Although spinal networks are capable of generating locomotor-like activity in the absence of afferent signals, functional gait is not possible without sensory feedback. The results of animal studies on the sensory control of and the transmitter systems involved in the spinal locomotor centers are now being used to improve rehabilitation of walking in persons with spinal cord injury and hemiplegia.

Improving Survival and Promoting Respiratory Motor Function after Cervical Spinal Cord Injury

DTIC Science & Technology

2016-09-01

AWARD NUMBER: W81XWH-15-1-0378 TITLE: Improving Survival and Promoting Respiratory Motor Function after Cervical Spinal Cord Injury PRINCIPAL...Aug 2015 - 14 Aug 2016 4. TITLE AND SUBTITLE CordCorInjury 5a. CONTRACT NUMBER Improvi g Survival and Promoting Respiratory Motor Function After... respiratory complications. This application proposes to help improve survival, decrease early dependence on mechanical ventilation, and restore breathing

More preoperative flexibility implies adequate neural pliability for curve correction without prophylactic untethering in scoliosis patients with asymptomatic tethered spinal cord, a retrospective study.

PubMed

Zhou, Zhenhai; Zhang, Hongqi; Guo, Chaofeng; Yu, Honggui; Wang, Longjie; Guo, Qiang

2017-06-15

Tethered spinal cord is frequently associated with scoliosis. It is still controversial whether a prophylactic untethering is necessary before correction procedure in scoliosis patients with tethered spinal cord. In this study we determined the clinical outcome of a one-stage posterior scoliosis correction without a prophylactic untethering for treating scoliosis with an asymptomatic tethered spinal cord. Seventeen (5 males and 12 females) scoliosis patients with tethered spinal cords were retrospectively reviewed. All patients underwent a one-stage posterior scoliosis correction without preventive untethering. Parameters of radiograph were used to assess correction result. The Scoliosis Research Society (SRS)-22 questionnaire was analyzed pre- and post-operatively to evaluate the clinical outcomes. The modified Japanese Orthopaedic Association (mJOA) score was used to assess the pre- and post-operative spinal cord function. The post-operative coronal Cobb angle was significantly decreased compared with preoperative. (23.8 ± 6.4° vs. 58.4 ± 12.6°, P < 0.01). The coronal Cobb angle was 22.4 ± 6.8° at the final follow-up evaluation. The apical vertebral translation (AVT) was also decreased significantly. (27.5 mm vs. 60.9 mm, P < 0.01). The SRS-22 total score was improved at the 1-year follow-up evaluation compared with the pre-operative SRS-22 total score (87 ± 4 vs. 70 ± 5, p < 0.05). The functional activities, pain, self-image, mental health, and surgery satisfactory scores at the final follow-up evaluation were all improved compared with the corresponding pre-operative scores, especially the self-image and mental health scores (p < 0.05). The spinal cord function was stable and there was no new neurological symptoms after scoliosis correction. No difference existed between the pre- and post-operative total mJOA score (26 ± 2 vs. 27 ± 2, p = 0.39), which including subjective symptom (p = 0.07), clinical symptom (p = 0.33), daily activities (p = 0.44) and bladder function (p = 0.67). One-stage posterior scoliosis correction is a safe and effective surgical procedure for scoliosis patients combined with asymptomatic tethered spinal cord who have adequate spinal cord function reserve.

Measuring body structures and body functions from the International Classification of Functioning, Disability, and Health perspective: considerations for biomedical parameters in spinal cord injury research.

PubMed

Eriks-Hoogland, Inge E; Brinkhof, Martin W G; Al-Khodairy, Abdul; Baumberger, Michael; Brechbühl, Jörg; Curt, Armin; Mäder, Mark; Stucki, Gerold; Post, Marcel W M

2011-11-01

The aims of this study were to provide a selection of biomedical domains based on the comprehensive International Classification of Functioning, Disability, and Health (ICF) core sets for spinal cord injury (SCI) and to present an overview of the corresponding measurement instruments. Based on the Biomedical Domain Set, the SCI literature, the International Spinal Cord Society international data sets, and the Spinal Cord Injury Rehabilitation Evidence project publications were used to derive category specifications for use in SCI research. Expert opinion was used to derive a priority selection. The same sources were used to determine candidate measurement instruments for the specification of body functions and body structures using an example, and guiding principles were applied to select the most appropriate biomedical measurement instrument(s) for use in an SCI research project. Literature searches were performed for 41 second-level ICF body functions categories and for four second-level ICF body structures categories. For some of these categories, only a few candidate measurement instruments were found with limited variation in the type of measurement instruments. An ICF-based measurement set for biomedical aspects of functioning with SCI was established. For some categories of the ICF core sets for SCI, there is a need to develop measurement instruments.

NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury

PubMed Central

Yang, Zhaoyang; Zhang, Aifeng; Duan, Hongmei; Zhang, Sa; Hao, Peng; Ye, Keqiang; Sun, Yi E.; Li, Xiaoguang

2015-01-01

Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial, when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury. PMID:26460015

Neural pathways for colorectal control, relevance to spinal cord injury and treatment: a narrative review.

PubMed

Callaghan, Brid; Furness, John B; Pustovit, Ruslan V

2018-03-01

Narrative review. The purpose is to review the organisation of the nerve pathways that control defecation and to relate this knowledge to the deficits in colorectal function after SCI. A literature review was conducted to identify salient features of defecation control pathways and the functional consequences of damage to these pathways in SCI. The control pathways for defecation have separate pontine centres under cortical control that influence defecation. The pontine centres connect, separately, with autonomic preganglionic neurons of the spinal defecation centres and somatic motor neurons of Onuf's nucleus in the sacral spinal cord. Organised propulsive motor patterns can be generated by stimulation of the spinal defecation centres. Activation of the somatic neurons contracts the external sphincter. The analysis aids in interpreting the consequences of SCI and predicts therapeutic strategies. Analysis of the bowel control circuits identifies sites at which bowel function may be modulated after SCI. Colokinetic drugs that elicit propulsive contractions of the colorectum may provide valuable augmentation of non-pharmacological bowel management procedures.

Clinical application of the Panjabi neutral zone hypothesis: the Stabilimax NZ posterior lumbar dynamic stabilization system.

PubMed

Yue, James J; Timm, Jens P; Panjabi, Manohar M; Jaramillo-de la Torre, Jorge

2007-01-15

The neutral zone (NZ) is a region of intervertebral motion around the neutral posture where little resistance is offered by the passive spinal column. The NZ appears to be a clinically important measure of spinal stability function. Its size may increase with injury to the spinal column, which in turn may result in spinal instability or low-back pain. Dynamic stabilization systems are designed to support and stabilize the spine while maintaining range of motion (ROM). The Stabilimax NZ device has been designed to reduce the NZ after spinal injury to treat pain while preserving ROM.

A comprehensive review of the sub-axial ligaments of the vertebral column: part I anatomy and function.

PubMed

Butt, Asma Mian; Gill, Clarence; Demerdash, Amin; Watanabe, Koichi; Loukas, Marios; Rozzelle, Curtis J; Tubbs, R Shane

2015-07-01

As important as the vertebral ligaments are in maintaining the integrity of the spinal column and protecting the contents of the spinal canal, a single detailed review of their anatomy and function is missing in the literature. A literature search using online search engines was conducted. Single comprehensive reviews of the spinal ligaments are not found in the extant medical literature. This review will be useful to those who treat patients with pathology of the spine or who interpret imaging or investigate the anatomy of the ligaments of the vertebral column.

Sexual satisfaction in women with spinal cord injuries.

PubMed

Otero-Villaverde, S; Ferreiro-Velasco, M E; Montoto-Marqués, A; Salvador de la Barrera, S; Arias-Pardo, A I; Rodriguez-Sotillo, A

2015-07-01

Structured interview based on a predesigned survey. To examine the factors that affect the degree of sexual satisfaction in a sample of women with spinal cord injury (SCI). The study participants were women with SCIs, from the area of the SCI Unit of A Coruña, a reference unit for the Community of Galicia in the northwest of Spain. All study participants were selected consecutively in the outpatient clinic in 2013. The study included women with the American Spinal Injury Association (ASIA) A-D spinal injuries, between the ages of 18 and 65 years, who completed rehabilitation therapy and live in the community. A total of 32 women formed the final study group. When comparing the group of women who were sexually active with those who were not, variables such as age, neurological level, time since the SCI, ASIA or Spinal Cord Independence Measure score, urinary incontinence, chronic pain and spasticity were not related to sexual activity. The only factors that we found to be related to sexual activity were not having a stable partner (P=0.017) and a lack of sensation in the genital area (P=0.039). The only variables related to sexual activity were not having a partner and a lack of sensation in the genital area. Improving sexual satisfaction, information and specific programs during rehabilitation can help women with SCI explore and investigate new erotic possibilities, thereby improving their self-esteem and social relationships.

Bipedal locomotion of bonnet macaques after spinal cord injury.

PubMed

Babu, Rangasamy Suresh; Anand, P; Jeraud, Mathew; Periasamy, P; Namasivayam, A

2007-10-01

Experimental studies concerning the analysis of locomotor behavior in spinal cord injury research are widely performed in rodent models. The purpose of this study was to quantitatively evaluate the degree of functional recovery in reflex components and bipedal locomotor behavior of bonnet macaques (Macaca radiata) after spinal contusive injury. Six monkeys were tested for various reflex components (grasping, righting, hopping, extension withdrawal) and were trained preoperatively to walk in bipedal fashion on the simple and complex locomotor runways (narrow beam, grid, inclined plane, treadmill) of this investigation. The overall performance of the animals'motor behavior and the functional status of limb movements during bipedal locomotion were graded by the Combined Behavioral Score (CBS) system. Using the simple Allen weight-drop technique, a contusive injury was produced by dropping a 13-g weight from a height of 30 cm to the exposed spinal cord at the T12-L1 vertebral level of the trained monkeys. All the monkeys showed significant impairments in every reflex activity and in walking behavior during the early part of the postoperative period. In subsequent periods, the animals displayed mild alterations in certain reflex responses, such as grasping, extension withdrawal, and placing reflexes, which persisted through a 1-year follow-up. The contused animals traversed locomotor runways--narrow beam, incline plane, and grid runways--with more steps and few errors, as evaluated with the CBS system. Eventually, the behavioral performance of all spinal-contused monkeys recovered to near-preoperative level by the fifth postoperative month. The findings of this study reveal the recovery time course of various reflex components and bipedal locomotor behavior of spinal-contused macaques on runways for a postoperative period of up to 1 year. Our spinal cord research in primates is advantageous in understanding the characteristics of hind limb functions only, which possibly mimic the human motor behavior. This study may be also useful in detecting the beneficial effect of various donor tissue-neuroprotective drugs on the repair of impaired functions in a bipedal primate model of spinal injury.

[The influence of non-invasive electrical stimulation of the spinal cord on the locomotor function of patients presenting with movement disorders of central genesis].

PubMed

Balykin, M V; Yakupov, R N; Mashin, V V; Kotova, E Yu; Balykin, Yu M; Gerasimenko, Yu P

The objective of the present study was to evaluate the influence of non-invasive (transcutaneous) electrical spinal cord stimulation on the locomotor function of the patients suffering from movement disorders. The study involved 10 patients of both sexes at the age from 32 to 70 years (including 40% of men and 60% of women) presenting with the compromised locomotor function of varying severity associated with the disturbances of cerebral blood circulation caused either by an injury to the brain and spinal cord or by stroke. The transcutaneous electrical spinal cord stimulation was applied using different frequency regimes with the placement of the electrodes in the projection onto the region of TXI-TXII vertebrae. The active factors were bipolar electrical stimuli 0.5 ms in duration; the current strength was chosen for each patient on an individual basis taking into consideration its threshold level. Electromyograms and evoked motor responses of selected muscles, viz. m. rectus femoris, m.biceps femoris, m. tibialis anterior, and m.gastrocnemius were recorded with the use of the 'Neuro-MVP-8 eight-channel electromyography' ('Neurosoft', Russia). The data obtained give evidence that the stimulation of the spinal cord with a frequency of 1 Hz induces reflectory responses with monosynaptic and polysynaptic components in the muscles of the lower extremities, with the thresholds of these responses being significantly higher in the patients presenting with serious neurological problems. Stimulation with the frequencies of 5 and 30 Hz caused in the patients with paresis the involuntary movement of the legs the characteristics of which were similar to those of the locomotor movements. It has been demonstrated that the application of transcutaneous electrical spinal cord stimulation leads to increased excitability of the lumbar spinal neural structures of the patients. The study has shown the possibility of regulation of the locomotor functions in the patients presenting with movement disorders of central genesis by means of non-invasive electrical stimulation of the spinal cord.

Assessment of abdominal muscle function in individuals with motor-complete spinal cord injury above T6 in response to transcranial magnetic stimulation.

PubMed

Bjerkefors, Anna; Squair, Jordan W; Chua, Romeo; Lam, Tania; Chen, Zhen; Carpenter, Mark G

2015-02-01

To use transcranial magnetic stimulation and electromyography to assess the potential for preserved function in the abdominal muscles in individuals classified with motor-complete spinal cord injury above T6. Five individuals with spinal cord injury (C5-T3) and 5 able-bodied individuals. Transcranial magnetic stimulation was delivered over the abdominal region of primary motor cortex during resting and sub-maximal (or attempted) contractions. Surface electromyography was used to record motor-evoked potentials as well as maximal voluntary (or attempted) contractions in the abdominal muscles and the diaphragm. Responses to transcranial magnetic stimulation in the abdominal muscles occurred in all spinal cord injury subjects. Latencies of muscle response onsets were similar in both groups; however, peak-to-peak amplitudes were smaller in the spinal cord injury group. During maximal voluntary (or attempted) contractions all spinal cord injury subjects were able to elicit electromyography activity above resting levels in more than one abdominal muscle across tasks. Individuals with motor-complete spinal cord injury above T6 were able to activate abdominal muscles in response to transcranial magnetic stimulation and during maximal voluntary (or attempted) contractions. The activation was induced directly through corticospinal pathways, and not indirectly by stretch reflex activations of the diaphragm. Transcranial magnetic stimulation and electromyography measurements provide a useful method to assess motor preservation of abdominal muscles in persons with spinal cord injury.

Characterizing Dysphagia and Swallowing Intervention in the Traumatic Spinal Injury Population

PubMed Central

Valenzano, Teresa J.; Waito, Ashley A.; Steele, Catriona M.

2016-01-01

Dysphagia is reported to be a common secondary complication for individuals with traumatic spinal injuries. Different etiologies of traumatic spinal injuries may lead to different profiles of swallowing impairment. We conducted a systematic review to determine the characteristics of dysphagia after traumatic spinal injury and to describe interventions currently used to improve swallowing function in this population. A comprehensive multi-engine literature search identified 137 articles of which 5 were judged to be relevant. These underwent review for study quality, rating for level of evidence, and data extraction. The literature describing dysphagia after traumatic spinal injury was comprised predominantly of low level evidence and single case reports. Aspiration, pharyngeal residue, and decreased/absent hyolaryngeal elevation were found to be common characteristics of dysphagia in this population. The most commonly used swallowing interventions included tube feeding, compensatory swallowing strategies, and steroids/antibiotics. Improvement in swallowing function following swallowing intervention was reported in all studies, however there was no control for spontaneous recovery. The results demonstrate a need for high-quality research to profile the pathophysiology of dysphagia after traumatic spinal injury and controlled studies to demonstrate the efficacy of swallowing interventions in this population. PMID:27412004

A Review of Dysphagia Presentation and Intervention Following Traumatic Spinal Injury: An Understudied Population.

PubMed

Valenzano, Teresa J; Waito, Ashley A; Steele, Catriona M

2016-10-01

Dysphagia is reported to be a common secondary complication for individuals with traumatic spinal injuries. Different etiologies of traumatic spinal injuries may lead to different profiles of swallowing impairment. We conducted a systematic review to determine the characteristics of dysphagia after traumatic spinal injury and to describe interventions currently used to improve swallowing function in this population. A comprehensive multiengine literature search identified 137 articles of which five were judged to be relevant. These underwent review for study quality, rating for level of evidence, and data extraction. The literature describing dysphagia after traumatic spinal injury was comprised predominantly of low-level evidence and single case reports. Aspiration, pharyngeal residue, and decreased/absent hyolaryngeal elevation were found to be common characteristics of dysphagia in this population. The most commonly used swallowing interventions included tube feeding, compensatory swallowing strategies, and steroids/antibiotics. Improvement in swallowing function following swallowing intervention was reported in all studies; however, there was no control for spontaneous recovery. The results demonstrate a need for high-quality research to profile the pathophysiology of dysphagia after traumatic spinal injury and controlled studies to demonstrate the efficacy of swallowing interventions in this population.

Prevalence and Causes of Paralysis—United States, 2013

PubMed Central

Armour, Brian S.; Courtney-Long, Elizabeth A.; Fox, Michael H.; Fredine, Heidi; Cahill, Anthony

2017-01-01

Objectives To estimate the prevalence and causes of functional paralysis in the United States. Methods We used the 2013 US Paralysis Prevalence & Health Disparities Survey to estimate the prevalence of paralysis, its causes, associated sociodemographic characteristics, and health effects among this population. Results Nearly 5.4 million persons live with paralysis. Most persons with paralysis were younger than 65 years (72.1%), female (51.7%), White (71.4%), high school graduates (64.8%), married or living with a partner (47.4%), and unable to work (41.8%). Stroke is the leading cause of paralysis, affecting 33.7% of the population with paralysis, followed by spinal cord injury (27.3%), multiple sclerosis (18.6%), and cerebral palsy (8.3%). Conclusions According to the functional definition, persons living with paralysis represent a large segment of the US population, and two thirds of them are between ages 18 and 64 years. Targeted health promotion that uses inclusion strategies to account for functional limitations related to paralysis can be undertaken in partnership with state and local health departments. PMID:27552260

AN IL-1 RECEPTOR ANTAGONIST BLOCKS A MORPHINE-INDUCED ATTENUATION OF LOCOMOTOR RECOVERY AFTER SPINAL CORD INJURY

PubMed Central

Hook, Michelle A.; Washburn, Stephanie N.; Moreno, Georgina; Woller, Sarah A.; Puga, Denise; Lee, Kuan H.; Grau, James W.

2010-01-01

Morphine is one of the most commonly prescribed medications for the treatment of chronic pain after a spinal cord injury (SCI). Despite widespread use, however, little is known about the secondary consequences of morphine use after SCI. Unfortunately, our previous studies show that administration of a single dose of morphine, in the acute phase of a moderate spinal contusion injury, significantly attenuates locomotor function, reduces weight gain, and produces symptoms of paradoxical pain (Hook et al., 2009). The current study focused on the cellular mechanisms that mediate these effects. Based on data from other models, we hypothesized that pro-inflammatory cytokines might play a role in the morphine-induced attenuation of function. Experiment 1 confirmed that systemic morphine (20 mg/kg) administered one day after a contusion injury significantly increased expression levels of spinal IL-1β 24 hrs later. Experiment 2 extended these findings, demonstrating that a single dose of morphine (90 µg, i.t.) applied directly onto the spinal cord increased expression levels of spinal IL-1β at both 30 min and 24 hrs after administration. Experiment 3 showed that administration of an interleukin-1 receptor antagonist (IL-1ra, i.t.) prior to intrathecal morphine (90 µg), blocked the adverse effects of morphine on locomotor recovery. Further, pre-treatment with 3 µg IL-1ra prevented the increased expression of at-level neuropathic pain symptoms that was observed 28 days later in the group treated with morphine-alone. However, the IL-1ra also had adverse effects that were independent of morphine. Treatment with the IL-1ra alone undermined recovery of locomotor function, potentiated weight loss and significantly increased tissue loss at the injury site. Overall, these data suggest that morphine disrupts a critical balance in concentrations of pro-inflammatory cytokines in the spinal cord, and this undermines recovery of function. PMID:20974246

Reproducibility of resting state spinal cord networks in healthy volunteers at 7 Tesla.

PubMed

Barry, Robert L; Rogers, Baxter P; Conrad, Benjamin N; Smith, Seth A; Gore, John C

2016-06-01

We recently reported our findings of resting state functional connectivity in the human spinal cord: in a cohort of healthy volunteers we observed robust functional connectivity between left and right ventral (motor) horns and between left and right dorsal (sensory) horns (Barry et al., 2014). Building upon these results, we now quantify the within-subject reproducibility of bilateral motor and sensory networks (intraclass correlation coefficient=0.54-0.56) and explore the impact of including frequencies up to 0.13Hz. Our results suggest that frequencies above 0.08Hz may enhance the detectability of these resting state networks, which would be beneficial for practical studies of spinal cord functional connectivity. Copyright © 2016 Elsevier Inc. All rights reserved.

Vertebral Column Resection for Kyphoscoliosis in a Patient with Ehlers-Danlos Syndrome: An Intraoperative Neurophysiological Monitoring Alert.

PubMed

Jahangiri, Faisal R; Al Eissa, Sami; Sayegh, Samir; Al Helal, Fahad; Al-Sharif, Shomoukh A; Annaim, Monerah M; Muhammad, Sheryar; Aziz, Tanweer

2016-08-31

A 16-year-old male patient with Ehler-Danlos syndrome (EDS) and a back deformity since birth presented with severe kyphoscoliosis. The patient was neurologically intact but had respiratory and cardiac insufficiencies. A two-stage vertebral column resection (VCR) at T9-T10 with multiple level fusion with multimodality intraoperative neurophysiological monitoring (IONM) was planned.  During the first stage, pedicle screws were placed at multiple spinal levels above and below the VCR level. Upper and lower somatosensory evoked potentials (SSEP), transcranial electrical motor evoked potentials (TCeMEP), and electromyography were monitored continuously and showed no significant changes. The second stage was performed one week later. Baseline SSEP and TCeMEP responses were present in all extremities. The surgeon was informed of a sudden 70% amplitude drop in TCeMEP in the lower limbs with stable SSEP after ligating one of the left nerves/vessels fully stretching the spinal cord. The surgeon removed the ligation, and an improvement in motor responses followed. Surgery proceeded with the highest levels of caution. Later, there was a sudden loss of TCeMEP and SSEP in the lower limbs bilaterally. The correction was released, mean arterial pressure was increased, and intravenous dexamethasone was administered. The surgical correction was aborted, and the decision was made to close the site. Lower SSEP and TCeMEP responses remained absent until closing, while upper SSEP and TCeMEP responses remained stable. A wake-up test was done after closing. The patient moved his upper limbs but was unable to move his lower limbs bilaterally. The patient was sent for a magnetic resonance imaging scan while intubated and then sent to the intensive care unit. At 24 hours and 36 hours post-operation, the patient had no sensory and motor function below the T8 level. Forty-eight hours post-operation, the patient started to feel sensory stimuli at the T10 level. At one week post-operation, the patient regained sphincter functions, and at four weeks postoperatively, the patient's hip flexors started to recover. VCR in patients with EDS has a very high risk of damaging the spinal cord due to the fragile vasculature of the spinal cord. Real-time IONM is useful in the early identification of spinal cord injury in cases of this nature.

Vertebral Column Resection for Kyphoscoliosis in a Patient with Ehlers-Danlos Syndrome: An Intraoperative Neurophysiological Monitoring Alert

PubMed Central

Al Eissa, Sami; Sayegh, Samir; Al Helal, Fahad; Al-Sharif, Shomoukh A; Annaim, Monerah M; Muhammad, Sheryar; Aziz, Tanweer

2016-01-01

A 16-year-old male patient with Ehler-Danlos syndrome (EDS) and a back deformity since birth presented with severe kyphoscoliosis. The patient was neurologically intact but had respiratory and cardiac insufficiencies. A two-stage vertebral column resection (VCR) at T9-T10 with multiple level fusion with multimodality intraoperative neurophysiological monitoring (IONM) was planned.  During the first stage, pedicle screws were placed at multiple spinal levels above and below the VCR level. Upper and lower somatosensory evoked potentials (SSEP), transcranial electrical motor evoked potentials (TCeMEP), and electromyography were monitored continuously and showed no significant changes. The second stage was performed one week later. Baseline SSEP and TCeMEP responses were present in all extremities. The surgeon was informed of a sudden 70% amplitude drop in TCeMEP in the lower limbs with stable SSEP after ligating one of the left nerves/vessels fully stretching the spinal cord. The surgeon removed the ligation, and an improvement in motor responses followed. Surgery proceeded with the highest levels of caution. Later, there was a sudden loss of TCeMEP and SSEP in the lower limbs bilaterally. The correction was released, mean arterial pressure was increased, and intravenous dexamethasone was administered. The surgical correction was aborted, and the decision was made to close the site. Lower SSEP and TCeMEP responses remained absent until closing, while upper SSEP and TCeMEP responses remained stable. A wake-up test was done after closing. The patient moved his upper limbs but was unable to move his lower limbs bilaterally. The patient was sent for a magnetic resonance imaging scan while intubated and then sent to the intensive care unit. At 24 hours and 36 hours post-operation, the patient had no sensory and motor function below the T8 level. Forty-eight hours post-operation, the patient started to feel sensory stimuli at the T10 level. At one week post-operation, the patient regained sphincter functions, and at four weeks postoperatively, the patient’s hip flexors started to recover. VCR in patients with EDS has a very high risk of damaging the spinal cord due to the fragile vasculature of the spinal cord. Real-time IONM is useful in the early identification of spinal cord injury in cases of this nature.  PMID:27766191

Engaging Cervical Spinal Cord Networks to Reenable Volitional Control of Hand Function in Tetraplegic Patients.

PubMed

Lu, Daniel C; Edgerton, V Reggie; Modaber, Morteza; AuYong, Nicholas; Morikawa, Erika; Zdunowski, Sharon; Sarino, Melanie E; Sarrafzadeh, Majid; Nuwer, Marc R; Roy, Roland R; Gerasimenko, Yury

2016-11-01

Paralysis of the upper limbs from spinal cord injury results in an enormous loss of independence in an individual's daily life. Meaningful improvement in hand function is rare after 1 year of tetraparesis. Therapeutic developments that result in even modest gains in hand volitional function will significantly affect the quality of life for patients afflicted with high cervical injury. The ability to neuromodulate the lumbosacral spinal circuitry via epidural stimulation in regaining postural function and volitional control of the legs has been recently shown. A key question is whether a similar neuromodulatory strategy can be used to improve volitional motor control of the upper limbs, that is, performance of motor tasks considered to be less "automatic" than posture and locomotion. In this study, the effects of cervical epidural stimulation on hand function are characterized in subjects with chronic cervical cord injury. Herein we show that epidural stimulation can be applied to the chronic injured human cervical spinal cord to promote volitional hand function. Two subjects implanted with a cervical epidural electrode array demonstrated improved hand strength (approximately 3-fold) and volitional hand control in the presence of epidural stimulation. The present data are sufficient to suggest that hand motor function in individuals with chronic tetraplegia can be improved with cervical cord neuromodulation and thus should be comprehensively explored as a possible clinical intervention. © The Author(s) 2016.

The Spinal Cord Injury- Functional Index: Item Banks to Measure Physical Functioning of Individuals with Spinal Cord Injury

PubMed Central

Tulsky, David S.; Jette, Alan; Kisala, Pamela A.; Kalpakjian, Claire; Dijkers, Marcel P.; Whiteneck, Gale; Ni, Pengsheng; Kirshblum, Steven; Charlifue, Susan; Heinemann, Allen W.; Forchheimer, Martin; Slavin, Mary; Houlihan, Bethlyn; Tate, Denise; Dyson-Hudson, Trevor; Fyffe, Denise; Williams, Steve; Zanca, Jeanne

2012-01-01

Objective To develop a comprehensive set of patient reported items to assess multiple aspects of physical functioning relevant to the lives of people with spinal cord injury (SCI) and to evaluate the underlying structure of physical functioning. Design Cross-sectional Setting Inpatient and community Participants Item pools of physical functioning were developed, refined and field tested in a large sample of 855 individuals with traumatic spinal cord injury stratified by diagnosis, severity, and time since injury Interventions None Main Outcome Measure SCI-FI measurement system Results Confirmatory factor analysis (CFA) indicated that a 5-factor model, including basic mobility, ambulation, wheelchair mobility, self care, and fine motor, had the best model fit and was most closely aligned conceptually with feedback received from individuals with SCI and SCI clinicians. When just the items making up basic mobility were tested in CFA, the fit statistics indicate strong support for a unidimensional model. Similar results were demonstrated for each of the other four factors indicating unidimensional models. Conclusions Though unidimensional or 2-factor (mobility and upper extremity) models of physical functioning make up outcomes measures in the general population, the underlying structure of physical function in SCI is more complex. A 5-factor solution allows for comprehensive assessment of key domain areas of physical functioning. These results informed the structure and development of the SCI-FI measurement system of physical functioning. PMID:22609299

Effect of motor unit recruitment on functional vasodilatation in hamster retractor muscle

PubMed Central

Van Teeffelen, Jurgen W G E; Segal, Steven S

2000-01-01

The effect of motor unit recruitment on functional vasodilatation was investigated in hamster retractor muscle. Recruitment (i.e. peak tension) was controlled with voltage applied to the spinal accessory nerve (high = maximum tension; intermediate = ∼50% maximum; low = ∼25% maximum). Vasodilatory responses (diameter × time integral, DTI) to rhythmic contractions (1 per 2 s for 65 s) were evaluated in first, second and third orderarterioles and in feed arteries. Reciprocal changes in duty cycle (range, 2·5–25 %) effectively maintained the total active tension (tension × time integral, TTI) constant across recruitment levels. With constant TTI and stimulation frequency (40 Hz), DTI in all vessels increased with motor unit recruitment. DTI increased from distal arterioles up through proximal feed arteries. To determine whether the effect of recruitment on DTI was due to increased peak tension, the latter was controlled with stimulation frequency (15, 20 and 40 Hz) during maximum (high) recruitment. With constant TTI, DTI then decreased as peak tension increased. To explore the interaction between recruitment and duty cycle on DTI, each recruitment level was applied at 2.5, 10 and 20 % duty cycle (at 40 Hz). For a given increase in TTI, recruitment had a greater effect on DTI than did duty cycle. Functional vasodilatation in response to rhythmic contractions is facilitated by motor unit recruitment. Thus, vasodilatory responses are determined not only by the total tension produced, but also by the number of active motor units. PMID:10747197

Function after spinal treatment, exercise and rehabilitation (FASTER): improving the functional outcome of spinal surgery

PubMed Central

2010-01-01

Background The life-time incidence of low back pain is high and diagnoses of spinal stenosis and disc prolapse are increasing. Consequently, there is a steady rise in surgical interventions for these conditions. Current evidence suggests that while the success of surgery is incomplete, it is superior to conservative interventions. A recent survey indicates that there are large differences in the type and intensity of rehabilitation, if any, provided after spinal surgery as well as in the restrictions and advice given to patients in the post-operative period. This trial will test the hypothesis that functional outcome following two common spinal operations can be improved by a programme of post-operative rehabilitation that combines professional support and advice with graded active exercise and/or an educational booklet based on evidence-based messages and advice. Methods/Design The study design is a multi-centre, factorial, randomised controlled trial with patients stratified by surgeon and operative procedure. The trial will compare the effectiveness and cost-effectiveness of a rehabilitation programme and an education booklet for the postoperative management of patients undergoing discectomy or lateral nerve root decompression, each compared with "usual care"using a 2 × 2 factorial design. The trial will create 4 sub-groups; rehabilitation-only, booklet-only, rehabilitation-plus-booklet, and usual care only. The trial aims to recruit 344 patients, which equates to 86 patients in each of the four sub-groups. All patients will be assessed for functional ability (through the Oswestry Disability Index - a disease specific functional questionnaire), pain (using visual analogue scales), and satisfaction pre-operatively and then at 6 weeks, 3, 6 and 9 months and 1 year post-operatively. This will be complemented by a formal analysis of cost-effectiveness. Discussion This trial will determine whether the outcome of spinal surgery can be enhanced by either a post-operative rehabilitation programme or an evidence-based advice booklet or a combination of the two and as such will contribute to our knowledge on how to manage spinal surgery patients in the post-operative period. Trial Registration Current controlled trials ISRCTN46782945 UK CRN ID: 2670 PMID:20102625

Function after spinal treatment, exercise and rehabilitation (FASTER): improving the functional outcome of spinal surgery.

PubMed

McGregor, A H; Doré, C J; Morris, T P; Morris, S; Jamrozik, K

2010-01-26

The life-time incidence of low back pain is high and diagnoses of spinal stenosis and disc prolapse are increasing. Consequently, there is a steady rise in surgical interventions for these conditions. Current evidence suggests that while the success of surgery is incomplete, it is superior to conservative interventions. A recent survey indicates that there are large differences in the type and intensity of rehabilitation, if any, provided after spinal surgery as well as in the restrictions and advice given to patients in the post-operative period. This trial will test the hypothesis that functional outcome following two common spinal operations can be improved by a programme of post-operative rehabilitation that combines professional support and advice with graded active exercise and/or an educational booklet based on evidence-based messages and advice. The study design is a multi-centre, factorial, randomised controlled trial with patients stratified by surgeon and operative procedure. The trial will compare the effectiveness and cost-effectiveness of a rehabilitation programme and an education booklet for the postoperative management of patients undergoing discectomy or lateral nerve root decompression, each compared with "usual care"using a 2 x 2 factorial design. The trial will create 4 sub-groups; rehabilitation-only, booklet-only, rehabilitation-plus-booklet, and usual care only. The trial aims to recruit 344 patients, which equates to 86 patients in each of the four sub-groups. All patients will be assessed for functional ability (through the Oswestry Disability Index - a disease specific functional questionnaire), pain (using visual analogue scales), and satisfaction pre-operatively and then at 6 weeks, 3, 6 and 9 months and 1 year post-operatively. This will be complemented by a formal analysis of cost-effectiveness. This trial will determine whether the outcome of spinal surgery can be enhanced by either a post-operative rehabilitation programme or an evidence-based advice booklet or a combination of the two and as such will contribute to our knowledge on how to manage spinal surgery patients in the post-operative period.

Ergonomics intervention on an alternative design of a spinal board.

PubMed

Zadry, Hilma Raimona; Susanti, Lusi; Rahmayanti, Dina

2017-09-01

A spinal board is the evacuation tool of first aid to help the injured spinal cord. The existing spinal board has several weaknesses, both in terms of user comfort and the effectiveness and efficiency of the evacuation process. This study designs an ergonomic spinal board using the quality function deployment approach. A preliminary survey was conducted through direct observation and interviews with volunteers from the Indonesian Red Cross. Data gathered were translated into a questionnaire and answered by 47 participants in West Sumatra. The results indicate that the selection of materials, the application of strap systems as well as the addition of features are very important in designing an ergonomic spinal board. The data were used in designing an ergonomic spinal board. The use of anthropometric data ensures that this product can accommodate safety and comfort when immobilized, as well as the flexibility and speed of the rescue evacuation process.

Recurrent ‘universal tumour’ of the spinal cord

PubMed Central

O'Grady, John; Kaliaperumal, Chandrasekaran; O'Sullivan, Michael

2012-01-01

Lipoma is popularly known as the ‘universal tumour’ because of its ubiquitous presence anywhere in the body. This is the first documented case of recurrent thoracic spinal cord intramedullary lipoma in a 44-year-old man, with a background of spinal dysraphism, which recurred 15 years after initial surgery. He was followed up every 2 years and currently presented with an 8-month history of progressive weakness in his lower limbs. An MRI of the spine confirmed recurrence of lipoma. He underwent redo laminectomy and partial resection and spinal cord decompression with duroplasty. Lipoma, although a low-grade tumour, can cause significant neurological deficits because of its location. Surgical exploration and removal of lipoma is recommended. However, to preserve the functionality of the spinal cord, one may resort to partial resection and aim for spinal cord decompression. The literature on spinal cord lipoma is reviewed and the aetiopathogenesis of this rare occurrence is described. PMID:22675149

Effects of cathodal trans-spinal direct current stimulation on lower urinary tract function in normal and spinal cord injury mice with overactive bladder

NASA Astrophysics Data System (ADS)

Ahmed, Zaghloul

2017-10-01

Objective. Lower urinary tract (LUT) dysfunction is a monumental problem affecting quality of life following neurotrauma, such as spinal cord injury (SCI). Proper function of the bladder and its associated structures depends on coordinated activity of the neuronal circuitry in the spinal cord and brain. Disconnection between the spinal and brain centers controlling the LUT causes fundamental changes in the mechanisms involved in the micturition and storage reflexes. We investigated the effects of cathodal trans-spinal direct current stimulation (c-tsDCS) of the lumbosacral spine on bladder and external urinary sphincter (EUS) functions. Approach. We used cystometry and electromyography (EMG), in mice with and without SCI. Main results. c-tsDCS caused initiation of the micturition reflex in urethane-anesthetized normal mice with depressed micturition reflexes. This effect was associated with normalized EUS-EMG activity. Moreover, in urethane-anesthetized normal mice with expressed micturition reflexes, c-tsDCS increased the firing frequency, amplitude, and duration of EUS-EMG activity. These effects were associated with increased maximum intravesical pressure (P max) and intercontraction interval (ICI). In conscious normal animals, c-tsDCS caused significant increases in P max, ICI, threshold pressure (P thres), baseline pressure (P base), and number and amplitude of non-voiding contractions (NVCnumb and P im, respectively). In conscious mice with severe contusive SCI and overactive bladder, c-tsDCS increased P max, ICI, and P thres, but decreased P base, NVCnumb, and P im. c-tsDCS reduced the detrusor-overactivity/cystometry ratio, which is a measure of bladder overactivity associated with renal deterioration. Significance. These results indicate that c-tsDCS induces robust modulation of the lumbosacral spinal-cord circuitry that controls the LUT.

Effect of DSPE-PEG on compound action potential, injury potential and ion concentration following compression in ex vivo spinal cord.

PubMed

Wang, Aihua; Huo, Xiaolin; Zhang, Guanghao; Wang, Xiaochen; Zhang, Cheng; Wu, Changzhe; Rong, Wei; Xu, Jing; Song, Tao

2016-05-04

It has been shown that polyethylene glycol (PEG) can reseal membrane disruption on the spinal cord, but only high concentrations of PEG have been shown to have this effect. Therefore, the effect of PEG is somewhat limited, and it is necessary to investigate a new approach to repair spinal cord injury. This study assesses the ability of 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly (ethylene glycol)) 2000] (DSPE-PEG) to recover physiological function and attenuate the injury-induced influx of extracellular ions in ex vivo spinal cord injury. Isolated spinal cords were subjected to compression injury and treated with PEG or DSPE-PEG immediately after injury. The compound action potential (CAP) was recorded before and after injury to assess the functional recovery. Furthermore, injury potential, the difference in gap potentials before and after compression, and the concentration of intracellular ions were used to evaluate the effect of DSPE-PEG on reducing ion influx. Data showed that the injury potential and ion concentration of the untreated, PEG and DSPE-PEG group, without significant difference among them, are remarkably higher than those of the intact group. Moreover, the CAP recovery of the DSPE-PEG and PEG treated spinal cords was significantly greater than that of the untreated spinal cords. The level of CAP recovery in the DSPE-PEG and PEG treated groups was the same, but the concentration of DSPE-PEG used was much lower than the concentration of PEG. These results suggest that instant application of DSPE-PEG could effectively repair functional disturbance in SCI at a much lower concentration than PEG. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Assessing Forelimb Function after Unilateral Cervical SCI using Novel Tasks: Limb Step-alternation, Postural Instability and Pasta Handling

PubMed Central

Schallert, Timothy; Schmidt, Christine E.

2013-01-01

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority of the spinal cord injuries in humans occur at the cervical levels. Therefore, developing cervical injury models and developing relevant and sensitive behavioral tests is of great importance. Here we describe the use of a newly developed forelimb step-alternation test after cervical spinal cord injury in rats. In addition, we describe two behavioral tests that have not been used after spinal cord injury: a postural instability test (PIT), and a pasta-handling test. All three behavioral tests are highly sensitive to injury and are easy to use. Therefore, we feel that these behavioral tests can be instrumental in investigating therapeutic strategies after cSCI. PMID:24084700

Assessing forelimb function after unilateral cervical SCI using novel tasks: limb step-alternation, postural instability and pasta handling.

PubMed

Khaing, Zin Z; Geissler, Sydney A; Schallert, Timothy; Schmidt, Christine E

2013-09-16

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority of the spinal cord injuries in humans occur at the cervical levels. Therefore, developing cervical injury models and developing relevant and sensitive behavioral tests is of great importance. Here we describe the use of a newly developed forelimb step-alternation test after cervical spinal cord injury in rats. In addition, we describe two behavioral tests that have not been used after spinal cord injury: a postural instability test (PIT), and a pasta-handling test. All three behavioral tests are highly sensitive to injury and are easy to use. Therefore, we feel that these behavioral tests can be instrumental in investigating therapeutic strategies after cSCI.

Neural tube closure depends on expression of Grainyhead-like 3 in multiple tissues.

PubMed

De Castro, Sandra C P; Hirst, Caroline S; Savery, Dawn; Rolo, Ana; Lickert, Heiko; Andersen, Bogi; Copp, Andrew J; Greene, Nicholas D E

2018-03-15

Failure of neural tube closure leads to neural tube defects (NTDs), common congenital abnormalities in humans. Among the genes whose loss of function causes NTDs in mice, Grainyhead-like3 (Grhl3) is essential for spinal neural tube closure, with null mutants exhibiting fully penetrant spina bifida. During spinal neurulation Grhl3 is initially expressed in the surface (non-neural) ectoderm, subsequently in the neuroepithelial component of the neural folds and at the node-streak border, and finally in the hindgut endoderm. Here, we show that endoderm-specific knockout of Grhl3 causes late-arising spinal NTDs, preceded by increased ventral curvature of the caudal region which was shown previously to suppress closure of the spinal neural folds. This finding supports the hypothesis that diminished Grhl3 expression in the hindgut is the cause of spinal NTDs in the curly tail, carrying a hypomorphic Grhl3 allele. Complete loss of Grhl3 function produces a more severe phenotype in which closure fails earlier in neurulation, before the stage of onset of expression in the hindgut of wild-type embryos. This implicates additional tissues and NTD mechanisms in Grhl3 null embryos. Conditional knockout of Grhl3 in the neural plate and node-streak border has minimal effect on closure, suggesting that abnormal function of surface ectoderm, where Grhl3 transcripts are first detected, is primarily responsible for early failure of spinal neurulation in Grhl3 null embryos. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

A cellular spinal cord scaffold seeded with rat adipose-derived stem cells facilitates functional recovery via enhancing axon regeneration in spinal cord injured rats

PubMed Central

Yin, Hong; Jiang, Tao; Deng, Xi; Yu, Miao; Xing, Hui; Ren, Xianjun

2018-01-01

Spinal cord injury (SCI), usually resulting in severe sensory and motor deficits, is a major public health concern. Adipose-derived stem cells (ADSCs), one type of adult stem cell, are free from ethical restriction, easily isolated and enriched. Therefore, ADSCs may provide a feasible cell source for cell-based therapies in treatment of SCI. The present study successfully isolated rat ADSCs (rADSCs) from Sprague-Dawley male rats and co-cultured them with acellular spinal cord scaffolds (ASCs). Then, a rat spinal cord hemisection model was built and rats were randomly divided into 3 groups: SCI only, ASC only, and ASC + ADSCs. Furthermore, behavioral tests were conducted to evaluate functional recovery. Hematoxylin & Eosin staining and immunofluorence were carried out to assess histopathological remodeling. In addition, biotinylated dextran amines anterograde tracing was employed to visualize axon regeneration. The data demonstrated that harvested cells, which were positive for cell surface antigen cluster of differentiation (CD) 29, CD44 and CD90 and negative for CD4, detected by flow cytometry analysis, held the potential to differentiate into osteocytes and adipocytes. Rats that received transplantation of ASCs seeded with rADSCs benefited greatly in functional recovery through facilitation of histopathological rehabilitation, axon regeneration and reduction of reactive gliosis. rADSCs co-cultured with ASCs may survive and integrate into the host spinal cord on day 14 post-SCI. PMID:29257299

Mechanisms of motor recovery after subtotal spinal cord injury: insights from the study of mice carrying a mutation (WldS) that delays cellular responses to injury.

PubMed

Zhang, Z; Guth, L; Steward, O

1998-01-01

Partial lesions of the mammalian spinal cord result in an immediate motor impairment that recovers gradually over time; however, the cellular mechanisms responsible for the transient nature of this paralysis have not been defined. A unique opportunity to identify those injury-induced cellular responses that mediate the recovery of function has arisen from the discovery of a unique mutant strain of mice in which the onset of Wallerian degeneration is dramatically delayed. In this strain of mice (designated WldS for Wallerian degeneration, slow), many of the cellular responses to spinal cord injury are also delayed. We have used this experimental animal model to evaluate possible causal relationships between these delayed cellular responses and the onset of functional recovery. For this purpose, we have compared the time course of locomotor recovery in C57BL/6 (control) mice and in WldS (mutant) mice by hemisecting the spinal cord at T8 and evaluating locomotor function at daily postoperative intervals. The time course of locomotor recovery (as determined by the Tarlov open-field walking procedure) was substantially delayed in mice carrying the WldS mutation: C57BL/6 control mice began to stand and walk within 6 days (mean Tarlov score of 4), whereas mutant mice did not exhibit comparable locomotor function until 16 days postoperatively. (a) The rapid return of locomotor function in the C57BL/6 mice suggests that the recovery resulted from processes of functional plasticity rather than from regeneration or collateral sprouting of nerve fibers. (b) The marked delay in the return of locomotor function in WldS mice indicates that the processes of neuroplasticity are induced by degenerative changes in the damaged neurons. (c) These strains of mice can be effectively used in future studies to elucidate the specific biochemical and physiological alterations responsible for inducing functional plasticity and restoring locomotor function after spinal cord injury.

The Controversy Surrounding Bone Morphogenetic Proteins in the Spine: A Review of Current Research

PubMed Central

Hustedt, Joshua W.; Blizzard, Daniel J.

2014-01-01

Bone morphogenetic proteins have been in use in spinal surgery since 2002. These proteins are members of the TGF-beta superfamily and guide mesenchymal stem cells to differentiate into osteoblasts to form bone in targeted tissues. Since the first commercial BMP became available in 2002, a host of research has supported BMPs and they have been rapidly incorporated in spinal surgeries in the United States. However, recent controversy has arisen surrounding the ethical conduct of the research supporting the use of BMPs. Yale University Open Data Access (YODA) recently teamed up with Medtronic to offer a meta-analysis of the effectiveness of BMPs in spinal surgery. This review focuses on the history of BMPs and examines the YODA research to guide spine surgeons in their use of BMP in spinal surgery. PMID:25506287

The Effectiveness and Safety of Exoskeletons as Assistive and Rehabilitation Devices in the Treatment of Neurologic Gait Disorders in Patients with Spinal Cord Injury: A Systematic Review

PubMed Central

Fisahn, Christian; Aach, Mirko; Jansen, Oliver; Moisi, Marc; Mayadev, Angeli; Pagarigan, Krystle T.; Dettori, Joseph R.; Schildhauer, Thomas A.

2016-01-01

Study Design Systematic review. Clinical Questions (1) When used as an assistive device, do wearable exoskeletons improve lower extremity function or gait compared with knee-ankle-foot orthoses (KAFOs) in patients with complete or incomplete spinal cord injury? (2) When used as a rehabilitation device, do wearable exoskeletons improve lower extremity function or gait compared with other rehabilitation strategies in patients with complete or incomplete spinal cord injury? (3) When used as an assistive or rehabilitation device, are wearable exoskeletons safe compared with KAFO for assistance or other rehabilitation strategies for rehabilitation in patients with complete or incomplete spinal cord injury? Methods PubMed, Cochrane, and Embase databases and reference lists of key articles were searched from database inception to May 2, 2016, to identify studies evaluating the effectiveness of wearable exoskeletons used as assistive or rehabilitative devices in patients with incomplete or complete spinal cord injury. Results No comparison studies were found evaluating exoskeletons as an assistive device. Nine comparison studies (11 publications) evaluated the use of exoskeletons as a rehabilitative device. The 10-meter walk test velocity and Spinal Cord Independence Measure scores showed no difference in change from baseline among patients undergoing exoskeleton training compared with various comparator therapies. The remaining primary outcome measures of 6-minute walk test distance and Walking Index for Spinal Cord Injury I and II and Functional Independence Measure–Locomotor scores showed mixed results, with some studies indicating no difference in change from baseline between exoskeleton training and comparator therapies, some indicating benefit of exoskeleton over comparator therapies, and some indicating benefit of comparator therapies over exoskeleton. Conclusion There is no data to compare locomotion assistance with exoskeleton versus conventional KAFOs. There is no consistent benefit from rehabilitation using an exoskeleton versus a variety of conventional methods in patients with chronic spinal cord injury. Trials comparing later-generation exoskeletons are needed. PMID:27853668

Differential fMRI Activation Patterns to Noxious Heat and Tactile Stimuli in the Primate Spinal Cord

PubMed Central

Yang, Pai-Feng; Wang, Feng

2015-01-01

Mesoscale local functional organizations of the primate spinal cord are largely unknown. Using high-resolution fMRI at 9.4 T, we identified distinct interhorn and intersegment fMRI activation patterns to tactile versus nociceptive heat stimulation of digits in lightly anesthetized monkeys. Within a spinal segment, 8 Hz vibrotactile stimuli elicited predominantly fMRI activations in the middle part of ipsilateral dorsal horn (iDH), along with significantly weaker activations in ipsilateral (iVH) and contralateral (cVH) ventral horns. In contrast, nociceptive heat stimuli evoked widespread strong activations in the superficial part of iDH, as well as in iVH and contralateral dorsal (cDH) horns. As controls, only weak signal fluctuations were detected in the white matter. The iDH responded most strongly to both tactile and heat stimuli, whereas the cVH and cDH responded selectively to tactile versus nociceptive heat, respectively. Across spinal segments, iDH activations were detected in three consecutive segments in both tactile and heat conditions. Heat responses, however, were more extensive along the cord, with strong activations in iVH and cDH in two consecutive segments. Subsequent subunit B of cholera toxin tracer histology confirmed that the spinal segments showing fMRI activations indeed received afferent inputs from the stimulated digits. Comparisons of the fMRI signal time courses in early somatosensory area 3b and iDH revealed very similar hemodynamic stimulus–response functions. In summary, we identified with fMRI distinct segmental networks for the processing of tactile and nociceptive heat stimuli in the cervical spinal cord of nonhuman primates. SIGNIFICANCE STATEMENT This is the first fMRI demonstration of distinct intrasegmental and intersegmental nociceptive heat and touch processing circuits in the spinal cord of nonhuman primates. This study provides novel insights into the local functional organizations of the primate spinal cord for pain and touch, information that will be valuable for designing and optimizing therapeutic interventions for chronic pain management. PMID:26203144

Reliability and validity of simplified Chinese version of Swiss Spinal Stenosis Questionnaire for patients with degenerative lumbar spinal stenosis.

PubMed

Yi, Honglei; Wei, Xianzhao; Zhang, Wei; Chen, Ziqiang; Wang, Xinhui; Ji, Xinran; Zhu, Xiaodong; Wang, Fei; Xu, Ximing; Li, Zhikun; Fan, Jianping; Wang, Chuanfeng; Chen, Kai; Zhang, Guoyou; Zhao, Yinchuan; Li, Ming

2014-05-01

This was a prospective clinical validation study. To evaluate the reliability and validity of the adapted simplified Chinese version of Swiss Spinal Stenosis (SC-SSS) Questionnaire. The SSS Questionnaire is a reliable and valid instrument to assess the perception of function and pain for patients with degenerative lumbar spinal stenosis. However, there is no culturally adapted SSS Questionnaire for use in mainland China. This was a prospective clinical validation study. The adaption was conducted according to International Quality of Life Assessment Project guidelines. To examine the psychometric properties of the adapted SC-SSS Questionnaire, a sample of 105 patients with lumbar spinal stenosis were included. Thirty-two patients were randomly selected to evaluate the test-retest reliability. Reliability assessment of the SC-SSS Questionnaire was determined by calculating Cronbach α and intraclass coefficient values. Concurrent validity was assessed by correlating SC-SSS Questionnaire scores with relevant domains of the 36-Item Short Form Health Survey. Cronbach α of the symptom severity scale, physical function scale, patients, and satisfaction scale of SC-SSS Questionnaire are 0.89, 0.86, 0.91, respectively, which revealed very good internal consistency. The test-retest reproducibility was found to be excellent with the intraclass correlation coefficient of 0.93, 0.91, and 0.95. In terms of concurrent validity, SC-SSS Questionnaire had good correlation with physical functioning and bodily pain of 36-Item Short Form Health Survey (r = 0.663, 0.653) and low correlation with mental health (r = 0.289). The physical function scale had good correlation with physical functioning of 36-Item Short Form Health Survey (r = 0.637), whereas the rest had moderate correlation. The satisfaction scale score was highly correlated with the change in the symptom severity (r = 0.71) and physical function (r = 0.68) scale score. The SC-SSS Questionnaire showed satisfactory reliability and validity in the evaluation of functionality in patients with lumbar spinal stenosis who are experiencing neurogenic claudication. It is simple and easy to use and can be recommended in clinical and research practice in mainland China. 3.

Specialisation of spinal services: consequences for cervical trauma management in the district hospital

PubMed Central

Rethnam, Ulfin; Cordell-Smith, James; Sinha, Amit

2007-01-01

Background Specialisation in spinal services has lead to a low threshold for referral of cervical spine injuries from district general hospitals. We aim to assess the capability of a district general hospital in providing the halo vest device and the expertise available in applying the device for unstable cervical spine injuries prior to transfer to a referral centre. Methods The study was a postal questionnaire survey of trauma consultants at district general hospitals without on-site spinal units in the United Kingdom. Seventy institutions were selected randomly from an electronic NHS directory. We posed seven questions on the local availability, expertise and training with halo vest application, and transferral policies in patients with spinal trauma. Results The response rate was 51/70 (73%). Nineteen of the hospitals (37%) did not stock the halo vest device. Also, one third of the participants (18/51, 35%, 95% confidence interval 22 – 50%) were not confident in application of the halo vest device and resorted to transfer of patients to referral centres without halo immobilization. Conclusion The lack of equipment and expertise to apply the halo vest device for unstable cervical spine injuries is highlighted in this study. Training of all trauma surgeons in the application of the halo device would overcome this deficiency. PMID:18271985

Multimodal intraoperative monitoring: an overview and proposal of methodology based on 1,017 cases

PubMed Central

Eggspuehler, Andreas; Muller, Alfred; Dvorak, Jiri

2007-01-01

To describe different currently available tests of multimodal intraoperative monitoring (MIOM) used in spine and spinal cord surgery indicating the technical parameters, application and interpretation as an easy understanding systematic overview to help implementation of MIOM and improve communication between neurophysiologists and spine surgeons. This article aims to give an overview and proposal of the different MIOM-techniques as used daily in spine and spinal cord surgery at our institution. Intensive research in neurophysiology over the past decades has lead to a profound understanding of the spinal cord, nerve functions and their intraoperative functional evaluation in anaesthetised patients. At present, spine surgeons and neurophysiologist are faced with 1,883 publications in PubMed on spinal cord monitoring. The value and the limitations of single monitoring methods are well documented. The diagnostic power of the multimodal approach in a larger study population in spine surgery, as measured with sensitivity and specificity, is dealt with elsewhere in this supplement (Sutter et al. in Eur Spine J Suppl, 2007). This paper aims to give a detailed description of the different modalities used in this study. Description of monitoring techniques of the descending and ascending spinal cord and nerve root pathways by motor evoked potentials of the spinal cord and muscles elicited after transcranial electrical motor cortex, spinal cord, cauda equina and nerve root stimulation, continuous EMG, sensory cortical and spinal evoked potentials, as well as direct spinal cord evoked potentials applied on 1,017 patients. The method of MIOM, continuously adapted according to the site, stage of surgery and potential danger to nerve tissues, proved to be applicable with online results, reliable and furthermore teachable. PMID:17653777

Episodic swimming in the larval zebrafish is generated by a spatially distributed spinal network with modular functional organization

PubMed Central

Wiggin, Timothy D.; Anderson, Tatiana M.; Eian, John; Peck, Jack H.

2012-01-01

Despite the diverse methods vertebrates use for locomotion, there is evidence that components of the locomotor central pattern generator (CPG) are conserved across species. When zebrafish begin swimming early in development, they perform short episodes of activity separated by periods of inactivity. Within these episodes, the trunk flexes with side-to-side alternation and the traveling body wave progresses rostrocaudally. To characterize the distribution of the swimming CPG along the rostrocaudal axis, we performed transections of the larval zebrafish spinal cord and induced fictive swimming using N-methyl-d-aspartate (NMDA). In both intact and spinalized larvae, bursting is found throughout the rostrocaudal extent of the spinal cord, and the properties of fictive swimming observed were dependent on the concentration of NMDA. We isolated series of contiguous spinal segments by performing multiple spinal transections on the same larvae. Although series from all regions of the spinal cord have the capacity to produce bursts, the capacity to produce organized episodes of fictive swimming has a rostral bias: in the rostral spinal cord, only 12 contiguous body segments are necessary, whereas 23 contiguous body segments are necessary in the caudal spinal cord. Shorter series of segments were often active but produced either continuous rhythmic bursting or sporadic, nonrhythmic bursting. Both episodic and continuous bursting alternated between the left and right sides of the body and showed rostrocaudal progression, demonstrating the functional dissociation of the circuits responsible for episodic structure and fine burst timing. These findings parallel results in mammalian locomotion, and we propose a hierarchical model of the larval zebrafish swimming CPG. PMID:22572943

Return-to-work intentions during spinal cord injury rehabilitation: an audit of employment outcomes.

PubMed

Kennedy, P; Hasson, L

2016-02-01

Single-centre, retrospective cohort study. To analyse the return-to-work intentions during spinal cord injury (SCI) rehabilitation. Tertiary care, spinal cord injury rehabilitation unit, National Spinal Injuries Centre, Stoke Mandeville Hospital, Ayelsbury, UK. Employment outcomes were obtained from the Needs Assessment Checklist (NAC), for all patients admitted to the unit between February 2008 and October 2014. NAC1 is completed within 4 weeks post-mobilisation and NAC2 upon the patient moving to the pre-discharge ward. Data from 362 participants were analysed for return-to-work intentions, by gender, age and injury severity. Seventy-six percent of the sample population was employed at the time of their injury. At NAC1, 22.4% of individuals had made plans to return to work, whereas 44.2% had not; at NAC2, 34.3% had made plans to return to work and 31.2% had not. This difference was found to be statistically significant. There were significant differences in return-to-work intentions by injury severity at NAC1 but not NAC2, and by age group at NAC2 but not NAC1. Less than half of those employed at the time of their injury had made plans to return to work before their discharge from the unit. The low proportion of individuals with SCI returning to work--just one in three--is concerning in view of the lost health and psychosocial benefits, and requires greater prominence during rehabilitation. Future research into effective employment interventions to improve employment outcomes in this population is required.

Diffusion Tensor Imaging as a Predictor of Locomotor Function after Experimental Spinal Cord Injury and Recovery

PubMed Central

Kelley, Brian J.; Harel, Noam Y.; Kim, Chang-Yeon; Papademetris, Xenophon; Coman, Daniel; Wang, Xingxing; Hasan, Omar; Kaufman, Adam; Globinsky, Ronen; Staib, Lawrence H.; Cafferty, William B.J.; Hyder, Fahmeed

2014-01-01

Abstract Traumatic spinal cord injury (SCI) causes long-term disability with limited functional recovery linked to the extent of axonal connectivity. Quantitative diffusion tensor imaging (DTI) of axonal integrity has been suggested as a potential biomarker for prognostic and therapeutic evaluation after trauma, but its correlation with functional outcomes has not been clearly defined. To examine this application, female Sprague-Dawley rats underwent midthoracic laminectomy followed by traumatic spinal cord contusion of differing severities or laminectomy without contusion. Locomotor scores and hindlimb kinematic data were collected for 4 weeks post-injury. Ex vivo DTI was then performed to assess axonal integrity using tractography and fractional anisotropy (FA), a numerical measure of relative white matter integrity, at the injury epicenter and at specific intervals rostral and caudal to the injury site. Immunohistochemistry for tissue sparing was also performed. Statistical correlation between imaging data and functional performance was assessed as the primary outcome. All injured animals showed some recovery of locomotor function, while hindlimb kinematics revealed graded deficits consistent with injury severity. Standard T2 magnetic resonance sequences illustrated conventional spinal cord morphology adjacent to contusions while corresponding FA maps indicated graded white matter pathology within these adjacent regions. Positive correlations between locomotor (Basso, Beattie, and Bresnahan score and gait kinematics) and imaging (FA values) parameters were also observed within these adjacent regions, most strongly within caudal segments beyond the lesion. Evaluation of axonal injury by DTI provides a mechanism for functional recovery assessment in a rodent SCI model. These findings suggest that focused DTI analysis of caudal spinal cord should be studied in human cases in relationship to motor outcome to augment outcome biomarkers for clinical cases. PMID:24779685

The Correlation Between Recordable MEPs and Motor Function During Spinal Surgery for Resection of Thoracic Spinal Cord Tumor.

PubMed

Guo, LanJun; Li, Yan; Han, Ruquan; Gelb, Adrian W

2018-01-01

Motor evoked potentials (MEPs) are commonly used during surgery for spinal cord tumor resection. However, it can be difficult to record reliable MEPs from the muscles of the lower extremities during surgery in patients with preoperative weakness due to spinal cord compression. In this study, motor function of patients' lower extremities and their association with intraoperative MEP recording were compared. Patients undergoing thoracic spinal cord tumor resection were studied. Patients' motor function was checked immediately before the surgical procedure. MEP responses were recorded from the tibialis anterior and foot muscles, and the hand muscles were used as control. Electrical current with train of eight pulses, 200 to 500 V was delivered through 2 corkscrews placed at C3' and C4' sites. Anesthesia was maintained by total intravenous anesthesia using a combination of propofol and remifentanil after induction with intravenous propofol, remifentanil, and rocuronium. Rocuronium was not repeated. Bispectral Index was maintained between 40 to 50. From 178 lower limbs of 89 patients, myogenic MEPs could be recorded from 100% (105/105) of the patients with 5 of 5 motor strength in lower extremity; 90% (36/40) from the patients with 4/5 motor strength; only 25% (5/20) with 3/5; and 12.5% (1/8) with 2/5 motor strength; none (0/5) were able to be recorded if the motor strength was 1/5. The ability to record myogenic MEPs is closely associated with the patient's motor function. They are difficult to obtain if motor function is 3/5 motor strength in the lower extremity. They are almost impossible to record if motor function is worse than 3/5.

Changes in Sexual Activity in Male Patients Surgically Treated for Kyphosis due to Ankylosing Spondylitis.

PubMed

Yao, Ziming; Du, Jianwei; Wang, Zheng; Zheng, Guoquan; Zhang, Xuesong; Cui, Geng; Wang, Yan

2016-09-01

A retrospective study. The aim of this study was to assess the changes in sexual activities in male patients surgically treated for ankylosing spondylitis (AS)-induced kyphosis and the correlation between these changes and spinal sagittal realignment. Sexual function may be affected by AS. However, little is known about the effect of spinal surgery on the sexual activity of patients with AS-induced kyphosis. Data of 45 male patients who had been surgically treated for AS-induced kyphosis were retrospectively reviewed. Changes in sexual activity were evaluated by the international index of erectile function (IIEF), frequency of sexual activity, and time point at which sexual activity began postoperatively. We compared the above-mentioned parameters before and 24 months postoperatively and analyzed the correlation of the changes in the IIEF with the changes in radiological characteristics. Each domain of the IIEF and the total IIEF were increased postoperatively. Improved sexual function was correlated with changes in spinal sagittal characteristics, among which lumbar lordosis (LL) and the chin-brow vertical angle (CBVA) were the most significant causes (P < 0.05). Most patients (71.1%) resumed their sexual activity 5 to 12 weeks after surgery. At the 24-month follow-up, the frequency of patients' sexual activity was higher than that before surgery (P < 0.05). Surgical correction of spinal deformity may improve sexual function and increase the frequency of sexual activity in men with AS. Spinal sagittal realignment and pelvic rotation may be correlated with improvement of sexual function. 4.

Hindlimb Immobilization in a Wheelchair Alters Functional Recovery Following Contusive Spinal Cord Injury in the Adult Rat

PubMed Central

Caudle, Krista L.; Brown, Edward H.; Shum-Siu, Alice; Burke, Darlene A.; Magnuson, Trystan S. G.; Voor, Michael J.; Magnuson, David S. K.

2015-01-01

Background Locomotor training of rats with thoracic contusion spinal cord injuries can induce task-specific changes in stepping but rarely results in improved overground locomotion, possibly due to a ceiling effect. Thus, the authors hypothesize that incompletely injured rats maximally retrain themselves while moving about in their cages over the first few weeks postinjury. Objective To test the hypothesis using hindlimb immobilization after mild thoracic contusion spinal cord injury in adult female rats. A passive stretch protocol was included as an independent treatment. Methods Wheelchairs were used to hold the hindlimbs stationary in an extended position leaving the forelimbs free. The wheelchairs were used for 15 to 18 hours per day, 5 days per week for 8 weeks, beginning at 4 days postinjury. A 20-minute passive hindlimb stretch therapy was applied to half of the animals. Results Hindlimb locomotor function of the wheelchair group was not different from controls at 1 week postinjury but declined significantly over the next 4 weeks. Passive stretch had no influence on wheelchair animals but limited functional recovery of normally housed animals, preventing them from regaining forelimb–hindlimb coordination. Following 8 weeks of wheelchair immobilization and stretch therapy, only the wheelchair group displayed an improvement in function when returned to normal housing but retained significant deficits in stepping and coordination out to 16 weeks. Conclusion Hindlimb immobilization and passive stretch may hinder or conceal the normal course of functional recovery of spinal cord injured rats. These observations have implications for the management of acute clinical spinal cord injuries. PMID:21697451

Body-Machine Interfaces after Spinal Cord Injury: Rehabilitation and Brain Plasticity.

PubMed

Seáñez-González, Ismael; Pierella, Camilla; Farshchiansadegh, Ali; Thorp, Elias B; Wang, Xue; Parrish, Todd; Mussa-Ivaldi, Ferdinando A

2016-12-19

The purpose of this study was to identify rehabilitative effects and changes in white matter microstructure in people with high-level spinal cord injury following bilateral upper-extremity motor skill training. Five subjects with high-level (C5-C6) spinal cord injury (SCI) performed five visuo-spatial motor training tasks over 12 sessions (2-3 sessions per week). Subjects controlled a two-dimensional cursor with bilateral simultaneous movements of the shoulders using a non-invasive inertial measurement unit-based body-machine interface. Subjects' upper-body ability was evaluated before the start, in the middle and a day after the completion of training. MR imaging data were acquired before the start and within two days of the completion of training. Subjects learned to use upper-body movements that survived the injury to control the body-machine interface and improved their performance with practice. Motor training increased Manual Muscle Test scores and the isometric force of subjects' shoulders and upper arms. Moreover, motor training increased fractional anisotropy (FA) values in the cingulum of the left hemisphere by 6.02% on average, indicating localized white matter microstructure changes induced by activity-dependent modulation of axon diameter, myelin thickness or axon number. This body-machine interface may serve as a platform to develop a new generation of assistive-rehabilitative devices that promote the use of, and that re-strengthen, the motor and sensory functions that survived the injury.

Transspinal direct current stimulation modulates migration and proliferation of adult newly born spinal cells in mice.

PubMed

Samaddar, Sreyashi; Vazquez, Kizzy; Ponkia, Dipen; Toruno, Pedro; Sahbani, Karim; Begum, Sultana; Abouelela, Ahmed; Mekhael, Wagdy; Ahmed, Zaghloul

2017-02-01

Direct current electrical fields have been shown to be a major factor in the regulation of cell proliferation, differentiation, migration, and survival, as well as in the maturation of dividing cells during development. During adulthood, spinal cord cells are continuously produced in both animals and humans, and they hold great potential for neural restoration following spinal cord injury. While the effects of direct current electrical fields on adult-born spinal cells cultured ex vivo have recently been reported, the effects of direct current electrical fields on adult-born spinal cells in vivo have not been characterized. Here, we provide convincing findings that a therapeutic form of transspinal direct current stimulation (tsDCS) affects the migration and proliferation of adult-born spinal cells in mice. Specifically, cathodal tsDCS attracted the adult-born spinal cells, while anodal tsDCS repulsed them. In addition, both tsDCS polarities caused a significant increase in cell number. Regarding the potential mechanisms involved, both cathodal and anodal tsDCS caused significant increases in expression of brain-derived neurotrophic factor, while expression of nerve growth factor increased and decreased, respectively. In the spinal cord, both anodal and cathodal tsDCS increased blood flow. Since blood flow and angiogenesis are associated with the proliferation of neural stem cells, increased blood flow may represent a major factor in the modulation of newly born spinal cells by tsDCS. Consequently, we propose that the method and novel findings presented in the current study have the potential to facilitate cellular, molecular, and/or bioengineering strategies to repair injured spinal cords. NEW & NOTEWORTHY Our results indicate that transspinal direct current stimulation (tsDCS) affects the migratory pattern and proliferation of adult newly born spinal cells, a cell population which has been implicated in learning and memory. In addition, our results suggest a potential mechanism of action regarding the functional effects of applying direct current. Thus tsDCS may represent a novel method by which to manipulate the migration and cell number of adult newly born cells and restore functions following brain or spinal cord injury. Copyright © 2017 the American Physiological Society.

Functional Characterization of Lamina X Neurons in ex-Vivo Spinal Cord Preparation.

PubMed

Krotov, Volodymyr; Tokhtamysh, Anastasia; Kopach, Olga; Dromaretsky, Andrew; Sheremet, Yevhenii; Belan, Pavel; Voitenko, Nana

2017-01-01

Functional properties of lamina X neurons in the spinal cord remain unknown despite the established role of this area for somatosensory integration, visceral nociception, autonomic regulation and motoneuron output modulation. Investigations of neuronal functioning in the lamina X have been hampered by technical challenges. Here we introduce an ex-vivo spinal cord preparation with both dorsal and ventral roots still attached for functional studies of the lamina X neurons and their connectivity using an oblique LED illumination for resolved visualization of lamina X neurons in a thick tissue. With the elaborated approach, we demonstrate electrophysiological characteristics of lamina X neurons by their membrane properties, firing pattern discharge and fiber innervation (either afferent or efferent). The tissue preparation has been also probed using Ca 2+ imaging with fluorescent Ca 2+ dyes (membrane-impermeable or -permeable) to demonstrate the depolarization-induced changes in intracellular calcium concentration in lamina X neurons. Finally, we performed visualization of subpopulations of lamina X neurons stained by retrograde labeling with aminostilbamidine dye to identify sympathetic preganglionic and projection neurons in the lamina X. Thus, the elaborated approach provides a reliable tool for investigation of functional properties and connectivity in specific neuronal subpopulations, boosting research of lamina X of the spinal cord.

The Extract of Roots of Sophora flavescens Enhances the Recovery of Motor Function by Axonal Growth in Mice with a Spinal Cord Injury.

PubMed

Tanabe, Norio; Kuboyama, Tomoharu; Kazuma, Kohei; Konno, Katsuhiro; Tohda, Chihiro

2015-01-01

Although axonal extension to reconstruct spinal tracts should be effective for restoring function after spinal cord injury (SCI), chondroitin sulfate proteoglycan (CSPG) levels increase at spinal cord lesion sites, and inhibit axonal regrowth. In this study, we found that the water extract of roots of Sophora flavescens extended the axons of mouse cortical neurons, even on a CSPG-coated surface. Consecutive oral administrations of S. flavescens extract to SCI mice for 31 days increased the density of 5-HT-positive axons at the lesion site and improved the motor function. Further, the active constituents in the S. flavescens extract were identified. The water and alkaloid fractions of the S. flavescens extract each exhibited axonal extension activity in vitro. LC/MS analysis revealed that these fractions mainly contain matrine and/or oxymatrine, which are well-known major compounds in S. flavescens. Matrine and oxymatrine promoted axonal extension on the CSPG-coated surface. This study is the first to demonstrate that S. flavescens extract, matrine, and oxymatrine enhance axonal growth in vitro, even on a CSPG-coated surface, and that S. flavescens extract improves motor function and increases axonal density in SCI mice.

Mediators of disability and hope for people with spinal cord injury.

PubMed

Phillips, Brian N; Smedema, Susan M; Fleming, Allison R; Sung, Connie; Allen, Michael G

2016-08-01

To test potential strength-based mediators of functional disability and hope in adults with spinal cord injury. Two hundred and forty-two participants with spinal cord injury were recruited for this study. The mean age of participants was 44.6 years (standard deviation = 13.2), and 66.1% were men. Participants completed a survey containing a demographic questionnaire, as well as measures of functional disability, hope, self-esteem, proactive coping, perceived social support and disability acceptance. Mediation analysis was conducted using a bootstrap test for multiple mediators. Proactive coping, self-esteem and perceived social support significantly mediated the relationship between functional disability and hope, while disability acceptance did not. The combination of mediators resulted in functional disability no longer being a significant predictor of hope. The strength-based constructs of proactive coping, self-esteem and social support appear effective in predicting hope regardless of severity of spinal cord injury. Functional disability was no longer predictive of hope after controlling for these strength-based constructs. Disability acceptance did not significantly add to the mediation model. These results provide further evidence for strength-based interventions in rehabilitation. Implications for Rehabilitation Strength-based constructs of proactive coping, self-esteem and social support are important factors for addressing hope following spinal cord injury, regardless of level of severity. Rehabilitation services providers should focus efforts on supporting clients in the accurate appraisal of predictable stressors and then generate means for addressing them as a form of proactive coping. Rehabilitation services providers must be cautious when addressing self-esteem to focus on perceived competence and learning processes rather than self-esteem directly or through the accomplishment of goals that may not be achieved. Knowing that social supports are related to hope post-spinal cord injury, it is important for rehabilitation services providers to recognize potential social supports early in the rehabilitation process and involve those social supports in the rehabilitation process when possible.

Neuromodulation of the lumbar spinal locomotor circuit.

PubMed

AuYong, Nicholas; Lu, Daniel C

2014-01-01

The lumbar spinal cord contains the necessary circuitry to independently drive locomotor behaviors. This function is retained following spinal cord injury (SCI) and is amenable to rehabilitation. Although the effectiveness of task-specific training and pharmacologic modulation has been repeatedly demonstrated in animal studies, results from human studies are less striking. Recently, lumbar epidural stimulation (EDS) along with locomotor training was shown to restore weight-bearing function and lower-extremity voluntary control in a chronic, motor-complete human SCI subject. Related animal studies incorporating EDS as part of the therapeutic regiment are also encouraging. EDS is emerging as a promising neuromodulatory tool for SCI. Copyright © 2014 Elsevier Inc. All rights reserved.

SU-E-T-397: Evaluation of Planned Dose Distributions by Monte Carlo (0.5%) and Ray Tracing Algorithm for the Spinal Tumors with CyberKnife

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cho, H; Brindle, J; Hepel, J

2015-06-15

Purpose: To analyze and evaluate dose distribution between Ray Tracing (RT) and Monte Carlo (MC) algorithms of 0.5% uncertainty on a critical structure of spinal cord and gross target volume and planning target volume. Methods: Twenty four spinal tumor patients were treated with stereotactic body radiotherapy (SBRT) by CyberKnife in 2013 and 2014. The MC algorithm with 0.5% of uncertainty is used to recalculate the dose distribution for the treatment plan of the patients using the same beams, beam directions, and monitor units (MUs). Results: The prescription doses are uniformly larger for MC plans than RT except one case. Upmore » to a factor of 1.19 for 0.25cc threshold volume and 1.14 for 1.2cc threshold volume of dose differences are observed for the spinal cord. Conclusion: The MC recalculated dose distributions are larger than the original MC calculations for the spinal tumor cases. Based on the accuracy of the MC calculations, more radiation dose might be delivered to the tumor targets and spinal cords with the increase prescription dose.« less

Spinal cord injuries in Australian footballers.

PubMed

2003-07-01

Acute spinal cord injury is a serious concern in football, particularly the rugby codes. This Australia-wide study covers the years 1986-1996 and data are compared with those from a previous identical study for 1960-1985. A retrospective review of 80 players with a documented acute spinal cord injury admitted to the six spinal cord injury units in Australia. Personal interview was carried out in 85% of the participants to determine the injury circumstances and the level of compensation. The severity of the neurological deficit and the functional recovery were determined (Frankel grade). The annual incidence of injuries for all codes combined did not change over the study period, but there was some decrease in rugby union and an increase in rugby league. In particular there was a significant decline in the incidence of adult rugby union injuries (P = 0.048). Scrum injuries in union have decreased subsequent to law changes in 1985, particularly in schoolboys, although ruck and maul injuries are increasing; 39% of scrum injuries occurred in players not in their regular position. Tackles were the most common cause of injury in league, with two-on-one tackles accounting for nearly half of these. Schoolboy injuries tended to mirror those in adults, but with a lower incidence. Over half of the players remain wheelchair-dependent, and 10% returned to near-normality. Six players (7.5%) died as a result of their injuries. The rugby codes must be made safer by appropriate preventative strategies and law changes. In particular, attention is necessary for tackle injuries in rugby league and players out of regular position in scrummage. Compensation for injured players is grossly inadequate. There is an urgent need to establish a national registry to analyse these injuries prospectively.

The temporal profile of the reaction of microglia, astrocytes, and macrophages in the delayed onset paraplegia after transient spinal cord ischemia in rabbits.

PubMed

Matsumoto, Satoshi; Matsumoto, Mishiya; Yamashita, Atsuo; Ohtake, Kazunobu; Ishida, Kazuyoshi; Morimoto, Yasuhiro; Sakabe, Takefumi

2003-06-01

In the present study, we sought to elucidate the temporal profile of the reaction of microglia, astrocytes, and macrophages in the progression of delayed onset motor dysfunction after spinal cord ischemia (15 min) in rabbits. At 2, 4, 8, 12, 24, and 48 h after reperfusion (9 animals in each), hind limb motor function was assessed, and the lumbar spinal cord was histologically examined. Delayed motor dysfunction was observed in most animals at 48 h after ischemia, which could be predicted by a poor recovery of segmental spinal cord evoked potentials at 15 min of reperfusion. In the gray matter of the lumbar spinal cord, both microglia and astrocytes were activated early (2 h) after reperfusion. Microglia were diffusely activated and engulfed motor neurons irrespective of the recovery of segmental spinal cord evoked potentials. In contrast, early astrocytic activation was confined to the area where neurons started to show degeneration. Macrophages were first detected at 8 h after reperfusion and mainly surrounded the infarction area later. Although the precise roles of the activation of microglia, astrocytes, and macrophages are to be further determined, the results indicate that understanding functional changes of astrocytes may be important in the mechanism of delayed onset motor dysfunction including paraplegia. Microglia and macrophages play a role in removing tissue debris after transient spinal cord ischemia. Disturbance of astrocytic defense mechanism, breakdown of the blood-spinal cord barrier, or both seemed to be involved in the development of delayed motor dysfunction.

International bowel function basic spinal cord injury data set.

PubMed

Krogh, K; Perkash, I; Stiens, S A; Biering-Sørensen, F

2009-03-01

International expert working group. To develop an International Bowel Function Basic Spinal Cord Injury (SCI) Data Set presenting a standardized format for the collection and reporting of a minimal amount of information on bowel function in daily practice or in research. Working group consisting of members appointed by the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS). A draft prepared by the working group was reviewed by Executive Committee of the International SCI Standards and Data Sets, and later by ISCoS Scientific Committee and the ASIA Board. Relevant and interested scientific and professional (international) organizations and societies (approximately 40) were also invited to review the data set and it was posted on the ISCoS and ASIA websites for 3 months to allow comments and suggestions. The ISCoS Scientific Committee, Council and ASIA Board received the data set for final review and approval. The International Bowel Function Basic SCI Data Set includes the following 12 items: date of data collection, gastrointestinal or anal sphincter dysfunction unrelated to SCI, surgical procedures on the gastrointestinal tract, awareness of the need to defecate, defecation method and bowel care procedures, average time required for defecation, frequency of defecation, frequency of fecal incontinence, need to wear pad or plug, medication affecting bowel function/constipating agents, oral laxatives and perianal problems. An International Bowel Function Basic SCI Data Set has been developed.

Oral erlotinib, but not rapamycin, causes modest acceleration of bladder and hindlimb recovery from spinal cord injury in rats.

PubMed

Kjell, J; Pernold, K; Olson, L; Abrams, M B

2014-03-01

Erlotinib and Rapamycin are both in clinical use and experimental inhibition of their respective molecular targets, EGFR and mTORC1, has improved recovery from spinal cord injury. Our aim was to determine if daily Erlotinib or Rapamycin treatment started directly after spinal contusion injury in rats improves locomotion function or recovery of bladder function. Stockholm, Sweden. Rats were subjected to contusion injuries and treated during the acute phase with either Erlotinib or Rapamycin. Recovery of bladder function was monitored by measuring residual urine volume and hindlimb locomotion assessed by open-field observations using the BBB rating scale as well as by automated registration of gait parameters. Body weights were monitored. To determine whether Erlotinib and Rapamycin inhibit the same signaling pathway, a cell culture system and western blots were used. Erlotinib accelerated locomotor recovery and slightly improved bladder recovery; however, we found no long-term improvements of locomotor function. Rapamycin did neither improved locomotor function nor bladder recovery. In vitro studies confirmed that Erlotinib and Rapamycin both inhibit the EGFR-mTORC1 signaling pathway. We conclude that none of these two drug regimes improved long-term functional outcome in our current model of spinal cord injury. Nevertheless, oral treatment with Erlotinib may offer modest temporary advantages, whereas treatment with Rapamycin does not.

Panax ginseng Improves Functional Recovery after Contusive Spinal Cord Injury by Regulating the Inflammatory Response in Rats: An In Vivo Study

PubMed Central

Kim, Young Ock; Kim, Youngkyung; Lee, Koeun; Na, Sae Won; Hong, Seon Pyo; Valan Arasu, Mariadhas; Yoon, Young Wook; Kim, Junesun

2015-01-01

Spinal cord injury (SCI) results in permanent loss of motor function below the injured site. Neuroinflammatory reaction following SCI can aggravate neural injury and functional impairment. Ginseng is well known to possess anti-inflammatory effects. The present study investigated the neuroprotective effects of Panax ginseng C.A. Mayer (P. ginseng) after SCI. A spinal contusion was made at the T11-12 spinal cord in adult male Sprague-Dawley rats (n = 47) using the NYU impactor. Motor function was assessed using the Basso-Beattie-Bresnahan (BBB) score in P. ginseng (0.1, 0.5, 1, 3, and 5 mg/kg) or vehicle (saline) treated after SCI. We also assessed the protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) at the lesion site by western blot and then measured the cavity area using luxol fast blue/cresyl violet staining. P. ginseng treated group in SCI showed a significant improvement in locomotor function after the injury. The protein expression of COX-2 and iNOS at the lesion site and the cavity area were decreased following SCI by P. ginseng treatment. These results suggest that P. ginseng may improve the recovery of motor function after SCI which provides neuroprotection by alleviating posttraumatic inflammatory responses. PMID:26451158

Increases in human motoneuron excitability after cervical spinal cord injury depend on the level of injury.

PubMed

Thomas, Christine K; Häger, Charlotte K; Klein, Cliff S

2017-02-01

After human spinal cord injury (SCI), motoneuron recruitment and firing rate during voluntary and involuntary contractions may be altered by changes in motoneuron excitability. Our aim was to compare F waves in single thenar motor units paralyzed by cervical SCI to those in uninjured controls because at the single-unit level F waves primarily reflect the intrinsic properties of the motoneuron and its initial segment. With intraneural motor axon stimulation, F waves were evident in all 4 participants with C 4 -level SCI, absent in 8 with C 5 or C 6 injury, and present in 6 of 12 Uninjured participants (P < 0.001). The percentage of units that generated F waves differed across groups (C 4 : 30%, C 5 or C 6 : 0%, Uninjured: 16%; P < 0.001). Mean (±SD) proximal axon conduction velocity was slower after C 4 SCI [64 ± 4 m/s (n = 6 units), Uninjured: 73 ± 8 m/s (n = 7 units); P = 0.037]. Mean distal axon conduction velocity differed by group [C 4 : 40 ± 8 m/s (n = 20 units), C 5 or C 6 : 49 ± 9 m/s (n = 28), Uninjured: 60 ± 7 m/s (n = 45); P < 0.001]. Motor unit properties (EMG amplitude, twitch force) only differed after SCI (P ≤ 0.004), not by injury level. Motor units with F waves had distal conduction velocities, M-wave amplitudes, and twitch forces that spanned the respective group range, indicating that units with heterogeneous properties produced F waves. Recording unitary F waves has shown that thenar motoneurons closer to the SCI (C 5 or C 6 ) have reduced excitability whereas those further away (C 4 ) have increased excitability, which may exacerbate muscle spasms. This difference in motoneuron excitability may be related to the extent of membrane depolarization following SCI. Unitary F waves were common in paralyzed thenar muscles of people who had a chronic spinal cord injury (SCI) at the C 4 level compared with uninjured people, but F waves did not occur in people that had SCI at the C 5 or C 6 level. These results highlight that intrinsic motoneuron excitability depends, in part, on how close the motoneurons are to the site of the spinal injury, which could alter the generation and strength of voluntary and involuntary muscle contractions. Copyright © 2017 the American Physiological Society.

Clinical Response of 277 Patients with Spinal Cord Injury to Stem Cell Therapy in Iraq

PubMed Central

Hammadi, Abdulmajeed Alwan; Marino, Andolina; Farhan, Saad

2012-01-01

Background and Objectives: Spinal cord injury is a common neurological problem secondary to car accidents, war injuries and other causes, it may lead to varying degrees of neurological disablement, and apart from physiotherapy there is no available treatment to regain neurological function loss. Our aim is to find a new method using autologous hematopoietic stem cells to gain some of the neurologic functions lost after spinal cord injury. Methods and Results: 277 patients suffering from spinal cord injury were submitted to an intrathecally treatment with peripheral stem cells. The cells were harvested from the peripheral blood after a treatment with G-CSF and then concentrated to 4∼ 6 ml. 43% of the patients improved; ASIA score shifted from A to B in 88 and from A to C in 32. The best results were achieved in patients treated within one year from the injury. Conclusions: Since mesenchymal cells increase in the peripheral blood after G-CSF stimulation, a peripheral blood harvest seems easier and cheaper than mesenchymal cell cultivation prior to injection. It seems reasonable treatment for spinal cord injury. PMID:24298358

Opioid administration following spinal cord injury: Implications for pain and locomotor recovery

PubMed Central

Woller, Sarah A.; Hook, Michelle A.

2013-01-01

Approximately one-third of people with a spinal cord injury (SCI) will experience persistent neuropathic pain following injury. This pain negatively affects quality of life and is difficult to treat. Opioids are among the most effective drug treatments, and are commonly prescribed, but experimental evidence suggests that opioid treatment in the acute phase of injury can attenuate recovery of locomotor function. In fact, spinal cord injury and opioid administration share several common features (e.g. central sensitization, excitotoxicity, aberrant glial activation) that have been linked to impaired recovery of function, as well as the development of pain. Despite these effects, the interactions between opioid use and spinal cord injury have not been fully explored. A review of the literature, described here, suggests that caution is warranted when administering opioids after SCI. Opioid administration may synergistically contribute to the pathology of SCI to increase the development of pain, decrease locomotor recovery, and leave individuals at risk for infection. Considering these negative implications, it is important that guidelines are established for the use of opioids following spinal cord and other central nervous system injuries. PMID:23501709

The Effects of Ketorolac Injected via Patient Controlled Analgesia Postoperatively on Spinal Fusion

PubMed Central

Park, Si-Young; Moon, Seong-Hwan; Park, Moon-Soo; Oh, Kyung-Soo

2005-01-01

Lumbar spinal fusions have been performed for spinal stability, pain relief and improved function in spinal stenosis, scoliosis, spinal fractures, infectious conditions and other lumbar spinal problems. The success of lumbar spinal fusion depends on multifactors, such as types of bone graft materials, levels and numbers of fusion, spinal instrumentation, electrical stimulation, smoking and some drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs). From January 2000 to December 2001, 88 consecutive patients, who were diagnosed with spinal stenosis or spondylolisthesis, were retrospectively enrolled in this study. One surgeon performed all 88 posterolateral spinal fusions with instrumentation and autoiliac bone graft. The patients were divided into two groups. The first group (n=30) was infused with ketorolac and fentanyl intravenously via patient controlled analgesia (PCA) postoperatively and the second group (n=58) was infused only with fentanyl. The spinal fusion rates and clinical outcomes of the two groups were compared. The incidence of incomplete union or nonunion was much higher in the ketorolac group, and the relative risk was approximately 6 times higher than control group (odds ratio: 5.64). The clinical outcomes, which were checked at least 1 year after surgery, showed strong correlations with the spinal fusion status. The control group (93.1%) showed significantly better clinical results than the ketorolac group (77.6%). Smoking had no effect on the spinal fusion outcome in this study. Even though the use of ketorolac after spinal fusion can reduce the need for morphine, thereby decreasing morphine related complications, ketorolac used via PCA at the immediate postoperative state inhibits spinal fusion resulting in a poorer clinical outcome. Therefore, NSAIDs such as ketorolac, should be avoided after posterolateral spinal fusion. PMID:15861498

Progesterone Reduces Secondary Damage, Preserves White Matter, and Improves Locomotor Outcome after Spinal Cord Contusion

PubMed Central

Garcia-Ovejero, Daniel; González, Susana; Paniagua-Torija, Beatriz; Lima, Analía; Molina-Holgado, Eduardo; De Nicola, Alejandro F.

2014-01-01

Abstract Progesterone is an anti-inflammatory and promyelinating agent after spinal cord injury, but its effectiveness on functional recovery is still controversial. In the current study, we tested the effects of chronic progesterone administration on tissue preservation and functional recovery in a clinically relevant model of spinal cord lesion (thoracic contusion). Using magnetic resonance imaging, we observed that progesterone reduced both volume and rostrocaudal extension of the lesion at 60 days post-injury. In addition, progesterone increased the number of total mature oligodendrocytes, myelin basic protein immunoreactivity, and the number of axonal profiles at the epicenter of the lesion. Further, progesterone treatment significantly improved motor outcome as assessed using the Basso-Bresnahan-Beattie scale for locomotion and CatWalk gait analysis. These data suggest that progesterone could be considered a promising therapeutical candidate for spinal cord injury. PMID:24460450

Transplantation of oligodendrocyte precursors and sonic hedgehog results in improved function and white matter sparing in the spinal cords of adult rats after contusion.

PubMed

Bambakidis, Nicholas C; Miller, Robert H

2004-01-01

A substantial cause of neurological disability in spinal cord injury is oligodendrocyte death leading to demyelination and axonal degeneration. Rescuing oligodendrocytes and preserving myelin is expected to result in significant improvement in functional outcome after spinal cord injury. Although previous investigators have used cellular transplantation of xenografted pluripotent embryonic stem cells and observed improved functional outcome, these transplants have required steroid administration and only a minority of these cells develop into oligodendrocytes. The objective of the present study was to determine whether allografts of oligodendrocyte precursors transplanted into an area of incomplete spinal cord contusion would improve behavioral and electrophysiological measures of spinal cord function. Additional treatment incorporated the use of the glycoprotein molecule Sonic hedgehog (Shh), which has been shown to play a critical role in oligodendroglial development and induce proliferation of endogenous neural precursors after spinal cord injury. Laboratory study. Moderate spinal cord contusion injury was produced in 39 adult rats at T9-T10. Ten animals died during the course of the study. Nine rats served as contusion controls (Group 1). Six rats were treated with oligodendrocyte precursor transplantation 5 days after injury (Group 2). The transplanted cells were isolated from newborn rat pups using immunopanning techniques. Another eight rats received an injection of recombinant Shh along with the oligodendrocyte precursors (Group 3), while six more rats were treated with Shh alone (Group 4). Eight additional rats received only T9 laminectomies to serve as noninjured controls (Group 0). Animals were followed for 28 days. After an initial complete hindlimb paralysis, rats of all groups receiving a contusive injury recovered substantial function within 1 week. By 28 days, rats in Groups 2 and 3 scored 4.7 and 5.8 points better on the Basso, Beattie, Bresnahan (BBB) open field locomotor score than rats in group 1 (Groups 2 and 3=18.2 and 19.4 points, respectively, after 28 days vs. Group 1=13.6 points; p=.015). Rats in Group 4 scored no better than those in Group 1 (BBB=16.4). Motor evoked potential (MEP) recordings revealed a strong trend towards significant improvement in latency measurements in all treatment groups compared with controls at 28 days, although three animals in Group 1 and two animals in Group 3 were not recordable. Histological examination demonstrated significantly more spared white matter in the same groups that correlated with the improvements in BBB scores and MEP latencies. Immunohistochemical analysis showed the survival, proliferation and migration of the transplanted cells, as well as the induction of proliferating endogenous neural precursor cells in animals treated with Shh. These findings suggest that the transplantation of oligodendrocyte precursors may improve axonal conduction and spinal cord function in the injured spinal cord. The benefits seem more pronounced with the addition of Shh, and the addition of Shh alone results in the proliferation of an endogenous population of neural precursor cells.

Impact of spinal anaesthesia vs. general anaesthesia on peri-operative outcome in lumbar spine surgery: a systematic review and meta-analysis of randomised, controlled trials.

PubMed

Meng, T; Zhong, Z; Meng, L

2017-03-01

Lumbar spinal surgery is most commonly performed under general anaesthesia. However, spinal anaesthesia has also been used. We aimed to systematically review the comparative evidence. We only included randomised, controlled trials in this meta-analysis and calculated the risk ratio or standardised mean difference for haemodynamics, blood loss, surgical time, analgesic requirement, nausea and/or vomiting, and length of hospital stay. Eight studies with a total of 625 patients were included. These were considered to be at high risk of bias. Compared with general anaesthesia, the risk ratio (95% CI) with spinal anaesthesia for intra-operative hypertension was 0.31 (0.15-0.64), I 2 = 0% (p = 0.002); for intra-operative tachycardia 0.51 (0.30-0.84), I 2 = 0% (p = 0.009); for analgesic requirement in the postanaesthesia care unit 0.32 (0.24-0.43), I 2 = 0% (p < 0.0001); and for nausea/vomiting within 24 h postoperatively 0.29 (0.18-0.46), I 2 = 12% (p < 0.00001). The standardised mean difference (95% CI) for hospital stay was -1.15 (-1.98 to -0.31), I 2 = 89% (p = 0.007). There was no evidence of a difference in intra-operative hypotension and bradycardia, blood loss, surgical time, analgesic requirement within 24 h postoperatively, and nausea/vomiting in the postanaesthesia care unit. We conclude that spinal anaesthesia appears to offer advantages over general anaesthesia for lumbar spine surgery. © 2016 The Association of Anaesthetists of Great Britain and Ireland.

Functional status predicts acute care readmission in the traumatic spinal cord injury population.

PubMed

Huang, Donna; Slocum, Chloe; Silver, Julie K; Morgan, James W; Goldstein, Richard; Zafonte, Ross; Schneider, Jeffrey C

2018-03-29

Context/objective Acute care readmission has been identified as an important marker of healthcare quality. Most previous models assessing risk prediction of readmission incorporate variables for medical comorbidity. We hypothesized that functional status is a more robust predictor of readmission in the spinal cord injury population than medical comorbidities. Design Retrospective cross-sectional analysis. Setting Inpatient rehabilitation facilities, Uniform Data System for Medical Rehabilitation data from 2002 to 2012 Participants traumatic spinal cord injury patients. Outcome measures A logistic regression model for predicting acute care readmission based on demographic variables and functional status (Functional Model) was compared with models incorporating demographics, functional status, and medical comorbidities (Functional-Plus) or models including demographics and medical comorbidities (Demographic-Comorbidity). The primary outcomes were 3- and 30-day readmission, and the primary measure of model performance was the c-statistic. Results There were a total of 68,395 patients with 1,469 (2.15%) readmitted at 3 days and 7,081 (10.35%) readmitted at 30 days. The c-statistics for the Functional Model were 0.703 and 0.654 for 3 and 30 days. The Functional Model outperformed Demographic-Comorbidity models at 3 days (c-statistic difference: 0.066-0.096) and outperformed two of the three Demographic-Comorbidity models at 30 days (c-statistic difference: 0.029-0.056). The Functional-Plus models exhibited negligible improvements (0.002-0.010) in model performance compared to the Functional models. Conclusion Readmissions are used as a marker of hospital performance. Function-based readmission models in the spinal cord injury population outperform models incorporating medical comorbidities. Readmission risk models for this population would benefit from the inclusion of functional status.

Spinal analgesia and auditory functions: a comparison of two sizes of Quincke needle.

PubMed

Malhotra, S K; Iyer, B A; Gupta, A K; Raghunathan, M; Nakra, D

2007-01-01

Spinal anaesthesia may produce complications ranging from minor problems such as pain on injection, backache and urinary retention to more serious consequences such as post-dural puncture headache (PDPH), neurological complications like meningitis, cranial and peripheral nerve palsies and even cardiac arrest. Impaired auditory function is a relatively lesser-recognized complication of spinal analgesia. The objective of this study was to investigate the effects of spinal analgesia on vestibular dysfunction, using different sizes of the same type of spinal needle. The study included 30 ASA I patients who had received spinal analgesia for lower abdominal surgery. Pure tone audiometry was performed before surgery and on postoperative day 2. In addition, any patient with hearing impairment of >15 dB was scheduled to undergo electrocochleography. Hearing levels were measured from 250 Hz to 8 kHz. In group 1 (n=15), a 26gauge Quincke needle was used. In group 2 (n=15), a 23-gauge Quincke needle was used. Comparison of hearing thresholds showed a significant reduction in the hearing level (P<0.05) in 2 patients in group 2 but none in group 1. The use of a 23-gauge Quincke needle is associated with a greater reduction in the mean hearing level compared to a 26-gauge needle of the same type.

2-Decenoic acid ethyl ester, a derivative of unsaturated medium-chain fatty acids, facilitates functional recovery of locomotor activity after spinal cord injury.

PubMed

Hirakawa, A; Shimizu, K; Fukumitsu, H; Soumiya, H; Iinuma, M; Furukawa, S

2010-12-29

There is increasing evidence that omega-3 polyunsaturated fatty acids (PUFAs) have therapeutic potential in various animal models of neuronal injury. However, very few studies have examined the effect of medium-chain fatty acids (MCFAs) on neuronal injury. So in the present study we synthesized various MCFAs and their derivatives, and found that exposure to trans-2-decenoic acid ethyl ester (DAEE) markedly activated extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in cultured cortical neurons. Therefore, we examined the effect of DAEE treatment on a rat model of spinal cord injury. DAEE (150 μg/kg body weight) administered after hemisection of the spinal cord resulted in improved functional recovery, decreased the lesion size, increased the activation of ERK1/2, and enhanced the expression of bcl-2 and brain-derived neurotrophic factor (BDNF) mRNA in the injury site of the spinal cord. Furthermore, it also increased neuronal survival after spinal cord injury. These results indicate that the possibility that DAEE will become a promising tool for reducing the secondary damage observed following primary physical injury to the spinal cord. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Melatonin Inhibits Neural Cell Apoptosis and Promotes Locomotor Recovery via Activation of the Wnt/β-Catenin Signaling Pathway After Spinal Cord Injury.

PubMed

Shen, Zhaoliang; Zhou, Zipeng; Gao, Shuang; Guo, Yue; Gao, Kai; Wang, Haoyu; Dang, Xiaoqian

2017-08-01

The spinal cord is highly sensitive to spinal cord injury (SCI) by external mechanical damage, resulting in irreversible neurological damage. Activation of the Wnt/β-catenin signaling pathway can effectively reduce apoptosis and protect against SCI. Melatonin, an indoleamine originally isolated from bovine pineal tissue, exerts neuroprotective effects after SCI through activation of the Wnt/β-catenin signaling pathway. In this study, we demonstrated that melatonin exhibited neuroprotective effects on neuronal apoptosis and supported functional recovery in a rat SCI model by activating the Wnt/β-catenin signaling pathway. We found that melatonin administration after SCI significantly upregulated the expression of low-density lipoprotein receptor related protein 6 phosphorylation (p-LRP-6), lymphoid enhancer factor-1 (LEF-1) and β-catenin protein in the spinal cord. Melatonin enhanced motor neuronal survival in the spinal cord ventral horn and improved the locomotor functions of rats after SCI. Melatonin administration after SCI also reduced the expression levels of Bax and cleaved caspase-3 in the spinal cord and the proportion of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) positive cells, but increased the expression level of Bcl-2. These results suggest that melatonin attenuated SCI by activating the Wnt/β-catenin signaling pathway.

Engaging cervical spinal cord networks to re-enable volitional control of hand function in tetraplegic patients

PubMed Central

Lu, Daniel C.; Edgerton, V. Reggie; Modaber, Morteza; AuYong, Nicholas; Morikawa, Erika; Zdunowski, Sharon; Sarino, Melanie E.; Nuwer, Marc R.; Roy, Roland R.; Gerasimenko, Yury

2016-01-01

Background Paralysis of the upper-limbs from spinal cord injury results in an enormous loss of independence in an individual’s daily life. Meaningful improvement in hand function is rare after one year of tetraparesis. Therapeutic developments that result in even modest gains in hand volitional function will significantly impact the quality of life for patients afflicted with high cervical injury. The ability to neuromodulate the lumbosacral spinal circuitry via epidural stimulation in regaining postural function and volitional control of the legs has been recently shown. A key question is whether a similar neuromodulatory strategy can be used to improve volitional motor control of the upper-limbs, i.e., performance of motor tasks considered to be less “automatic” than posture and locomotion. In this study, the effects of cervical epidural stimulation on hand function are characterized in subjects with chronic cervical cord injury. Objective Herein we show that epidural stimulation can be applied to the chronic injured human cervical spinal cord to promote volitional hand function. Methods and results Two subjects implanted with an cervical epidural electrode array demonstrated improved hand strength (approximately three-fold) and volitional hand control in the presence of epidural stimulation. Conclusions The present data are sufficient to suggest that hand motor function in individuals with chronic tetraplegia can be improved with cervical cord neuromodulation and thus should be comprehensively explored as a possible clinical intervention. PMID:27198185

Health behavior in persons with spinal cord injury: development and initial validation of an outcome measure.

PubMed

Pruitt, S D; Wahlgren, D R; Epping-Jordan, J E; Rossi, A L

1998-10-01

To describe the development and initial psychometric properties of a new outcome measure for health behaviors that delay or prevent secondary impairments associated with spinal cord injury (SCI). Persons with SCI were surveyed during routine annual physical evaluations. Veterans Affairs Medical Center Spinal Cord Injury Unit, which specializes in primary care for persons with SCI. Forty-nine persons with SCI, aged 19-73 years, 1-50 years post-SCI. The newly developed Spinal Cord Injury Lifestyle Scale (SCILS). Internal consistency is high (alpha = 0.81). Correlations between clinicians' ratings of participants' health behavior and the new SCILS provide preliminary support for construct validity. The SCILS is a brief, self-report measure of health-related behavior in persons with SCI. It is a promising new outcome measure to evaluate the effectiveness of clinical and educational efforts for health maintenance and prevention of secondary impairments associated with SCI.

7 Tesla 22-channel wrap-around coil array for cervical spinal cord and brainstem imaging.

PubMed

Zhang, Bei; Seifert, Alan C; Kim, Joo-Won; Borrello, Joseph; Xu, Junqian

2017-10-01

Increased signal-to-noise ratio and blood oxygenation level-dependent sensitivity at 7 Tesla (T) have the potential to enable high-resolution imaging of the human cervical spinal cord and brainstem. We propose a new two-panel radiofrequency coil design for these regions to fully exploit the advantages of ultra-high field. A two-panel array, containing four transmit/receive and 18 receive-only elements fully encircling the head and neck, was constructed following simulations demonstrating the B1+ and specific absorption rate (SAR) benefits of two-panel over one-panel arrays. This array was compared with a previously reported posterior-only array and tested for safety using a phantom. Its anatomical, functional, and diffusion MRI performance was demonstrated in vivo. The two-panel array produced more uniform B1+ across the brainstem and cervical spinal cord without compromising SAR, and achieved 70% greater receive sensitivity than the posterior-only array. The two-panel design enabled acceleration of R = 2 × 2 in two dimensions or R = 3 in a single dimension. High quality in vivo anatomical, functional, and diffusion images of the human cervical spinal cord and brainstem were acquired. We have designed and constructed a wrap-around coil array with excellent performance for cervical spinal cord and brainstem MRI at 7T, which enables simultaneous human cervical spinal cord and brainstem functional MRI. Magn Reson Med 78:1623-1634, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Early changes in somatosensory function in spinal pain: a systematic review and meta-analysis.

PubMed

Marcuzzi, Anna; Dean, Catherine M; Wrigley, Paul J; Hush, Julia M

2015-02-01

Alterations in sensory processing have been demonstrated in chronic low back and neck pain. However, it has not been yet systematically summarized how early these changes occur in spinal pain. This systematic review examines the available literature measuring somatosensory function in acute (<6 weeks) and subacute (6-12 weeks) spinal pain. The protocol for this review has been registered on the International Prospective Register of Systematic Reviews (PROSPERO). An electronic search of 4 databases was conducted to retrieve studies assessing somatosensory function by quantitative sensory testing in adults with spinal pain of up to 12 weeks duration. Two reviewers independently screened the studies and assessed the risk of bias. Studies were grouped according to spinal pain condition (whiplash injury, idiopathic neck pain, and nonspecific low back pain), and, where possible, meta-analyses were performed for comparable results. Fifteen studies were included. Sources of bias included lack of assessor blinding, unclear sampling methods, and lack of control for confounders. We found that: (1) there is consistent evidence for thermal and widespread mechanical pain hypersensitivity in the acute stage of whiplash, (2) there is no evidence for pain hypersensitivity in the acute and subacute stage of idiopathic neck pain, although the body of evidence is small, and (3) hyperalgesia and spinal cord hyperexcitability have been detected in early stages of nonspecific low back pain, although evidence about widespread effects are conflicting. Future longitudinal research using multiple sensory modalities and standardized testing may reveal the involvement of somatosensory changes in the development and maintenance of chronic pain.

The Role of Brain-Derived Neurotrophic Factor (BDNF) in the Development of Neurogenic Detrusor Overactivity (NDO)

PubMed Central

Frias, Bárbara; Santos, João; Morgado, Marlene; Sousa, Mónica Mendes; Gray, Susannah M.Y.; McCloskey, Karen D.; Allen, Shelley; Cruz, Francisco

2015-01-01

Neurogenic detrusor overactivity (NDO) is a well known consequence of spinal cord injury (SCI), recognizable after spinal shock, during which the bladder is areflexic. NDO emergence and maintenance depend on profound plastic changes of the spinal neuronal pathways regulating bladder function. It is well known that neurotrophins (NTs) are major regulators of such changes. NGF is the best-studied NT in the bladder and its role in NDO has already been established. Another very abundant neurotrophin is BDNF. Despite being shown that, acting at the spinal cord level, BDNF is a key mediator of bladder dysfunction and pain during cystitis, it is presently unclear if it is also important for NDO. This study aimed to clarify this issue. Results obtained pinpoint BDNF as an important regulator of NDO appearance and maintenance. Spinal BDNF expression increased in a time-dependent manner together with NDO emergence. In chronic SCI rats, BDNF sequestration improved bladder function, indicating that, at later stages, BDNF contributes NDO maintenance. During spinal shock, BDNF sequestration resulted in early development of bladder hyperactivity, accompanied by increased axonal growth of calcitonin gene-related peptide-labeled fibers in the dorsal horn. Chronic BDNF administration inhibited the emergence of NDO, together with reduction of axonal growth, suggesting that BDNF may have a crucial role in bladder function after SCI via inhibition of neuronal sprouting. These findings highlight the role of BDNF in NDO and may provide a significant contribution to create more efficient therapies to manage SCI patients. PMID:25653370

Halo-gravity traction in the treatment of severe spinal deformity: a systematic review and meta-analysis.

PubMed

Yang, Changsheng; Wang, Huafeng; Zheng, Zhaomin; Zhang, Zhongmin; Wang, Jianru; Liu, Hui; Kim, Yongjung Jay; Cho, Samuel

2017-07-01

Halo-gravity traction has been reported to successfully assist in managing severe spinal deformity. This is a systematic review of all studies on halo-gravity traction in the treatment of spinal deformity to provide information for clinical practice. A comprehensive search was conducted for articles on halo-gravity traction in the treatment of spinal deformity according to the PRISMA guidelines. Appropriate studies would be included and analyzed. Preoperative correction rate of spinal deformity, change of pulmonary function and prevalence of complications were the main measurements. Sixteen studies, a total of 351 patients, were included in this review. Generally, the initial Cobb angle was 101.1° in the coronal plane and 80.5° in the sagittal plane, and it was corrected to 49.4° and 56.0° after final spinal fusion. The preoperative correction due to traction alone was 24.1 and 19.3%, respectively. With traction, the flexibility improved 6.1% but postoperatively the patients did not have better correction. Less aggressive procedures and improved pulmonary function were observed in patients with traction. The prevalence of traction-related complications was 22% and three cases of neurologic complication related to traction were noted. The prevalence of total complications related to surgery was 32% and that of neurologic complications was 1%. Partial correction could be achieved preoperatively with halo-gravity traction, and it may help decrease aggressive procedures, improve preoperative pulmonary function, and reduce neurologic complications. However, traction could not increase preoperative flexibility or final correction. Traction-related complications, although usually not severe, were not rare.

Spinal Cord Injury—Past, Present, and Future

PubMed Central

Donovan, William H

2007-01-01

Summary: This special report traces the path of spinal cord injury (SCI) from ancient times through the present and provides an optimistic overview of promising clinical trials and avenues of basic research. The spinal cord injuries of Lord Admiral Sir Horatio Nelson, President James A. Garfield, and General George Patton provide an interesting perspective on the evolution of the standard of care for SCI. The author details the contributions of a wide spectrum of professionals in the United States, Europe, and Australia, as well as the roles of various government and professional organizations, legislation, and overall advances in surgery, anesthesia, trauma care, imaging, pharmacology, and infection control, in the advancement of care for the individual with SCI. PMID:17591221

Targeting L-Selectin to Improve Neurologic and Urologic Function After Spinal Cord Injury

DTIC Science & Technology

2014-10-01

doses of DFA, male C57BL/6 mice were subjected to a 2g weight dropped 7.5 cm onto the exposed spinal cord at the thoracic 9 vertebral level (mild...detect the absence of L-selectin on leukocytes 1 day post-SCI. Male C57BL/6 mice were subjected to a 2g weight dropped 7.5 cm onto the exposed spinal...subjected to a 2g weight dropped 7.5 cm onto the exposed spinal cord at the thoracic 9 vertebral level. DFA (40mg/kg) or vehicle was administered

Making sense out of spinal cord somatosensory development

PubMed Central

Seal, Rebecca P.

2016-01-01

The spinal cord integrates and relays somatosensory input, leading to complex motor responses. Research over the past couple of decades has identified transcription factor networks that function during development to define and instruct the generation of diverse neuronal populations within the spinal cord. A number of studies have now started to connect these developmentally defined populations with their roles in somatosensory circuits. Here, we review our current understanding of how neuronal diversity in the dorsal spinal cord is generated and we discuss the logic underlying how these neurons form the basis of somatosensory circuits. PMID:27702783

Spinal anesthesia in infants: recent developments.

PubMed

Tirmizi, Henna

2015-06-01

Spinal anesthesia has long been described as a well-tolerated and effective means of providing anesthesia for infants undergoing lower abdominal surgery. Now, spinal anesthetics are being used for an increasing variety of surgeries previously believed to require a general anesthetic. This, along with increasing concerns over the neurocognitive effects of general anesthetics on developing brains, suggests that further exploration into this technique and its effects is essential. Exposure to spinal anesthesia in infancy has not shown the same suggestions of neurocognitive detriment as those resulting from general anesthesia. Ultrasound guidance has enhanced spinal technique by providing real-time guidance into the intrathecal space and confirming medication administration location, as well as helping avoid adverse outcomes by identifying aberrant anatomy. Spinal anesthesia provides benefits over general anesthesia, including cardiorespiratory stability, shorter postoperative recovery, and faster return of gastrointestinal function. Early findings of spinal anesthesia exposure in infancy have shown it to have no independent effect on neurocognitive delay as well as to provide sound cardiorespiratory stability. With safer means of administering a spinal anesthetic, such as with ultrasound guidance, it is a readily available and desirable tool for those providing anesthesia to infants.

Spinal Reflexes and Windup In Vitro: Effects of Analgesics and Anesthetics.

PubMed

Rivera-Arconada, Ivan; Roza, Carolina; Lopez-Garcia, Jose A

2016-02-01

The spinal cord is the first relay center for nociceptive information. Following peripheral injury, the spinal cord sensitizes. A sign of spinal sensitization is the hyper-reflexia which develops shortly after injury and can be detected in the isolated spinal cord as a "memory of pain." In this context, it is easy to understand that many analgesic compounds target spinally located sites of action to attain analgesia. In vitro isolated spinal cord preparations have been used for a number of years, and experience on the effects of compounds of diverse pharmacological families on spinal function has accumulated. Recently, we have proposed that the detailed study of spinal segmental reflexes in vitro may produce data relevant to the evaluation of the analgesic potential of novel compounds. In this review, we describe the main features of segmental reflexes obtained in vitro and discuss the effects of compounds of diverse chemical nature and pharmacological properties on such reflexes. Our aim was to compare the different profiles of action of the compounds on segmental reflexes in order to extract clues that may be helpful for pharmacological characterization of novel analgesics. © 2015 John Wiley & Sons Ltd.

Targeting Lumbar Spinal Neural Circuitry by Epidural Stimulation to Restore Motor Function After Spinal Cord Injury.

PubMed

Minassian, Karen; McKay, W Barry; Binder, Heinrich; Hofstoetter, Ursula S

2016-04-01

Epidural spinal cord stimulation has a long history of application for improving motor control in spinal cord injury. This review focuses on its resurgence following the progress made in understanding the underlying neurophysiological mechanisms and on recent reports of its augmentative effects upon otherwise subfunctional volitional motor control. Early work revealed that the spinal circuitry involved in lower-limb motor control can be accessed by stimulating through electrodes placed epidurally over the posterior aspect of the lumbar spinal cord below a paralyzing injury. Current understanding is that such stimulation activates large-to-medium-diameter sensory fibers within the posterior roots. Those fibers then trans-synaptically activate various spinal reflex circuits and plurisegmentally organized interneuronal networks that control more complex contraction and relaxation patterns involving multiple muscles. The induced change in responsiveness of this spinal motor circuitry to any residual supraspinal input via clinically silent translesional neural connections that have survived the injury may be a likely explanation for rudimentary volitional control enabled by epidural stimulation in otherwise paralyzed muscles. Technological developments that allow dynamic control of stimulation parameters and the potential for activity-dependent beneficial plasticity may further unveil the remarkable capacity of spinal motor processing that remains even after severe spinal cord injuries.

Potential of human dental stem cells in repairing the complete transection of rat spinal cord

NASA Astrophysics Data System (ADS)

Yang, Chao; Li, Xinghan; Sun, Liang; Guo, Weihua; Tian, Weidong

2017-04-01

Objective. The adult spinal cord of mammals contains a certain amount of neural precursor cells, but these endogenous cells have a limited capacity for replacement of lost cells after spinal cord injury. The exogenous stem cells transplantation has become a therapeutic strategy for spinal cord repairing because of their immunomodulatory and differentiation capacity. In addition, dental stem cells originating from the cranial neural crest might be candidate cell sources for neural engineering. Approach. Human dental follicle stem cells (DFSCs), stem cells from apical papilla (SCAPs) and dental pulp stem cells (DPSCs) were isolated and identified in vitro, then green GFP-labeled stem cells with pellets were transplanted into completely transected spinal cord. The functional recovery of rats and multiple neuro-regenerative mechanisms were explored. Main results. The dental stem cells, especially DFSCs, demonstrated the potential in repairing the completely transected spinal cord and promote functional recovery after injury. The major involved mechanisms were speculated below: First, dental stem cells inhibited the expression of interleukin-1β to reduce the inflammatory response; second, they inhibited the expression of ras homolog gene family member A (RhoA) to promote neurite regeneration; third, they inhibited the sulfonylurea receptor1 (SUR-1) expression to reduce progressive hemorrhagic necrosis; lastly, parts of the transplanted cells survived and differentiated into mature neurons and oligodendrocytes but not astrocyte, which is beneficial for promoting axons growth. Significance. Dental stem cells presented remarkable tissue regenerative capability after spinal cord injury through immunomodulatory, differentiation and protection capacity.

Spinal epidural angiolipomas: Clinical characteristics, management and outcomes

PubMed Central

Bouali, Sofiene; Maatar, Nidhal; Bouhoula, Asma; Abderrahmen, Khansa; Said, Imed Ben; Boubaker, Adnen; Kallel, Jalel; Jemel, Hafedh

2016-01-01

Purpose: The spinal epidural angiolipomas are rare expansive processes made of mature lipomatous and angiomatous elements. They often have a benign character. Their etiology, pathogenesis remains uncertain, and it is a cause of spinal cord compression. The magnetic resonance imaging is the most important neuroradiological examination. Histological examination is the only examination to confirm the diagnosis. Surgery is the treatment of choice. Methods: A retrospective study of all patients operated on for a spinal epidural angiolipoma at the Department of Neurosurgery at the National Institute of Neurology of Tunis between January 2000 and December 2014 (15 years) was performed. The aim of this study is to describe the clinical, radiological, histological characteristics and the treatment of this tumor. Results: A total of nine patients were operated from January 01, 2000 to November 30, 2014. The average age of our patients was 51 years with ages that ranged from 29 to 65 with a male predominance. The period between onset of symptoms and diagnosis ranged from 24 months with an average 12 months. Posterior localization of the tumor was seen in all patients. Surgical resection was performed for all cases. The postoperative course has been satisfactory, with a complete recovery of neurological functions in all patients. Conclusions: The spinal epidural angiolipomas is rare expansive process causing spinal cord compression. Treatment is exclusively surgical resection. The functional outcome of spinal epidural angiolipomas is particularly favorable with a complete neurological recovery is if the patient was quickly operated. PMID:27695535

Spinal epidural angiolipomas: Clinical characteristics, management and outcomes.

PubMed

Bouali, Sofiene; Maatar, Nidhal; Bouhoula, Asma; Abderrahmen, Khansa; Said, Imed Ben; Boubaker, Adnen; Kallel, Jalel; Jemel, Hafedh

2016-01-01

The spinal epidural angiolipomas are rare expansive processes made of mature lipomatous and angiomatous elements. They often have a benign character. Their etiology, pathogenesis remains uncertain, and it is a cause of spinal cord compression. The magnetic resonance imaging is the most important neuroradiological examination. Histological examination is the only examination to confirm the diagnosis. Surgery is the treatment of choice. A retrospective study of all patients operated on for a spinal epidural angiolipoma at the Department of Neurosurgery at the National Institute of Neurology of Tunis between January 2000 and December 2014 (15 years) was performed. The aim of this study is to describe the clinical, radiological, histological characteristics and the treatment of this tumor. A total of nine patients were operated from January 01, 2000 to November 30, 2014. The average age of our patients was 51 years with ages that ranged from 29 to 65 with a male predominance. The period between onset of symptoms and diagnosis ranged from 24 months with an average 12 months. Posterior localization of the tumor was seen in all patients. Surgical resection was performed for all cases. The postoperative course has been satisfactory, with a complete recovery of neurological functions in all patients. The spinal epidural angiolipomas is rare expansive process causing spinal cord compression. Treatment is exclusively surgical resection. The functional outcome of spinal epidural angiolipomas is particularly favorable with a complete neurological recovery is if the patient was quickly operated.

Is neuroinflammation in the injured spinal cord different than in the brain? Examining intrinsic differences between the brain and spinal cord.

PubMed

Zhang, B; Gensel, J C

2014-08-01

The field of neuroimmunology is rapidly advancing. There is a growing appreciation for heterogeneity, both in inflammatory composition and region-specific inflammatory responses. This understanding underscores the importance of developing targeted immunomodulatory therapies for treating neurological disorders. Concerning neurotrauma, there is a dearth of publications directly comparing inflammatory responses in the brain and spinal cord after injury. The question therefore remains as to whether inflammatory cells responding to spinal cord vs. brain injury adopt similar functions and are therefore amenable to common therapies. In this review, we address this question while revisiting and modernizing the conclusions from publications that have directly compared inflammation across brain and spinal cord injuries. By examining molecular differences, anatomical variations, and inflammatory cell phenotypes between the injured brain and spinal cord, we provide insight into how neuroinflammation relates to neurotrauma and into fundamental differences between the brain and spinal cord. Copyright © 2014 Elsevier Inc. All rights reserved.

Monitoring somatosensory evoked potentials in spinal cord ischemia-reperfusion injury

PubMed Central

Ji, Yiming; Meng, Bin; Yuan, Chenxi; Yang, Huilin; Zou, Jun

2013-01-01

It remains unclear whether spinal cord ischemia-reperfusion injury caused by ischemia and other non-mechanical factors can be monitored by somatosensory evoked potentials. Therefore, we monitored spinal cord ischemia-reperfusion injury in rabbits using somatosensory evoked potential detection technology. The results showed that the somatosensory evoked potential latency was significantly prolonged and the amplitude significantly reduced until it disappeared during the period of spinal cord ischemia. After reperfusion for 30–180 minutes, the amplitude and latency began to gradually recover; at 360 minutes of reperfusion, the latency showed no significant difference compared with the pre-ischemic value, while the somatosensory evoked potential amplitude in-creased, and severe hindlimb motor dysfunctions were detected. Experimental findings suggest that changes in somatosensory evoked potential latency can reflect the degree of spinal cord ischemic injury, while the amplitude variations are indicators of the late spinal cord reperfusion injury, which provide evidence for the assessment of limb motor function and avoid iatrogenic spinal cord injury. PMID:25206629

Lumbar spinal mobility changes among adults with advancing age

PubMed Central

Saidu, Ismaila Adamu; Maduagwu, Stanley Monday; Abbas, Abdullahi Digil; Adetunji, Omotayo O.; Jajere, Abdurahman Mohammed

2011-01-01

Background: Limitations in spinal mobility can interfere with the attainment of important functional skills and activities of daily living and restrictions in spinal mobility are usually the earliest and reliable indicator of diseases. Objective: The aim of this study was to determine the differences of lumbar spinal mobility among healthy adults with advancing age. Materials and Methods: The modified Schober's method was used to measure anterior flexion. The guideline of the American Academy of Orthopaedic Surgeons was adapted to measure lateral flexion and extension. Results: The results of this study indicate that spinal mobility decreases with advancing age. The most significant (P < 0.05) differences occurred between the two youngest and the two oldest age categories. Conclusion: Using these data, we developed normative values of spinal mobility for each sex and age group. This study helps the clinicians to understand and correlate the restrictions of lumbar spinal mobility due to age and differentiate the limitations due to disease. PMID:22408334

Spinal cord injury rehabilitation in Riyadh, Saudi Arabia: Time to rehabilitation admission, length of stay and functional independence

PubMed Central

Mahmoud, Husam; Qannam, Hazem; Mortenson, Ben

2017-01-01

Objectives 1) To describe functional status, length of stay (LOS), and time to rehabilitation admission trends. 2) To identify independent predictors of motor function following rehabilitation for traumatic and nontraumatic spinal cord injury (SCI). Participants Adult patients with SCI discharged from inpatient rehabilitation between 2009–2014. Design Retrospective cohort study. Setting Spinal injury rehabilitation unit at the King Fahad Medical City, Riyadh, Saudi Arabia. Methods From retrospective chart reviews of 312 traumatic and 106 nontraumatic SCI, we extracted information on time from injury to rehabilitation admission, rehabilitation LOS, and Functional Independence Measure (FIM) score (admission and discharge). Additionally we collected information on SCI patients’ demographics and injury characteristics. Hierarchical regression was employed to investigate variables associated with FIM motor score at discharge for traumatic SCI and nontraumatic SCI. Outcome measures FIM motor score measured at discharge. Results Mean and median days from injury to rehabilitation admission were not significantly different for traumatic SCI (377±855, 150) and nontraumatic SCI (288±403, 176). Mean and median days for rehabilitation LOS were significantly longer for traumatic SCI (85±60, 70) compared to nontraumatic SCI (64±59, 49) (p=…..). FIM scores improved significantly from admission to discharge in both groups. For individuals with traumatic SCI, after accounting for admission FIM motor score, tetraplegia and time from injury to rehabilitation, admission had a significant but small negative association with discharge FIM motor score. For individuals with nontraumatic SCI, increasing age and AIS score of A or B had a significant negative association with discharge FIM motor score. LOS in rehabilitation was not a significant contributor for either model. Conclusions Decreasing the time from injury to rehabilitation admission may improve outcomes for those with traumatic SCI. Since time spent in rehabilitation was shorter than most other countries, a change in practice in this area may be warranted. Developing new strategies to improve outcomes for older patients with nontraumatic SCI would also be beneficial. PMID:28139661

Reticular formation responses to magnetic brain stimulation of primary motor cortex

PubMed Central

Fisher, Karen M; Zaaimi, Boubker; Baker, Stuart N

2012-01-01

Transcranial magnetic stimulation (TMS) of cerebral cortex is a popular technique for the non-invasive investigation of motor function. TMS is often assumed to influence spinal circuits solely via the corticospinal tract. We were interested in possible trans-synaptic effects of cortical TMS on the ponto-medullary reticular formation in the brainstem, which is the source of the reticulospinal tract and could also generate spinal motor output. We recorded from 210 single units in the reticular formation of three anaesthetized macaque monkeys whilst TMS was performed over primary motor cortex. Short latency responses were observed consistent with activation of a cortico-reticular pathway. However, we also demonstrated surprisingly powerful responses at longer latency, which often appeared at lower threshold than the earlier effects. These late responses seemed to be generated partly as a consequence of the sound click made by coil discharge, and changed little with coil location. This novel finding has implications for the design of future studies using TMS, as well as suggesting a means of non-invasively probing an otherwise inaccessible important motor centre. PMID:22674723

Reticular formation responses to magnetic brain stimulation of primary motor cortex.

PubMed

Fisher, Karen M; Zaaimi, Boubker; Baker, Stuart N

2012-08-15

Transcranial magnetic stimulation (TMS) of cerebral cortex is a popular technique for the non-invasive investigation of motor function. TMS is often assumed to influence spinal circuits solely via the corticospinal tract. We were interested in possible trans-synaptic effects of cortical TMS on the ponto-medullary reticular formation in the brainstem, which is the source of the reticulospinal tract and could also generate spinal motor output. We recorded from 210 single units in the reticular formation of three anaesthetized macaque monkeys whilst TMS was performed over primary motor cortex. Short latency responses were observed consistent with activation of a cortico-reticular pathway. However, we also demonstrated surprisingly powerful responses at longer latency, which often appeared at lower threshold than the earlier effects. These late responses seemed to be generated partly as a consequence of the sound click made by coil discharge, and changed little with coil location. This novel finding has implications for the design of future studies using TMS, as well as suggesting a means of non-invasively probing an otherwise inaccessible important motor centre.

Human dental pulp stem cells transplantation combined with treadmill training in rats after traumatic spinal cord injury

PubMed Central

Nicola, F.C.; Rodrigues, L.P.; Crestani, T.; Quintiliano, K.; Sanches, E.F.; Willborn, S.; Aristimunha, D.; Boisserand, L.; Pranke, P.; Netto, C.A.

2016-01-01

Spinal cord injury (SCI) is a disabling condition resulting in deficits of sensory and motor functions, and has no effective treatment. Considering that protocols with stem cell transplantation and treadmill training have shown promising results, the present study evaluated the effectiveness of stem cells from human exfoliated deciduous teeth (SHEDs) transplantation combined with treadmill training in rats with experimental spinal cord injury. Fifty-four Wistar rats were spinalized using NYU impactor. The rats were randomly distributed into 5 groups: Sham (laminectomy with no SCI, n=10); SCI (laminectomy followed by SCI, n=12); SHEDs (SCI treated with SHEDs, n=11); TT (SCI treated with treadmill training, n=11); SHEDs+TT (SCI treated with SHEDs and treadmill training; n=10). Treatment with SHEDs alone or in combination with treadmill training promoted functional recovery, reaching scores of 15 and 14, respectively, in the BBB scale, being different from the SCI group, which reached 11. SHEDs treatment was able to reduce the cystic cavity area and glial scar, increase neurofilament. Treadmill training alone had no functional effectiveness or tissue effects. In a second experiment, the SHEDs transplantation reduced the TNF-α levels in the cord tissue measured 6 h after the injury. Contrary to our hypothesis, treadmill training either alone or in combination, caused no functional improvement. However, SHEDs showed to be neuroprotective, by the reduction of TNF-α levels, the cystic cavity and the glial scar associated with the improvement of motor function after SCI. These results provide evidence that grafted SHEDs might be an effective therapy to spinal cord lesions, with possible anti-inflammatory action. PMID:27509306

Human dental pulp stem cells transplantation combined with treadmill training in rats after traumatic spinal cord injury.

PubMed

Nicola, F C; Rodrigues, L P; Crestani, T; Quintiliano, K; Sanches, E F; Willborn, S; Aristimunha, D; Boisserand, L; Pranke, P; Netto, C A

2016-08-08

Spinal cord injury (SCI) is a disabling condition resulting in deficits of sensory and motor functions, and has no effective treatment. Considering that protocols with stem cell transplantation and treadmill training have shown promising results, the present study evaluated the effectiveness of stem cells from human exfoliated deciduous teeth (SHEDs) transplantation combined with treadmill training in rats with experimental spinal cord injury. Fifty-four Wistar rats were spinalized using NYU impactor. The rats were randomly distributed into 5 groups: Sham (laminectomy with no SCI, n=10); SCI (laminectomy followed by SCI, n=12); SHEDs (SCI treated with SHEDs, n=11); TT (SCI treated with treadmill training, n=11); SHEDs+TT (SCI treated with SHEDs and treadmill training; n=10). Treatment with SHEDs alone or in combination with treadmill training promoted functional recovery, reaching scores of 15 and 14, respectively, in the BBB scale, being different from the SCI group, which reached 11. SHEDs treatment was able to reduce the cystic cavity area and glial scar, increase neurofilament. Treadmill training alone had no functional effectiveness or tissue effects. In a second experiment, the SHEDs transplantation reduced the TNF-α levels in the cord tissue measured 6 h after the injury. Contrary to our hypothesis, treadmill training either alone or in combination, caused no functional improvement. However, SHEDs showed to be neuroprotective, by the reduction of TNF-α levels, the cystic cavity and the glial scar associated with the improvement of motor function after SCI. These results provide evidence that grafted SHEDs might be an effective therapy to spinal cord lesions, with possible anti-inflammatory action.

Observational study of the effectiveness of spinal cord injury rehabilitation using the Spinal Cord Injury-Ability Realization Measurement Index.

PubMed

Scivoletto, G; Bonavita, J; Torre, M; Baroncini, I; Tiberti, S; Maietti, E; Laurenza, L; China, S; Corallo, V; Guerra, F; Buscaroli, L; Candeloro, C; Brunelli, E; Catz, A; Molinari, M

2016-06-01

Retrospective observational study. The objective of this study was to determine the rehabilitation potential and the extent to which it is realized in a cohort of spinal cord injury patients using the Spinal Cord Injury-Ability Realization Measurement Index (SCI-ARMI) and to study the clinical factors that influence this realization. Two spinal units in Italy. Consecutive patients were assessed at the end of an in-patient rehabilitation program using the Spinal Cord Independence Measure and the International Standards for Neurological Classification of Spinal Cord Injury. On the basis of these data and of the age and gender of the patients, we calculated the SCI-ARMI score. Regression analyses were performed to study the relationship between clinical factors and the extent to which rehabilitation potential is realized. We examined the data for 306 patients. Most patients were discharged without having reached their rehabilitation potential, with an SCI-ARMI score <80%. SCI-ARMI scores at discharge were positively influenced by etiology and the lesion level and correlated negatively with lesion severity and the presence of complications during rehabilitation. The SCI-ARMI is an effective tool that can be used to measure the achievement of rehabilitation potential in SCI patients and to identify groups of patients who are at risk of not meeting their rehabilitative potential.

[Low-dose hypobaric spinal anesthesia for anorectal surgery in jackknife position: levobupivacaine-fentanyl compared to lidocaine-fentanyl].

PubMed

de Santiago, J; Santos-Yglesias, J; Girón, J; Jiménez, A; Errando, C L

2010-11-01

To compare the percentage of patients who were able to bypass the postoperative intensive care recovery unit after selective spinal anesthesia with lidocaine-fentanyl versus levobupivacaine-fentanyl for anorectal surgery in jackknife position. Randomized double-blind clinical trial comparing 2 groups of 30 patients classified ASA 1-2. One group received 18 mg of 0.6% lidocaine plus 10 microg of fentanyl while the other group received 3 mg of 0.1% levobupivacaine plus 10 microg of fentanyl. Intraoperative variables were time of start of surgery, maximum extension of sensory blockade, requirement for rescue analgesics, and hemodynamic events. The level of sensory blockade was recorded at 5, 10, and 15 minutes after the start of surgery and at the end of the procedure. The degrees of postoperative motor blockade and proprioception were recorded, as were the results of the Romberg test and whether or not the patient was able to bypass the postoperative recovery unit. Also noted were times of start of ambulation and discharge, complications, and postoperative satisfaction. Intraoperative variables did not differ significantly between groups, and all patients in both groups bypassed the postoperative recovery unit. Times until walking and discharge home, complications, and overall satisfaction after surgery were similar in the 2 groups. Both spinal anesthetic solutions provide effective, selective anesthesia and are associated with similar rates of recovery care unit bypass after anorectal surgery in jackknife position.

Spinal Injury: Regeneration, Recovery, and a Possible New Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, Avis

Spinal injury is most frequent in young healthy men, desperate to walk. Most treatments have focused on regeneration of the injured axons, but no one has as yet achieved success with this approach. However, in the lamprey, a primitive fish with a spinal cord having all the critical features of the human spinal cored, spinal injury is followed by complete regeneration of injured axons. Additionally, the animal recovers the ability to swim, and in many, the swimming is normal. Unfortunately, in most others, it is highly abnormal. This talk will review evidence from the abnormal regeneration, why it bespeaks difficultiesmore » heretofore not considered, and suggest an alternate approach for the near future. In so doing, the speaker will introduce the normal function of the spinal cord, what happens in normal and abnormal regeneration, and the new techniques that employ methods from neuromorphic engineering, a synthesis of neuroscience and engineering to engineer smart devices.« less

Spinal Injury: Regeneration, Recovery, and a Possible New Approach

ScienceCinema

Cohen, Avis [University of Maryland, College Park, Maryland, United States

2017-12-09

Spinal injury is most frequent in young healthy men, desperate to walk. Most treatments have focused on regeneration of the injured axons, but no one has as yet achieved success with this approach. However, in the lamprey, a primitive fish with a spinal cord having all the critical features of the human spinal cored, spinal injury is followed by complete regeneration of injured axons. Additionally, the animal recovers the ability to swim, and in many, the swimming is normal. Unfortunately, in most others, it is highly abnormal. This talk will review evidence from the abnormal regeneration, why it bespeaks difficulties heretofore not considered, and suggest an alternate approach for the near future. In so doing, the speaker will introduce the normal function of the spinal cord, what happens in normal and abnormal regeneration, and the new techniques that employ methods from neuromorphic engineering, a synthesis of neuroscience and engineering to engineer smart devices.

Spinal Cord Ischemia Secondary to Hypovolemic Shock

PubMed Central

Kapoor, Siddhant; Koh, Roy KM; Yang, Eugene WR; Hee, Hwan-Tak

2014-01-01

A 44-year-old male presented with symptoms of spinal cord compression secondary to metastatic prostate cancer. An urgent decompression at the cervical-thoracic region was performed, and there were no complications intraoperatively. Three hours postoperatively, the patient developed acute bilateral lower-limb paralysis (motor grade 0). Clinically, he was in class 3 hypovolemic shock. An urgent magnetic resonance imaging (MRI) was performed, showing no epidural hematoma. He was managed aggressively with medical therapy to improve his spinal cord perfusion. The patient improved significantly, and after one week, he was able to regain most of his motor functions. Although not commonly reported, spinal cord ischemia post-surgery should be recognized early, especially in the presence of hypovolemic shock. MRI should be performed to exclude other potential causes of compression. Spinal cord ischemia needs to be managed aggressively with medical treatment to improve spinal cord perfusion. The prognosis depends on the severity of deficits, and is usually favorable. PMID:25558328

Effect of Spinal Manipulation on Pelvic Floor Functional Changes in Pregnant and Nonpregnant Women: A Preliminary Study.

PubMed

Haavik, Heidi; Murphy, Bernadette A; Kruger, Jennifer

2016-06-01

The aim of this study was to investigate whether a single session of spinal manipulation of pregnant women can alter pelvic floor muscle function as measured using ultrasonographic imaging. In this preliminary, prospective, comparative study, transperineal ultrasonographic imaging was used to assess pelvic floor anatomy and function in 11 primigravid women in their second trimester recruited via notice boards at obstetric caregivers, pregnancy keep-fit classes, and word of mouth and 15 nulliparous women recruited from a convenience sample of female students at the New Zealand College of Chiropractic. Following bladder voiding, 3-/4-dimensional transperineal ultrasonography was performed on all participants in the supine position. Levator hiatal area measurements at rest, on maximal pelvic floor contraction, and during maximum Valsalva maneuver were collected before and after either spinal manipulation or a control intervention. Levator hiatal area at rest increased significantly (P < .05) after spinal manipulation in the pregnant women, with no change postmanipulation in the nonpregnant women at rest or in any of the other measured parameters. Spinal manipulation of pregnant women in their second trimester increased the levator hiatal area at rest and thus appears to relax the pelvic floor muscles. This did not occur in the nonpregnant control participants, suggesting that it may be pregnancy related. Copyright © 2016. Published by Elsevier Inc.

Neurogenin3 restricts serotonergic neuron differentiation to the hindbrain.

PubMed

Carcagno, Abel L; Di Bella, Daniela J; Goulding, Martyn; Guillemot, Francois; Lanuza, Guillermo M

2014-11-12

The development of the nervous system is critically dependent on the production of functionally diverse neuronal cell types at their correct locations. In the embryonic neural tube, dorsoventral signaling has emerged as a fundamental mechanism for generating neuronal diversity. In contrast, far less is known about how different neuronal cell types are organized along the rostrocaudal axis. In the developing mouse and chick neural tube, hindbrain serotonergic neurons and spinal glutamatergic V3 interneurons are produced from ventral p3 progenitors, which possess a common transcriptional identity but are confined to distinct anterior-posterior territories. In this study, we show that the expression of the transcription factor Neurogenin3 (Neurog3) in the spinal cord controls the correct specification of p3-derived neurons. Gain- and loss-of-function manipulations in the chick and mouse embryo show that Neurog3 switches ventral progenitors from a serotonergic to V3 differentiation program by repressing Ascl1 in spinal p3 progenitors through a mechanism dependent on Hes proteins. In this way, Neurog3 establishes the posterior boundary of the serotonergic system by actively suppressing serotonergic specification in the spinal cord. These results explain how equivalent p3 progenitors within the hindbrain and the spinal cord produce functionally distinct neuron cell types. Copyright © 2014 the authors 0270-6474/14/3415223-11$15.00/0.

Development of an Animal Model of Thoracolumbar Burst Fracture-Induced Acute Spinal Cord Injury

DTIC Science & Technology

2016-07-01

Final PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for...MONITOR’S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12...subjected to spinal cord impact with a custom-made controlled spinal cord impactor and balloon compression. Neurological function was assessed for

Clinical Trials Network / Building Infrastructure to Accelerate Transfer of Basic Research in Spinal Cord Injury (SCI) to Clinical Practice

DTIC Science & Technology

2015-05-01

Glasgow Coma Scale (GCS) and of associated injuries with the Abbreviated Injury Scale . The American Spinal Injury Association impairment scale (AIS) is...registry protocol includes: the AIS Impairment Scale , and where appropriate, the Functional Independence Measure FIM™, the Spinal Cord Independence...have been achieved with the registry. Enrollment of 762 participants has demonstrated that is feasible to acquire prospective standardized research

Comparison of the Wake-up Test and Combined TES-MEP and CSEP Monitoring in Spinal Surgery.

PubMed

Chen, Bailing; Chen, Yuguang; Yang, Junlin; Xie, Denghui; Su, Haihua; Li, Fobao; Wan, Yong; Peng, Xinsheng; Zheng, Zhaomin

2015-11-01

A retrospective clinical analysis. The aim of this study was to compare the effectiveness of the wake-up test with that of combined monitoring of transcranial electrical stimulation motor evoked potentials (TES-MEP) and cortical somatosensory evoked potentials (CSEP) in spinal surgery. TES-MEP/CSEP combined monitoring is being increasingly recognized as the ideal approach to detect spinal neurophysiological compromise during spinal surgery; however, as a result the merit of the wake-up test is now in doubt. TES-MEP/CSEP combined monitoring was performed simultaneously in 426 patients who underwent spinal surgery at our department, and wake-up tests were conducted on 23 patients because of positive neurophysiological monitoring results with uncertain causes or persistent positive monitoring findings after all potential causes had been resolved. Preoperative and postoperative neurological examinations were performed as the gold standard to detect irreversible spinal function compromise. All data were collected to compare the efficiency of TES-MEP/CSEP combined monitoring with that of the wake-up test. Positive results of TES-MEP/CSEP combined monitoring were recorded in 64 cases. Among them, the positive monitoring findings agreed with the results of the neurological examination in 51 cases, and the monitoring results did not match that of neurological examination in 13 cases. No false-negative result was observed. The sensitivity of TES-MEP/CSEP monitoring was 100%, the specificity was 96.5%, and the Youden index was 0.965. Wake-up tests were conducted in 23 cases. In 8 patients the positive monitoring findings completely matched the postoperative neurological examination results. In contrast, in the other 15 cases with negative neurophysiological monitoring results, only 9 patients retained intact neurological function and 6 patients suffered compromised neurological function. The sensitivity of the wake-up test was 57.1%, the specificity was 100%, and the Youden index was 0.571. Combined TES-MEP and CSEP monitoring, with its high sensitivity and specificity, is an effective method for monitoring spinal function during surgery and should be the preferred choice. The wake-up test is a useful complementary method for monitoring because of its high specificity.

Chiropractic biophysics technique: a linear algebra approach to posture in chiropractic.

PubMed

Harrison, D D; Janik, T J; Harrison, G R; Troyanovich, S; Harrison, D E; Harrison, S O

1996-10-01

This paper discusses linear algebra as applied to human posture in chiropractic, specifically chiropractic biophysics technique (CBP). Rotations, reflections and translations are geometric functions studied in vector spaces in linear algebra. These mathematical functions are termed rigid body transformations and are applied to segmental spinal movement in the literature. Review of the literature indicates that these linear algebra concepts have been used to describe vertebral motion. However, these rigid body movers are presented here as applying to the global postural movements of the head, thoracic cage and pelvis. The unique inverse functions of rotations, reflections and translations provide a theoretical basis for making postural corrections in neutral static resting posture. Chiropractic biophysics technique (CBP) uses these concepts in examination procedures, manual spinal manipulation, instrument assisted spinal manipulation, postural exercises, extension traction and clinical outcome measures.

Spinal anaesthesia with a micro-catheter in high-risk patients undergoing colorectal cancer and other major abdominal surgery.

PubMed

Kumar, Chandra M; Corbett, William A; Wilson, Robert G

2008-08-01

Extended spinal anaesthesia using a spinal micro-catheter was used as a primary method of anaesthesia for elective colorectal cancer surgery in 68 high risk patients over a 14-year period in our institution. The technique was also useful in eight elective and 13 emergency abdominal surgeries. All patients suffered from severe chronic obstructive airway disease requiring multiple inhalers and drugs (ASA III). Thirty nine of these patients also suffered from angina, myocardial infarction, diabetes and other systemic diseases (ASA IV). Surgery included right hemicolectomy, left hemicolectomy, total colectomy, sigmoid colectomy, Hartman's resection, anterior resection of rectum, abdominoperineal resection, cholecystectomy (open and laparoscopic) and obstructed inguinal hernia requiring laparotomy. Spinal anaesthesia was performed under strict aseptic conditions with a 22 gauge spinal needle with a mixture consisting of 2.75ml of 0.5% heavy bupivacaine and 0.25ml of fentanyl (25microg). This was followed by placement of a spinal micro-catheter and the duration of anaesthesia was extended by intermittent injection of 0.5% isobaric bupivacaine. Brief hypotension occurred in 12.4% of patients during the establishment of anaesthetic block height to T6-7 and was duly treated with intravenous administration of fluid and ephedrine hydrochloride. Good anaesthesia resulted in all patients except for brief discomfort in some patients during hemicolectomy surgery possibly due to the dissection and traction on the peritoneum causing irritation to the diaphragm. The use of sedation was avoided. General anaesthesia was administered in one patient and this patient required postoperative ventilation and cardiovascular support in the Intensive Care Unit. The spinal micro-catheter was removed at the end of surgery. Postoperative pain relief was obtained by administering intravenous morphine through a patient controlled analgesia machine in the critical care ward area (High Dependency Unit). There was a low incidence of minor postoperative side effects such as nausea (14.6%), vomiting (7.9%), minor post dural puncture headache (5.6%) and pruritus (5.6%). We conclude that spinal anaesthesia with a micro-catheter may be used as a primary method of anaesthesia for colorectal cancer surgery and other major abdominal surgery in high-risk patients for whom general anaesthesia would be associated with higher morbidity and mortality.

Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats.

PubMed

Gad, Parag; Choe, Jaehoon; Nandra, Mandheerej Singh; Zhong, Hui; Roy, Roland R; Tai, Yu-Chong; Edgerton, V Reggie

2013-01-21

Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array. We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1-100 Hz and 1-10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats. In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia. Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles.

Convection-enhanced delivery of a hydrophilic nitrosourea ameliorates deficits and suppresses tumor growth in experimental spinal cord glioma models.

PubMed

Ogita, Shogo; Endo, Toshiki; Sugiyama, Shinichiro; Saito, Ryuta; Inoue, Tomoo; Sumiyoshi, Akira; Nonaka, Hiroi; Kawashima, Ryuta; Sonoda, Yukihiko; Tominaga, Teiji

2017-05-01

Convection-enhanced delivery (CED) is a technique allowing local infusion of therapeutic agents into the central nervous system, circumventing the blood-brain or spinal cord barrier. To evaluate the utility of nimustine hydrochloride (ACNU) CED in controlling tumor progression in an experimental spinal cord glioma model. Toxicity studies were performed in 42 rats following the administration of 4 μl of ACNU CED into the mid-thoracic spinal cord at concentrations ranging from 0.1 to 10 mg/ml. Behavioral analyses and histological evaluations were performed to assess ACNU toxicity in the spinal cord. A survival study was performed in 32 rats following the implantation of 9 L cells into the T8 spinal cord. Seven days after the implantation, rats were assigned to four groups: ACNU CED (0.25 mg/ml; n = 8); ACNU intravenous (i.v.) (0.4 mg; n = 8); saline CED (n = 8); saline i.v. (n = 8). Hind limb movements were evaluated daily in all rats for 21 days. Tumor sizes were measured histologically. The maximum tolerated ACNU concentration was 0.25 mg/ml. Preservation of hind limb motor function and tumor growth suppression was observed in the ACNU CED (0.25 mg/ml) and ACNU i.v. groups. Antitumor effects were more prominent in the ACNU CED group especially in behavioral analyses (P < 0.05; log-rank test). ACNU CED had efficacy in controlling tumor growth and preserving neurological function in an experimental spinal cord tumor model. ACNU CED can be a viable treatment option for spinal cord high-grade glioma.

Effects of sex on the incidence and prognosis of spinal meningiomas: a Surveillance, Epidemiology, and End Results study.

PubMed

Westwick, Harrison J; Shamji, Mohammed F

2015-09-01

Most spinal meningiomas are intradural lesions in the thoracic spine that present with both local pain and myelopathy. By using the large prospective Surveillance, Epidemiology, and End Results (SEER) database, the authors studied the incidence of spinal meningiomas and examined demographic and treatment factors predictive of death. Using SEER*Stat software, the authors queried the SEER database for cases of spinal meningioma between 2000 and 2010. From the results, tumor incidence and demographic statistics were computed; incidence was analyzed as a function of tumor location, pathology, age, sex, and malignancy code. Survival was analyzed by using a Cox proportional hazards ratio in SPSS for age, sex, marital status, primary site, size quartile, treatment modality, and malignancy code. In this analysis, significance was set at a p value of 0.05. The 1709 spinal meningiomas reported in the SEER database represented 30.7% of all primary intradural spinal tumors and 7.9% of all meningiomas. These meningiomas occurred at an age-adjusted incidence of 0.193 (95% CI 0.183-0.202) per 100,000 population and were closely related to sex (337 [19.7%] male patients and 1372 [80.3%] female patients). The Cox hazard function for mortality in males was higher (2.4 [95% CI1.7-3.5]) and statistically significant, despite the lower lesion incidence in males. All-cause survival was lowest in patients older than 80 years. Primary site and treatment modality were not significant predictors of mortality. Spinal meningiomas represent a significant fraction of all primary intradural spinal tumors and of all meningiomas. The results of this study establish the association of lesion incidence and survival with sex, with a less frequent incidence in but greater mortality among males.

Sexual Functioning in Men Living with a Spinal Cord Injury-A Narrative Literature Review.

PubMed

Sunilkumar, M M; Boston, Patricia; Rajagopal, M R

2015-01-01

Sexual dysfunction is a major concern for Indian men living with a spinal cord injury. To examine the literature related to sexuality traumatic cord injury and its impact on sexual functioning. Databases using Cumulative Index to Nursing and Allied Health Literature (CINAHL) 2000-2012, Medline 1989-2012, Applied Social Sciences Index and Abstracts (ASSIA) 1989-2012 and Google Scholar were the search engines used used for literature review. The search yielded a total of 457 articles and only 75 of them were found relevant. The minimum number of articles required to meet the inclusion criteria for this review was 25-30 articles. Out of the 75 articles, 33 were considered relevant or related to the topic of sexual functioning, spinal cord injury, and paraplegia. Six areas were identified: Sexual stigmatization, physiological barriers to sexual satisfaction, clinical aspects of sexual functioning, biomedical approaches to sexual dysfunction, partner satisfaction, and lack of accessibility to sexual education. Spinal cord injury and sexual functioning affects a large segment of the male Indian population, yet most current research focuses on quantitative measurement with the emphasis on ejaculatory dysfunction, orgasm impairment, incontinence, and other physiological dysfunction. Further research is needed to address the subjective accounts of patients themselves with respect to the emotional and social impact of sexual disability. This would help to identify the best possible outcomes for both treatment and rehabilitation.

The angiopoietin1-Akt pathway regulates barrier function of the cultured spinal cord microvascular endothelial cells through Eps8.

PubMed

Liu, Xinchun; Zhou, Xiaoshu; Yuan, Wei

2014-10-15

In mammalian central nervous system (CNS), the integrity of the blood-spinal cord barrier (BSCB), formed by tight junctions (TJs) between adjacent microvascular endothelial cells near the basement membrane of capillaries and the accessory structures, is important for relatively independent activities of the cellular constituents inside the spinal cord. The barrier function of the BSCB are tightly regulated and coordinated by a variety of physiological or pathological factors, similar with but not quite the same as its counterpart, the blood-brain barrier (BBB). Herein, angiopoietin 1 (Ang1), an identified ligand of the endothelium-specific tyrosine kinase receptor Tie-2, was verified to regulate barrier functions, including permeability, junction protein interactions and F-actin organization, in cultured spinal cord microvascular endothelial cells (SCMEC) of rat through the activity of Akt. Besides, these roles of Ang1 in the BSCB in vitro were found to be accompanied with an increasing expression of epidermal growth factor receptor pathway substrate 8 (Eps8), an F-actin bundling protein. Furthermore, the silencing of Eps8 by lentiviral shRNA resulted in an antagonistic effect vs. Ang1 on the endothelial barrier function of SCMEC. In summary, the Ang1-Akt pathway serves as a regulator in the barrier function modulation of SCMEC via the actin-binding protein Eps8. Copyright © 2014 Elsevier Inc. All rights reserved.

Upper limb module in non-ambulant patients with spinal muscular atrophy: 12 month changes.

PubMed

Sivo, Serena; Mazzone, Elena; Antonaci, Laura; De Sanctis, Roberto; Fanelli, Lavinia; Palermo, Concetta; Montes, Jacqueline; Pane, Marika; Mercuri, Eugenio

2015-03-01

Recent studies have suggested that in non-ambulant patients affected by spinal muscular atrophy the Upper Limb Module can increase the range of activities assessed by the Hammersmith Functional Motor Scale Expanded. The aim of this study was to establish 12-month changes in the Upper Limb Module in a cohort of non-ambulant spinal muscular atrophy patients and their correlation with changes on the Hammersmith Functional Motor Scale Expanded. The Upper Limb Module scores ranged between 0 and 17 (mean 10.23, SD 4.81) at baseline and between 1 and 17 at 12 months (mean 10.27, SD 4.74). The Hammersmith Functional Motor Scale Expanded scores ranged between 0 and 34 (mean 12.43, SD 9.13) at baseline and between 0 and 34 at 12 months (mean 12.08, SD 9.21). The correlation betweeen the two scales was 0.65 at baseline and 0.72 on the 12 month changes. Our results confirm that the Upper Limb Module can capture functional changes in non-ambulant spinal muscular atrophy patients not otherwise captured by the other scale and that the combination of the two measures allows to capture changes in different subgroups of patients in whom baseline scores and functional changes may be influenced by several variables such as age. Copyright © 2014 Elsevier B.V. All rights reserved.

Subacute effects of cervicothoracic spinal thrust/non-thrust in addition to shoulder manual therapy plus exercise intervention in individuals with subacromial impingement syndrome: a prospective, randomized controlled clinical trial pilot study.

PubMed

Wright, Alexis A; Donaldson, Megan; Wassinger, Craig A; Emerson-Kavchak, Alicia J

2017-09-01

To determine the subacute effects of cervicothoracic spinal thrust/non-thrust in addition to shoulder non-thrust plus exercise in patients with subacromial pathology. This was a randomized, single blinded controlled trial pilot study. This trial was registered at ClinicalTrials.gov (NCT01753271) and reported according to Consolidated Standards of Reporting Trials requirements. Patients were randomly assigned to either shoulder treatment plus cervicothoracic spinal thrust/non-thrust or shoulder treatment-only group. Primary outcomes were average pain intensity (Numeric Pain Rating Scale) and physical function (Shoulder Pain and Disability Index) at 2 weeks, 4 weeks, and patient discharge. 18 patients, mean age 43.1(15.8) years satisfied the eligibility criteria and were analyzed for follow-up data. Both groups showed statistically significant improvements in both pain and function at 2 weeks, 4 weeks, and discharge. The between-group differences for changes in pain or physical function were not significant at any time point. The addition of cervicothoracic spinal thrust/non-thrust to the shoulder treatment-only group did not significantly alter improvement in pain or function in patients with subacromial pathology. Both approaches appeared to provide an equally notable benefit. Both groups improved on all outcomes and met the criteria for clinical relevance for both pain and function. 2b.

Investigation into an outbreak of encephalomyelitis caused by a neuroinvasive porcine sapelovirus in the United Kingdom.

PubMed

Schock, Alex; Gurrala, Rajesh; Fuller, Harriet; Foyle, Leo; Dauber, Malte; Martelli, Francesca; Scholes, Sandra; Roberts, Lisa; Steinbach, Falko; Dastjerdi, Akbar

2014-08-27

An outbreak of neurological disease in grower pigs characterised by ataxia and paraparesis was investigated in this study. The outbreak occurred 3-4 weeks post weaning in grower pigs which displayed signs of spinal cord damage progressing to recumbency. Pathology in the affected spinal cords and to a lesser extent in the brainstem was characterised by pronounced inflammation and neuronophagia in the grey matter. Molecular investigation using a pan-virus microarray identified a virus related to porcine sapelovirus (PSV) in the spinal cord of the two affected pigs examined. Analysis of 802 nucleotides of the virus polymerase gene showed the highest homology with those of viruses in the genus Sapelovirus of Picornaviridae. This PSV, strain G5, shared 91-93%, 67-69% and 63% nucleotide homology with porcine, simian and avian sapeloviruses, respectively. The nucleotide homology to other members of the Picornaviridae ranged from 41% to 62%. Furthermore, viral antigen was detected and co-localised in the spinal cord lesions of affected animals by an antibody known to react with PSV. In conclusion, clinical and laboratory observations of the diseased pigs in this outbreak are consistent with PSV-G5 being the causative agent. To the best of the authors' knowledge, this is the first unequivocal report of polioencephalomyelitis in pigs by a neuroinvasive PSV in the United Kingdom. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Core Self-Evaluations as Personal Factors in the World Health Organization's International Classification of Functioning, Disability and Health Model: An Application in Persons with Spinal Cord Injury

ERIC Educational Resources Information Center

Yaghmanian, Rana; Smedema, Susan Miller; Thompson, Kerry

2017-01-01

Purpose: To evaluate Chan, Gelman, Ditchman, Kim, and Chiu's (2009) revised World Health Organization's International Classification of Functioning, Disability and Health (ICF) model using core self-evaluations (CSE) to account for Personal Factors in persons with spinal cord injury (SCI). Method: One hundred eighty-seven adults with SCI were…

Pax2/8 act redundantly to specify glycinergic and GABAergic fates of multiple spinal interneurons

PubMed Central

Batista, Manuel F.; Lewis, Katharine E.

2008-01-01

The spinal cord contains several distinct classes of neurons but it is still unclear how many of the functional characteristics of these cells are specified. One of the most crucial functional characteristics of a neuron is its neurotransmitter fate. In this paper, we show that in zebrafish most glycinergic and many GABAergic spinal interneurons express Pax2a, Pax2b and Pax8 and that these transcription factors are redundantly required for the neurotransmitter fates of many of these cells. We also demonstrate that the function of these Pax2/8 transcription factors is very specific: in embryos in which Pax2a, Pax2b and Pax8 are simultaneously knocked-down, many neurons lose their glycinergic and/or GABAergic characteristics, but they do not become glutamatergic or cholinergic and their soma morphologies and axon trajectories are unchanged. In mouse, Pax2 is required for correct specification of GABAergic interneurons in the dorsal horn, but it is not required for the neurotransmitter fates of other Pax2-expressing spinal neurons. Our results suggest that this is probably due to redundancy with Pax8 and that the function of Pax2/8 in specifying GABAergic and glycinergic neuronal fates is much broader than was previously appreciated and is highly conserved between different vertebrates. PMID:18761336

Pax2/8 act redundantly to specify glycinergic and GABAergic fates of multiple spinal interneurons.

PubMed

Batista, Manuel F; Lewis, Katharine E

2008-11-01

The spinal cord contains several distinct classes of neurons but it is still unclear how many of the functional characteristics of these cells are specified. One of the most crucial functional characteristics of a neuron is its neurotransmitter fate. In this paper, we show that in zebrafish most glycinergic and many GABAergic spinal interneurons express Pax2a, Pax2b and Pax8 and that these transcription factors are redundantly required for the neurotransmitter fates of many of these cells. We also demonstrate that the function of these Pax2/8 transcription factors is very specific: in embryos in which Pax2a, Pax2b and Pax8 are simultaneously knocked-down, many neurons lose their glycinergic and/or GABAergic characteristics, but they do not become glutamatergic or cholinergic and their soma morphologies and axon trajectories are unchanged. In mouse, Pax2 is required for correct specification of GABAergic interneurons in the dorsal horn, but it is not required for the neurotransmitter fates of other Pax2-expressing spinal neurons. Our results suggest that this is probably due to redundancy with Pax8 and that the function of Pax2/8 in specifying GABAergic and glycinergic neuronal fates is much broader than was previously appreciated and is highly conserved between different vertebrates.

The human natural killer-1 (HNK-1) glycan mimetic ursolic acid promotes functional recovery after spinal cord injury in mouse.

PubMed

Sahu, Sudhanshu; Li, Rong; Kadeyala, Praveen Kumar; Liu, Shisong; Schachner, Melitta

2018-05-01

Human natural killer-1 (HNK-1) cell antigen is a glycan epitope involved in several neural events, such as neuritogenesis, myelination, synaptic plasticity and regeneration of the nervous system after injury. We have recently identified the small organic compound ursolic acid (UA) as a HNK-1 mimetic with the aim to test its therapeutic potential in the central nervous system. UA, a plant-derived pentacyclic triterpenoid, is well known for its multiple biological functions, including neuroprotective, antioxidant and anti-inflammatory activities. In the present study, we evaluated its functions in a mouse model of spinal cord injury (SCI) and explored the molecular mechanisms underlying its positive effects. Oral administration of UA to mice 1 h after SCI and thereafter once daily for 6 weeks enhanced the regaining of motor functions and axonal regrowth, and decreased astrogliosis. UA administration decreased levels of proinflammatory markers, including interleukin-6 and tumor necrosis factor-α, in the injured spinal cord at the acute phase of inflammation and activated the mitogen-activated protein kinase and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways in the injured spinal cord. Taken together, these results suggest that UA may be a candidate for treatment of nervous system injuries. Copyright © 2017. Published by Elsevier Inc.

The Extract of Roots of Sophora flavescens Enhances the Recovery of Motor Function by Axonal Growth in Mice with a Spinal Cord Injury

PubMed Central

Tanabe, Norio; Kuboyama, Tomoharu; Kazuma, Kohei; Konno, Katsuhiro; Tohda, Chihiro

2016-01-01

Although axonal extension to reconstruct spinal tracts should be effective for restoring function after spinal cord injury (SCI), chondroitin sulfate proteoglycan (CSPG) levels increase at spinal cord lesion sites, and inhibit axonal regrowth. In this study, we found that the water extract of roots of Sophora flavescens extended the axons of mouse cortical neurons, even on a CSPG-coated surface. Consecutive oral administrations of S. flavescens extract to SCI mice for 31 days increased the density of 5-HT-positive axons at the lesion site and improved the motor function. Further, the active constituents in the S. flavescens extract were identified. The water and alkaloid fractions of the S. flavescens extract each exhibited axonal extension activity in vitro. LC/MS analysis revealed that these fractions mainly contain matrine and/or oxymatrine, which are well-known major compounds in S. flavescens. Matrine and oxymatrine promoted axonal extension on the CSPG-coated surface. This study is the first to demonstrate that S. flavescens extract, matrine, and oxymatrine enhance axonal growth in vitro, even on a CSPG-coated surface, and that S. flavescens extract improves motor function and increases axonal density in SCI mice. PMID:26834638

The international spinal cord injury endocrine and metabolic function basic data set.

PubMed

Bauman, W A; Biering-Sørensen, F; Krassioukov, A

2011-10-01

To develop the International Spinal Cord Injury (SCI) Endocrine and Metabolic Function Basic Data Set within the framework of the International SCI Data Sets that would facilitate consistent collection and reporting of basic endocrine and metabolic findings in the SCI population. International. The International SCI Endocrine and Metabolic Function Data Set was developed by a working group. The initial data set document was revised on the basis of suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations and societies, and individual reviewers. In addition, the data set was posted for 2 months on ISCoS and ASIA websites for comments. The final International SCI Endocrine and Metabolic Function Data Set contains questions on the endocrine and metabolic conditions diagnosed before and after spinal cord lesion. If available, information collected before injury is to be obtained only once, whereas information after injury may be collected at any time. These data include information on diabetes mellitus, lipid disorders, osteoporosis, thyroid disease, adrenal disease, gonadal disease and pituitary disease. The question of gonadal status includes stage of sexual development and that for females also includes menopausal status. Data will be collected for body mass index and for the fasting serum lipid profile. The complete instructions for data collection and the data sheet itself are freely available on the websites of ISCoS (http://www.iscos.org.uk) and ASIA (http://www.asia-spinalinjury.org).

Adenovirus vector-mediated ex vivo gene transfer of brain-derived neurotrophic factor to bone marrow stromal cells promotes axonal regeneration after transplantation in completely transected adult rat spinal cord

PubMed Central

Kamada, Takahito; Hashimoto, Masayuki; Murakami, Masazumi; Shirasawa, Hiroshi; Sakao, Seiichiro; Ino, Hidetoshi; Yoshinaga, Katsunori; Koshizuka, Shuhei; Moriya, Hideshige; Yamazaki, Masashi

2007-01-01

The aim of this study was to evaluate the efficacy in adult rat completely transected spinal cord of adenovirus vector-mediated brain-derived neurotrophic factor (BDNF) ex vivo gene transfer to bone marrow stromal cells (BMSC). BMSC were infected with adenovirus vectors carrying β-galactosidase (AxCALacZ) or BDNF (AxCABDNF) genes. The T8 segment of spinal cord was removed and replaced by graft containing Matrigel alone (MG group) or Matrigel and BMSC infected by AxCALacZ (BMSC-LacZ group) or AxCABDNF (BMSC-BDNF group). Axons in the graft were evaluated by immunohistochemistry and functional recovery was assessed with BBB locomotor scale. In the BMSC-BDNF group, the number of fibers positive for growth associated protein-43, tyrosine hydroxylase, and calcitonin gene-related peptide was significantly larger than numbers found for the MG and BMSC-LacZ groups. Rats from BMSC-BDNF and BMSC-LacZ groups showed significant recovery of hind limb function compared with MG rats; however, there was no significant difference between groups in degree of functional recovery. These findings demonstrate that adenovirus vector-mediated ex vivo gene transfer of BDNF enhances the capacity of BMSC to promote axonal regeneration in this completely transected spinal cord model; however, BDNF failed to enhance hind limb functional recovery. Further investigation is needed to establish an optimal combination of cell therapy and neurotrophin gene transfer for cases of spinal cord injury. PMID:17885772

Paraplegic patients: how to measure balance and what is normal or functional?

PubMed

Barkoh, Kaku; Lucas, Joshua W; Lee, Larry; Hsieh, Patrick C; Wang, Jeffrey C; Rolfe, Kevin

2018-02-01

To review the current understanding and data of sagittal balance and alignment considerations in paraplegic patients. A PubMed literature search was conducted to identify all relevant articles relating to sagittal alignment and sagittal balance considerations in paraplegic and spinal cord injury patients. While there are numerous studies and publications on sagittal balance in the ambulatory patient with spinal deformity or complex spine disorders, there is paucity of the literature on "normal" sagittal balance in the paraplegic patients. Studies have reported significantly alterations of the sagittal alignment parameters in the non-ambulatory paraplegic patients compared to ambulatory patients. The variability of the alignment changes is related to the differences in the level of the spinal cord injury and their differences in the activations of truncal muscles to allow functional movements in those patients, particularly in optimizing sitting and transferring. Surgical goal in treating paraplegic patients with complex pathologies should not be solely directed to achieve the "normal" radiographic parameters of sagittal alignment in the ambulatory patients. The goal should be to maintain good coronal balance to allow ideal sitting position and to preserve motion segment to optimize functions of paraplegia patients. Current available literature data have not defined normal sagittal parameters for paraplegic patients. There are significant differences in postural sagittal parameters and muscle activations in paraplegic and non-spinal cord injury patients that can lead to differences in sagittal alignment and balance. Treatment goal in spine surgery for paraplegic patients should address their global function, sitting balance, and ability to perform self-care rather than the accepted radiographic parameters for adult spinal deformity in ambulatory patients.

Electronic bypass of spinal lesions: activation of lower motor neurons directly driven by cortical neural signals.

PubMed

Li, Yan; Alam, Monzurul; Guo, Shanshan; Ting, K H; He, Jufang

2014-07-03

Lower motor neurons in the spinal cord lose supraspinal inputs after complete spinal cord injury, leading to a loss of volitional control below the injury site. Extensive locomotor training with spinal cord stimulation can restore locomotion function after spinal cord injury in humans and animals. However, this locomotion is non-voluntary, meaning that subjects cannot control stimulation via their natural "intent". A recent study demonstrated an advanced system that triggers a stimulator using forelimb stepping electromyographic patterns to restore quadrupedal walking in rats with spinal cord transection. However, this indirect source of "intent" may mean that other non-stepping forelimb activities may false-trigger the spinal stimulator and thus produce unwanted hindlimb movements. We hypothesized that there are distinguishable neural activities in the primary motor cortex during treadmill walking, even after low-thoracic spinal transection in adult guinea pigs. We developed an electronic spinal bridge, called "Motolink", which detects these neural patterns and triggers a "spinal" stimulator for hindlimb movement. This hardware can be head-mounted or carried in a backpack. Neural data were processed in real-time and transmitted to a computer for analysis by an embedded processor. Off-line neural spike analysis was conducted to calculate and preset the spike threshold for "Motolink" hardware. We identified correlated activities of primary motor cortex neurons during treadmill walking of guinea pigs with spinal cord transection. These neural activities were used to predict the kinematic states of the animals. The appropriate selection of spike threshold value enabled the "Motolink" system to detect the neural "intent" of walking, which triggered electrical stimulation of the spinal cord and induced stepping-like hindlimb movements. We present a direct cortical "intent"-driven electronic spinal bridge to restore hindlimb locomotion after complete spinal cord injury.

International spinal cord injury male sexual function and female sexual and reproductive function basic data sets-version 2.0.

PubMed

Alexander, Marcalee S; New, Peter W; Biering-Sørensen, Fin; Courtois, Frederique; Popolo, Giulio Del; Elliott, Stacy; Kiekens, Carlotte; Vogel, Lawrence; Previnaire, Jean G

2017-01-01

Data set review and modification. To describe modifications in the International Spinal Cord Injury (SCI) Male Sexual Function Basic Data Set Version 2.0 and the International SCI Female Sexual and Reproductive Function Basic Data Set Version 2.0. International expert work group using on line communication. An international team of experts was compiled to review and revise the International SCI Male Sexual Function and Female Sexual and Reproductive Function Basic Data Sets Version 1.0. The group adapted Version 1.0 based upon review of published research, suggestions from concerned individuals and on line work group consensus. The revised data sets were then posted on the International Spinal Cord Society (ISCoS) and American Spinal Injury Association (ASIA) websites for 2 months for review. Subsequently, the data sets were approved by the ISCoS Scientific and Executive Committees and ASIA board of directors. The data sets were modified to a self-report format. They were reviewed for appropriateness for the pediatric age group and adapted to include a new variable to address the issue of sexual orientation. A clarification of the difference between the data sets and the autonomic standards was also developed. Sexuality is a continuously evolving topic. Modifications were needed to address this topic in a comprehensive fashion. It is recommended that Version 2.0 of these data sets are used for ongoing documentation of sexual status in the medical record and for documentation of sexual concerns during on-going research.

Overreaching in coordination dynamics therapy in an athlete with a spinal cord injury.

PubMed

Schalow, G; Vaher, I; Jaigma, P

2008-03-01

A motocross athlete suffered a clinically complete spinal cord injury (SCI) during competition. Although MRIs (magnetic resonance imaging) showed a complete spinal cord injury at the Thoracic 11/12 levels, surface EMG recordings indicated the survival of few tract fibres across the injury site. Six weeks after the accident the subject began intensive Coordination Dynamics Therapy (CDT) at an up-to-date therapy centre. The subject trained at his physical limits to induce structural and functional repair. Exercising at variable loads between 20 and 200N (on a special CDT and recording device) generated periods of overreaching and super-compensation. By plotting coordination dynamics values (kinesiology), including high-load exertion (200N) and hysteresis curves, periods of overreaching and super-compensation were made graphically visible. It was found that symmetrical improvements of central nervous system (CNS) functioning occurred during overreaching. Improvements in spinal cord functioning were achieved throughout one year of CDT in this chronically injured subject with an almost anatomically complete SCI. It is discussed that the measuring of CNS functions by means of recording coordination dynamics is a powerful and non-invasive tool ideal for exact quantitative and qualitative measurements of improvement (or change) in CNS functioning. Such diagnostics may be of particular importance in sport during training and before competition. Also, coordination dynamics might be used to measure the effects of prolonged exposure to reduced gravitational conditions on CNS functions, such as faced by astronauts.

Effects of core instability strength training on trunk muscle strength, spinal mobility, dynamic balance and functional mobility in older adults.

PubMed

Granacher, Urs; Lacroix, Andre; Muehlbauer, Thomas; Roettger, Katrin; Gollhofer, Albert

2013-01-01

Age-related postural misalignment, balance deficits and strength/power losses are associated with impaired functional mobility and an increased risk of falling in seniors. Core instability strength training (CIT) involves exercises that are challenging for both trunk muscles and postural control and may thus have the potential to induce benefits in trunk muscle strength, spinal mobility and balance performance. The objective was to investigate the effects of CIT on measures of trunk muscle strength, spinal mobility, dynamic balance and functional mobility in seniors. Thirty-two older adults were randomly assigned to an intervention group (INT; n = 16, aged 70.8 ± 4.1 years) that conducted a 9-week progressive CIT or to a control group (n = 16, aged 70.2 ± 4.5 years). Maximal isometric strength of the trunk flexors/extensors/lateral flexors (right, left)/rotators (right, left) as well as of spinal mobility in the sagittal and the coronal plane was measured before and after the intervention program. Dynamic balance (i.e. walking 10 m on an optoelectric walkway, the Functional Reach test) and functional mobility (Timed Up and Go test) were additionally tested. Program compliance was excellent with participants of the INT group completing 92% of the training sessions. Significant group × test interactions were found for the maximal isometric strength of the trunk flexors (34%, p < 0.001), extensors (21%, p < 0.001), lateral flexors (right: 48%, p < 0.001; left: 53%, p < 0.001) and left rotators (42%, p < 0.001) in favor of the INT group. Further, training-related improvements were found for spinal mobility in the sagittal (11%, p < 0.001) and coronal plane (11%, p = 0.06) directions, for stride velocity (9%, p < 0.05), the coefficient of variation in stride velocity (31%, p < 0.05), the Functional Reach test (20%, p < 0.05) and the Timed Up and Go test (4%, p < 0.05) in favor of the INT group. CIT proved to be a feasible exercise program for seniors with a high adherence rate. Age-related deficits in measures of trunk muscle strength, spinal mobility, dynamic balance and functional mobility can be mitigated by CIT. This training regimen could be used as an adjunct or even alternative to traditional balance and/or resistance training. Copyright © 2012 S. Karger AG, Basel.

The Lesioned Spinal Cord Is a “New” Spinal Cord: Evidence from Functional Changes after Spinal Injury in Lamprey

PubMed Central

Parker, David

2017-01-01

Finding a treatment for spinal cord injury (SCI) focuses on reconnecting the spinal cord by promoting regeneration across the lesion site. However, while regeneration is necessary for recovery, on its own it may not be sufficient. This presumably reflects the requirement for regenerated inputs to interact appropriately with the spinal cord, making sub-lesion network properties an additional influence on recovery. This review summarizes work we have done in the lamprey, a model system for SCI research. We have compared locomotor behavior (swimming) and the properties of descending inputs, locomotor networks, and sensory inputs in unlesioned animals and animals that have received complete spinal cord lesions. In the majority (∼90%) of animals swimming parameters after lesioning recovered to match those in unlesioned animals. Synaptic inputs from individual regenerated axons also matched the properties in unlesioned animals, although this was associated with changes in release parameters. This suggests against any compensation at these synapses for the reduced descending drive that will occur given that regeneration is always incomplete. Compensation instead seems to occur through diverse changes in cellular and synaptic properties in locomotor networks and proprioceptive systems below, but also above, the lesion site. Recovery of locomotor performance is thus not simply the reconnection of the two sides of the spinal cord, but reflects a distributed and varied range of spinal cord changes. While locomotor network changes are insufficient on their own for recovery, they may facilitate locomotor outputs by compensating for the reduction in descending drive. Potentiated sensory feedback may in turn be a necessary adaptation that monitors and adjusts the output from the “new” locomotor network. Rather than a single aspect, changes in different components of the motor system and their interactions may be needed after SCI. If these are general features, and where comparisons with mammalian systems can be made effects seem to be conserved, improving functional recovery in higher vertebrates will require interventions that generate the optimal spinal cord conditions conducive to recovery. The analyses needed to identify these conditions are difficult in the mammalian spinal cord, but lower vertebrate systems should help to identify the principles of the optimal spinal cord response to injury. PMID:29163065

SU-F-T-113: Inherent Functional Dependence of Spinal Cord Doses of Variable Irradiated Volumes in Spine SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, L; Braunstein, S; Chiu, J

2016-06-15

Purpose: Spinal cord tolerance for SBRT has been recommended for the maximum point dose level or at irradiated volumes such as 0.35 mL or 10% of contoured volumes. In this study, we investigated an inherent functional relationship that associates these dose surrogates for irradiated spinal cord volumes of up to 3.0 mL. Methods: A hidden variable termed as Effective Dose Radius (EDR) was formulated based on a dose fall-off model to correlate dose at irradiated spinal cord volumes ranging from 0 mL (point maximum) to 3.0 mL. A cohort of 15 spine SBRT cases was randomly selected to derive anmore » EDR-parameterized formula. The mean prescription dose for the studied cases was 21.0±8.0 Gy (range, 10–40Gy) delivered in 3±1 fractions with target volumes of 39.1 ± 70.6 mL. Linear regression and variance analysis were performed for the fitting parameters of variable EDR values. Results: No direct correlation was found between the dose at maximum point and doses at variable spinal cord volumes. For example, Pearson R{sup 2} = 0.643 and R{sup 2}= 0.491 were obtained when correlating the point maximum dose with the spinal cord dose at 1 mL and 3 mL, respectively. However, near perfect correlation (R{sup 2} ≥0.99) was obtained when corresponding parameterized EDRs. Specifically, Pearson R{sup 2}= 0.996 and R{sup 2} = 0.990 were obtained when correlating EDR (maximum point dose) with EDR (dose at 1 mL) and EDR(dose at 3 mL), respectively. As a result, high confidence level look-up tables were established to correlate spinal cord doses at the maximum point to any finite irradiated volumes. Conclusion: An inherent functional relationship was demonstrated for spine SBRT. Such a relationship unifies dose surrogates at variable cord volumes and proves that a single dose surrogate (e.g. point maximum dose) is mathematically sufficient in constraining the overall spinal cord dose tolerance for SBRT.« less

Assessment of physiological noise modelling methods for functional imaging of the spinal cord.

PubMed

Kong, Yazhuo; Jenkinson, Mark; Andersson, Jesper; Tracey, Irene; Brooks, Jonathan C W

2012-04-02

The spinal cord is the main pathway for information between the central and the peripheral nervous systems. Non-invasive functional MRI offers the possibility of studying spinal cord function and central sensitisation processes. However, imaging neural activity in the spinal cord is more difficult than in the brain. A significant challenge when dealing with such data is the influence of physiological noise (primarily cardiac and respiratory), and currently there is no standard approach to account for these effects. We have previously studied the various sources of physiological noise for spinal cord fMRI at 1.5T and proposed a physiological noise model (PNM) (Brooks et al., 2008). An alternative de-noising strategy, selective averaging filter (SAF), was proposed by Deckers et al. (2006). In this study we reviewed and implemented published physiological noise correction methods at higher field (3T) and aimed to find the optimal models for gradient-echo-based BOLD acquisitions. Two general techniques were compared: physiological noise model (PNM) and selective averaging filter (SAF), along with regressors designed to account for specific signal compartments and physiological processes: cerebrospinal fluid (CSF), motion correction (MC) parameters, heart rate (HR), respiration volume per time (RVT), and the associated cardiac and respiratory response functions. Functional responses were recorded from the cervical spinal cord of 18 healthy subjects in response to noxious thermal and non-noxious punctate stimulation. The various combinations of models and regressors were compared in three ways: the model fit residuals, regression model F-tests and the number of activated voxels. The PNM was found to outperform SAF in all three tests. Furthermore, inclusion of the CSF regressor was crucial as it explained a significant amount of signal variance in the cord and increased the number of active cord voxels. Whilst HR, RVT and MC explained additional signal (noise) variance, they were also found (in particular HR and RVT) to have a negative impact on the parameter estimates (of interest)--as they may be correlated with task conditions e.g. noxious thermal stimuli. Convolution with previously published cardiac and respiratory impulse response functions was not found to be beneficial. The other novel aspect of current study is the investigation of the influence of pre-whitening together with PNM regressors on spinal fMRI data. Pre-whitening was found to reduce non-white noise, which was not accounted for by physiological noise correction, and decrease false positive detection rates. Copyright © 2011 Elsevier Inc. All rights reserved.

Partial cure achieved in a patient with near-complete cervical spinal cord injury (95% injury) after 3 years of coordination dynamics therapy.

PubMed

Schalow, G

2009-01-01

This report describes a case of a now 20-year-old young lady with a severe spinal cord injury (SCI) at cervical 5/6 levels (ASIA A), in whom a repair of some spinal cord functions could be achieved within 3 years of optimal coordination dynamics therapy (CDT). Magnetic Resonance Imaging (MRI) showed a destruction of almost 95% of the cross-sectional area at the injury levels. The 5% (if at all) spared cord tissue most likely consisted of only sensory tracts, since no motor functions were preserved below the level of injury. A near-complete recovery of the important vegetative functions urinary bladder control, respiration, and vasomotor tone could be achieved. Her motor and sensory functions also improved to some extent, and she is off all medications. However, her motor recovery was limited and she is still wheel-chair-dependent. There is functional and structural (MRI) evidence that the human spinal cord regenerates upon CDT. The movement-based learning therapy included the training of supported crawling, up-righting, walking, running, jumping, balance training, and exercising on special CDT devices. The regeneration of the spinal cord started after more than one year of CDT, it was very limited but continuous, and gave rise to substantial functional recovery. The recovery induced by regeneration upon CDT was quantified in terms of transient increases of coordination dynamics values, the improvement of motor programs as assessed by surface electromyography (sEMG), the improvement of movement performances, and the increase of the spinal cord matter at the injury site, quantified by MRI. The similarity between the improvement at cellular and integrative (network) level during this regeneration and development is analyzed with respect to 'walking'. Comparing the effort, required to achieve substantial improvement in this case of severe cervical SCI (with 95% cord destruction; 5% spared tissue) with the effort required in the case of partial cervical SCI (50% destruction; 50% spared tissue), IT is noted that the 95% injury is 10 times more intractable. It is inferred that in severe SCI, the repair crucially depends on the percentage of the spared tissue (tracts fibres and neuronal networks) at the injury site. Improper handling of the patient therefore, as false transport or too late relief of spinal cord compression, may give rise to further mechanical damage of the cord tissue for which a later administered intensive cCDT cannot compensate for.

The Spinal Antinociceptive Effects of Endomorphins in Rats: Behavioral and G Protein Functional Studies

PubMed Central

Xie, Hong; Woods, James H.; Traynor, John R.; Ko, Mei-Chuan

2008-01-01

BACKGROUND Endomorphin-1 and endomorphin-2 are endogenous peptides that are highly selective for μ-opioid receptors. However, studies of their functional efficacy and selectivity are controversial. In this study, we systematically compared the effects of intrathecal (i.t.) administration of endomorphin-1 and -2 on nociception assays and G protein activation with those of [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), a highly effective peptidic μ-opioid receptor agonist. METHODS Male Sprague-Dawley rats were used. Acute and inflammatory pain models were used to compare the duration and magnitude of antinociception. Agonist-stimulated [35S]GTPγS binding was used to observe the functional activity at the level of the receptor-G protein in both spinal cord and thalamic membranes. In addition, antagonists selective for each receptor type were used to verify the functional selectivity of endomorphins in the rat spinal cord. RESULTS After i.t. administration, endomorphin-1 and -2 produced less antinociceptive effects than DAMGO in the model of acute pain. Concentration–response curves for DAMGO-, endomorphin-1-, and endomorphin-2-stimulated [35S]GTPγS binding revealed that both endomorphin-1 and -2 produced less G protein activation (i.e., approximately 50%–60%) than DAMGO did in the membranes of spinal cord and thalamus. In addition, i.t. endomorphin-induced antinociception was blocked by μ-opioid receptor selective dose of naltrexone (P < 0.05), but not by δ- and κ-opioid receptor antagonists, naltrindole and nor-binaltorphimine (P > 0.05). CONCLUSIONS Endomorphins are partial agonists for G protein activation at spinal and thalamic μ-opioid receptors. Both in vivo and in vitro measurements together suggest that DAMGO is more effective than endomorphins. Spinal endomorphins’ antinociceptive efficacy may range between 53% and 84% depending on the intensity and modality of the nociceptive stimulus. PMID:18499626

Effect of Surgical Approach on Pulmonary Function in Adolescent Idiopathic Scoliosis Patients: A Systemic Review and Meta-analysis.

PubMed

Lee, Andy C H; Feger, Mark A; Singla, Anuj; Abel, Mark F

2016-11-15

Systemic review and meta-analysis. To analyze the effect of spinal fusion and instrumentation for adolescent idiopathic scoliosis (AIS) on absolute pulmonary function test (PFTs). Pulmonary function is correlated with severity of deformity in AIS patients and studies that have analyzed the effect of spinal fusion and instrumentation on PFTs for AIS have reported inconsistent results. There is a need to analyze the effect of spinal fusion on PFTs with stratification by surgical approach. Our analysis included 22 studies. Cohen's d effect sizes were calculated for absolute PFT outcome measures with 95% confidence intervals (CI). Meta-analyses were performed at each postoperative time frame for six homogeneous surgical approaches: (i) combined anterior release and posterior fusion with instrumentation; (ii) combined video assisted anterior release and posterior fusion with instrumentation without thoracoplasty; (iii) posterior fusion with instrumentation without thoracoplasty; (iv) anterior fusion with instrumentation and without thoracoplasty; (v) video assisted anterior fusion with instrumentation without thoracoplasty; and (vi) any scoliosis surgery with additional thoracoplasty. Anterior spinal fusion with instrumentation, any scoliosis surgery with concomitant thoracoplasty, or video-assisted anterior fusion with instrumentation for AIS had similar absolute PFTs at their 2 year postoperative follow up compared with their preoperative PFTs (effect sizes ranging from -0.2-0.2 with all CI crossing "0"). Posterior spinal fusion with instrumentation (with or without an anterior release) demonstrated small to moderate increases in PFTs 2 years postoperatively (effect sizes ranging from 0.35-0.65 with all CI not crossing "0"). Anterior fusion with instrumentation, regardless of the approach, and any scoliosis surgery with concomitant thoracoplasty do not lead to significant change in pulmonary functions 2 year after surgery. Posterior spinal fusion with instrumentation (with or without an anterior release) resulted in small to moderate increases in PFTs. N/A.

Integration of donor mesenchymal stem cell-derived neuron-like cells into host neural network after rat spinal cord transection.

PubMed

Zeng, Xiang; Qiu, Xue-Cheng; Ma, Yuan-Huan; Duan, Jing-Jing; Chen, Yuan-Feng; Gu, Huai-Yu; Wang, Jun-Mei; Ling, Eng-Ang; Wu, Jin-Lang; Wu, Wutian; Zeng, Yuan-Shan

2015-06-01

Functional deficits following spinal cord injury (SCI) primarily attribute to loss of neural connectivity. We therefore tested if novel tissue engineering approaches could enable neural network repair that facilitates functional recovery after spinal cord transection (SCT). Rat bone marrow-derived mesenchymal stem cells (MSCs), genetically engineered to overexpress TrkC, receptor of neurotrophin-3 (NT-3), were pre-differentiated into cells carrying neuronal features via co-culture with NT-3 overproducing Schwann cells in 3-dimensional gelatin sponge (GS) scaffold for 14 days in vitro. Intra-GS formation of MSC assemblies emulating neural network (MSC-GS) were verified morphologically via electron microscopy (EM) and functionally by whole-cell patch clamp recording of spontaneous post-synaptic currents. The differentiated MSCs still partially maintained prototypic property with the expression of some mesodermal cytokines. MSC-GS or GS was then grafted acutely into a 2 mm-wide transection gap in the T9-T10 spinal cord segments of adult rats. Eight weeks later, hindlimb function of the MSC-GS-treated SCT rats was significantly improved relative to controls receiving the GS or lesion only as indicated by BBB score. The MSC-GS transplantation also significantly recovered cortical motor evoked potential (CMEP). Histologically, MSC-derived neuron-like cells maintained their synapse-like structures in vivo; they additionally formed similar connections with host neurites (i.e., mostly serotonergic fibers plus a few corticospinal axons; validated by double-labeled immuno-EM). Moreover, motor cortex electrical stimulation triggered c-fos expression in the grafted and lumbar spinal cord cells of the treated rats only. Our data suggest that MSC-derived neuron-like cells resulting from NT-3-TrkC-induced differentiation can partially integrate into transected spinal cord and this strategy should be further investigated for reconstructing disrupted neural circuits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regeneration of Xenopus laevis spinal cord requires Sox2/3 expressing cells

PubMed Central

Muñoz, Rosana; Edwards-Faret, Gabriela; Moreno, Mauricio; Zuñiga, Nikole; Cline, Hollis; Larraín, Juan

2016-01-01

Spinal cord regeneration is very inefficient in humans, causing paraplegia and quadriplegia. Studying model organisms that can regenerate the spinal cord in response to injury could be useful for understanding the cellular and molecular mechanisms that explain why this process fails in humans. Here, we use Xenopus laevis as a model organism to study spinal cord repair. Histological and functional analyses showed that larvae at pre-metamorphic stages restore anatomical continuity of the spinal cord and recover swimming after complete spinal cord transection. These regenerative capabilities decrease with onset of metamorphosis. The ability to study regenerative and non-regenerative stages in Xenopus laevis makes it a unique model system to study regeneration. We studied the response of Sox2/3 expressing cells to spinal cord injury and their function in the regenerative process. We found that cells expressing Sox2 and/or Sox3 are present in the ventricular zone of regenerative animals and decrease in non-regenerative froglets. Bromodeoxyuridine (BrdU) experiments and in vivo time-lapse imaging studies using green fluorescent protein (GFP) expression driven by the Sox3 promoter showed a rapid, transient and massive proliferation of Sox2/3+ cells in response to injury in the regenerative stages. The in vivo imaging also demonstrated that Sox2/3+ neural progenitor cells generate neurons in response to injury. In contrast, these cells showed a delayed and very limited response in non-regenerative froglets. Sox2 knockdown and overexpression of a dominant negative form of Sox2 disrupts locomotor and anatomical-histological recovery. We also found that neurogenesis markers increase in response to injury in regenerative but not in non-regenerative animals. We conclude that Sox2 is necessary for spinal cord regeneration and suggest a model whereby spinal cord injury activates proliferation of Sox2/3 expressing cells and their differentiation into neurons, a mechanism that is lost in non-regenerative froglets. PMID:25797152

Development of a comprehensive survey of sexuality issues including a self-report version of the International Spinal Cord Injury sexual function basic data sets.

PubMed

New, P W; Currie, K E

2016-08-01

Questionnaire development, validation and completion. Develop comprehensive survey of sexuality issues including validated self-report versions of the International Spinal Cord Injury male sexual function and female sexual and reproductive function basic data sets (SR-iSCI-sexual function). People with spinal cord damage (SCD) living in the community, Australia from August 2013 to June 2014. An iterative process involving rehabilitation medicine clinicians, a nurse specialising in sexuality issues in SCD and people with SCD who developed a comprehensive survey that included the SR-iSCI-sexual function. Participants recruitment through spinal rehabilitation review clinic and community organisations that support people with SCD. Surveys completed by 154 people. Most were male (n=101, 65.6%). Respondents' median age was 50 years (interquartile range (IQR) 38-58), and they were a median of 10 years (IQR 4-20) after the onset of SCD. Sexual problems unrelated to SCD were reported by 12 (8%) respondents, and 114 (n=75.5%) reported sexual problems because of SCD. Orgasms were much less likely (χ(2)=13.1, P=0.006) to be normal in males (n=5, 5%) compared with females (n=11, 22%). Males had significantly worse (χ(2)=26.0, P=0.001) psychogenic genital functioning (normal n=9, 9%) than females (normal n=13, 26%) and worse (χ(2)=10.8, P=0.013) reflex genital functioning. Normal ejaculation was reported in only three (3%) men. Most (n=26, 52%) women reported reduced or absent menstruation pattern since SCD. The SR-iSCI-sexual function provides a useful tool for researchers and clinicians to collect information regarding patient-reported sexual functioning after SCD and to facilitate comparative studies.

A new method to approximate load-displacement relationships of spinal motion segments for patient-specific multi-body models of scoliotic spine.

PubMed

Jalalian, Athena; Tay, Francis E H; Arastehfar, Soheil; Liu, Gabriel

2017-06-01

Load-displacement relationships of spinal motion segments are crucial factors in characterizing the stiffness of scoliotic spine models to mimic the spine responses to loads. Although nonlinear approach to approximation of the relationships can be superior to linear ones, little mention has been made to deriving personalized nonlinear load-displacement relationships in previous studies. A method is developed for nonlinear approximation of load-displacement relationships of spinal motion segments to assist characterizing in vivo the stiffness of spine models. We propose approximation by tangent functions and focus on rotational displacements in lateral direction. The tangent functions are characterized using lateral bending test. A multi-body model was characterized to 18 patients and utilized to simulate four spine positions; right bending, left bending, neutral, and traction. The same was done using linear functions to assess the performance of the proposed tangent function in comparison with the linear function. Root-mean-square error (RMSE) of the displacements estimated by the tangent functions was 44 % smaller than the linear functions. This shows the ability of our tangent function in approximation of the relationships for a range of infinitesimal to large displacements involved in the spine movement to the four positions. In addition, the models based on the tangent functions yielded 67, 55, and 39 % smaller RMSEs of Ferguson angles, locations of vertebrae, and orientations of vertebrae, respectively, implying better estimates of spine responses to loads. Overall, it can be concluded that our method for approximating load-displacement relationships of spinal motion segments can offer good estimates of scoliotic spine stiffness.

Parasitic twin--a supernumerary limb associated with spinal malformations. A case report.

PubMed

Sahlu, Abat; Mesfin, Brook; Tirsit, Abenezer; Debebe, Tequam; Wester, Knut

2016-03-01

We describe a case of rachipagus parasitic twin with spinal cord malformations (lipomyelomeningocele and tethered cord) in a 7-month-old Ethiopian infant. The parasitic mass had a well-formed foot, ankle and lower leg and a small sinus that resembled an anus. Magnetic resonance imaging scans revealed spinal malformations including a distal syringohydromyelia. The mass was successfully resected and the dural attachment was closed. Histopathological examination confirmed the diagnosis. Postoperatively, the child had unchanged, intact neurological function in both lower limbs. Almost all rachipagus parasitic twins are associated with spinal malformations. They should, therefore, be operated on by surgeons experienced in myelomeningocele surgery.

North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord Injury: A Consortium of Military, Veterans Administration, and Civilian Hospitals

DTIC Science & Technology

2011-01-31

of the patient on arrival and includes a clinical evaluation, 5 measurement of state of consciousness with the Glasgow Coma Scale (GCS) and of...associated injuries with the Abbreviated Injury Scale . The American Spinal Injury Association impairment scale (AIS) is scored on admission and at key...the AIS Impairment Scale , and where appropriate, the Functional Independence Measure FIM™, the Spinal Cord Independence Measure (SCIM), and the

Sexual reflexes in male and female rats.

PubMed

Chung, S K; McVary, K T; McKenna, K E

1988-12-05

A novel preparation for the study of male and female sexual function in anesthetized, acutely spinalized rats is reported. In both sexes, the coitus reflex (the neuromuscular concomitants of sexual climax) could be elicited by mechanical stimulation of the distal urethra. It is concluded that the spinal sexual circuitry is essentially similar in both sexes and that the coitus reflex is generated by a hormone-insensitive spinal pattern generator and is triggered by a simple peripheral stimulus.

Treatment of spinal fractures with paraplegia.

PubMed

Riska, E B; Myllynen, P

1981-01-01

Of 206 patients with vertebral fractures in the thoraco-lumbar spine with spinal cord injuries, an antero-lateral decompression with stabilization of the injured segment of the vertebral column was undertaken in 56 cases. In all these cases there was a compression of the spinal cord from the front. 8 patients made a complete recovery, 31 a good recovery, and 6 were improved. In 8 patients no improvement was noted. 2 patients developed pressure sores later and 1 patient died one year after the operation of uraemia. 22 patients out of 55 got a normal function of the bladder and 25 patients out of 54 a normal function of the anal sphincter. 16 patients out of 17 made a complete or good recovery after removal of a displaced rotated vertebral bony fragment from the spinal canal, and 7 patients out of 9 with wedge shaped fractures. In our clinic today, in cases of vertebral fractures with neural involvement, reduction and internal fixation with Harrington rods and fusion of the injured segment is undertaken as soon as possible, also during the night. If narrowing of the neural canal and compression of the spinal cord are verified, a decompression operation with interbody fusion is undertaken during the next days.

Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.

PubMed

Sabino, Luzzi; Maria, Crovace Alberto; Luca, Lacitignola; Valerio, Valentini; Edda, Francioso; Giacomo, Rossi; Gloria, Invernici; Juan, Galzio Renato; Antonio, Crovace

2018-01-01

Proof of the efficacy and safety of a xenogeneic mesenchymal stem cell (MSCs) transplant for spinal cord injury (SCI) may theoretically widen the spectrum of possible grafts for neuroregeneration. Twenty rats were submitted to complete spinal cord transection. Ovine bone marrow MSCs, retrovirally transfected with red fluorescent protein and not previously induced for neuroglial differentiation, were applied in 10 study rats (MSCG). Fibrin glue was injected in 10 control rats (FGG). All rats were evaluated on a weekly basis and scored using the Basso-Beattie-Bresnahan (BBB) locomotor scale for 10 weeks, when the collected data were statistically analyzed. The spinal cords were then harvested and analyzed with light microscopy, immunohistochemistry, and immunofluorescence. Ovine MSCs culture showed positivity for Nestin. MSCG had a significant and durable recovery of motor functions ( P <.001). Red fluorescence was found at the injury sites in MSCG. Positivity for Nestin, tubulin βIII, NG2 glia, neuron-specific enolase, vimentin, and 200 kD neurofilament were also found at the same sites. Xenogeneic ovine bone marrow MSCs proved capable of engrafting into the injured rat spinal cord. Transdifferentiation into a neuroglial phenotype was able to support partial functional recovery.

Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats

PubMed Central

Sabino, Luzzi; Maria, Crovace Alberto; Luca, Lacitignola; Valerio, Valentini; Edda, Francioso; Giacomo, Rossi; Gloria, Invernici; Juan, Galzio Renato; Antonio, Crovace

2018-01-01

Background: Proof of the efficacy and safety of a xenogeneic mesenchymal stem cell (MSCs) transplant for spinal cord injury (SCI) may theoretically widen the spectrum of possible grafts for neuroregeneration. Methods: Twenty rats were submitted to complete spinal cord transection. Ovine bone marrow MSCs, retrovirally transfected with red fluorescent protein and not previously induced for neuroglial differentiation, were applied in 10 study rats (MSCG). Fibrin glue was injected in 10 control rats (FGG). All rats were evaluated on a weekly basis and scored using the Basso–Beattie–Bresnahan (BBB) locomotor scale for 10 weeks, when the collected data were statistically analyzed. The spinal cords were then harvested and analyzed with light microscopy, immunohistochemistry, and immunofluorescence. Results: Ovine MSCs culture showed positivity for Nestin. MSCG had a significant and durable recovery of motor functions (P <.001). Red fluorescence was found at the injury sites in MSCG. Positivity for Nestin, tubulin βIII, NG2 glia, neuron-specific enolase, vimentin, and 200 kD neurofilament were also found at the same sites. Conclusions: Xenogeneic ovine bone marrow MSCs proved capable of engrafting into the injured rat spinal cord. Transdifferentiation into a neuroglial phenotype was able to support partial functional recovery. PMID:29497572

Ex Vivo Diffusion Tensor Imaging of Spinal Cord Injury in Rats of Varying Degrees of Severity

PubMed Central

Jirjis, Michael B.; Kurpad, Shekar N.

2013-01-01

Abstract The aim of this study was to characterize magnetic resonance diffusion tensor imaging (DTI) in proximal regions of the spinal cord following a thoracic spinal cord injury (SCI). Sprague–Dawley rats (n=40) were administered a control, mild, moderate, or severe contusion injury at the T8 vertebral level. Six direction diffusion weighted images (DWIs) were collected ex vivo along the length of the spinal cord, with an echo/repetition time of 31.6 ms/14 sec and b=500 sec/mm2. Diffusion metrics were correlated to hindlimb motor function. Significant differences were found for whole cord region of interest (ROI) drawings for fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusion coefficient (LD), and radial diffusion coefficient (RD) at each of the cervical levels (p<0.01). Motor function correlated with MD in the cervical segments of the spinal cord (r2=0.80). The diffusivity of water significantly decreased throughout “uninjured” portions of the spinal cord following a contusion injury (p<0.05). Diffusivity metrics were found to be altered following SCI in both white and gray matter regions. Injury severity was associated with diffusion changes over the entire length of the cord. This study demonstrates that DTI is sensitive to SCI in regions remote from injury, suggesting that the diffusion metrics may be used as a biomarker for severity of injury. PMID:23782233

The Effects of Intraspinal Microstimulation on Spinal Cord Tissue in the Rat

PubMed Central

Bamford, Jeremy A.; Todd, Kathryn G.; Mushahwar, Vivian K.

2010-01-01

Intraspinal microstimulation (ISMS) involves the implantation of microwires into the spinal cord below the level of an injury to excite neural networks involved in the control of locomotion in the lower limbs. The goal of this study was to examine the potential spinal cord damage that might occur with chronic ISMS. We employed functional measures of force recruitment and immunohistochemical processing of serial spinal cord sections to evaluate any damage induced by spinal transection, implantation of ISMS arrays, and electrical stimulation of 4 hours/day for 30 days. Functional measurements showed no change in force recruitment following transection and chronic ISMS, indicating no changes to underlying neural networks. The implantation of sham intraspinal microwires produced a spatially-limited increase in the density of microglia/macrophages and GFAP+ astrocytes adjacent to the microwire tracks, indicating a persistent immune response. Most importantly, these results were not different from those around microwires that were chronically pulsed with charge levels up to 48 nC/phase. Likewise, measurements of neuronal density indicated no decrease in neuronal cell bodies in the ventral grey matter surrounding ISMS microwires (243.6/mm2 ± 35.3/mm2) compared to tissue surrounding sham microwires (207.8/mm2 ± 38.8/mm2). We conclude that the implantation of intraspinal microwires and chronic application of ISMS are well tolerated by spinal cord tissue. PMID:20430436

Sustained delivery of bioactive neurotrophin-3 to the injured spinal cord.

PubMed

Elliott Donaghue, Irja; Tator, Charles H; Shoichet, Molly S

2015-01-01

Spinal cord injury is a debilitating condition that currently lacks effective clinical treatment. Neurotrophin-3 (NT-3) has been demonstrated in experimental animal models to induce axonal regeneration and functional improvements, yet its local delivery remains challenging. For ultimate clinical translation, a drug delivery system is required for localized, sustained, and minimally invasive release. Here, an injectable composite drug delivery system (DDS) composed of biodegradable polymeric nanoparticles dispersed in a hyaluronan/methyl cellulose hydrogel was injected into the intrathecal space to achieve acute local delivery to the spinal cord after a thoracic clip compression injury. NT-3 was encapsulated in the DDS and released in vitro for up to 50 d. With a single injection of the DDS into the intrathecal space of the injured spinal cord, NT-3 diffused ventrally through the cord and was detectable in the spinal cord for at least 28 d therein. Delivery of NT-3 resulted in significant axon growth with no effect on the astroglial response to injury in comparison with vehicle and injury controls. NT-3 treatment promoted functional improvements at 21 d according to the Basso Beattie Bresnahan locomotor scale in comparison with the DDS alone. The sustained delivery of bioactive NT-3 to the injured spinal cord achieved in this study demonstrates the promise of this DDS for central nervous system repair.

Recovery of TES-MEPs during surgical decompression of the spine: a case series of eight patients.

PubMed

Visser, Jetze; Verra, Wiebe C; Kuijlen, Jos M; Horsting, Philip P; Journée, Henricus L

2014-12-01

This study aimed to illustrate the recovery of transcranial electrical stimulation motor evoked potentials during surgical decompression of the spinal cord in patients with impaired motor function preoperatively. Specific attention was paid to the duration of neurologic symptoms before surgery and the postoperative clinical recovery. A case series of eight patients was selected from a cohort of 74 patients that underwent spine surgery. The selected patients initially had low or absent transcranial electrical stimulation motor evoked potentials followed by a significant increase after surgical decompression of the spinal cord. A significant intraoperative increase in amplitude of motor evoked potentials was detected after decompression of the spinal cord or cauda equina in patients suffering from spinal canal stenosis (n = 2), extradural meningioma (n = 3), or a herniated nucleus polposus (n = 3). This was related to an enhanced neurologic outcome only if patients (n = 6) had a short onset (less than ½ year) of neurologic impairment before surgery. In patients with a short onset of neurologic impairment because of compression of the spinal cord or caudal fibers, an intraoperative recovery of transcranial electrical stimulation motor evoked potentials can indicate an improvement of motor function postoperatively. Therefore, transcranial electrical stimulation motor evoked potentials can be considered as a useful tool to the surgeon to monitor the quality of decompression of the spinal cord.

Evaluating diagnosis-based risk-adjustment methods in a population with spinal cord dysfunction.

PubMed

Warner, Grace; Hoenig, Helen; Montez, Maria; Wang, Fei; Rosen, Amy

2004-02-01

To examine performance of models in predicting health care utilization for individuals with spinal cord dysfunction. Regression models compared 2 diagnosis-based risk-adjustment methods, the adjusted clinical groups (ACGs) and diagnostic cost groups (DCGs). To improve prediction, we added to our model: (1) spinal cord dysfunction-specific diagnostic information, (2) limitations in self-care function, and (3) both 1 and 2. Models were replicated in 3 populations. Samples from 3 populations: (1) 40% of veterans using Veterans Health Administration services in fiscal year 1997 (FY97) (N=1,046,803), (2) veteran sample with spinal cord dysfunction identified by codes from the International Statistical Classification of Diseases, 9th Revision, Clinical Modifications (N=7666), and (3) veteran sample identified in Veterans Affairs Spinal Cord Dysfunction Registry (N=5888). Not applicable. Inpatient, outpatient, and total days of care in FY97. The DCG models (R(2) range,.22-.38) performed better than ACG models (R(2) range,.04-.34) for all outcomes. Spinal cord dysfunction-specific diagnostic information improved prediction more in the ACG model than in the DCG model (R(2) range for ACG,.14-.34; R(2) range for DCG,.24-.38). Information on self-care function slightly improved performance (R(2) range increased from 0 to.04). The DCG risk-adjustment models predicted health care utilization better than ACG models. ACG model prediction was improved by adding information.

“No Clinical Puzzles More Interesting”: Harvey Cushing and Spinal Trauma, The Johns Hopkins Hospital 1896-1912

PubMed Central

Dasenbrock, Hormuzdiyar H.; Pendleton, Courtney; Cohen-Gadol, Aaron A.; Witham, Timothy F.; Gokaslan, Ziya L.; Quinones-Hinojosa, Alfredo; Bydon, Ali

2015-01-01

Although Harvey Cushing played a central role in the establishment of neurosurgery in the United States, his work on the spine remains largely unknown. This article is not only the first time that Cushing's spinal cases while he was at Johns Hopkins have been reported, but also the first time his management of spinal trauma has been described. We report on 12 patients that Cushing treated from 1898 to 1911 who have never been reported before, including blunt and penetrating injuries, complete and incomplete spinal cord lesions, and both immediate and delayed presentations. Cushing performed laminectomies within 24 hours on patients with immediate presentations—both complete and incomplete spinal cord lesions. Among those with delayed presentations, Cushing did laminectomies on patients with incomplete spinal cord injuries. By the end of his tenure at Hopkins, Cushing advocated nonoperative treatment for all patients with complete spinal cord lesions. Four patients died while an inpatient, with meningitis and cystitis leading to the death of 1 and 3 patients, respectively. Cystitis was treated with intravesicular irrigation; an indwelling catheter was placed by a suprapubic cystostomy in four. Cushing was one of the first to report the use of x-ray in a spine patient, in a case that may have been one factor leading to his interest in the nervous system; Cushing also routinely obtained radiographs in those with spinal trauma. These cases illustrate Cushing's dedication to and rapport with his patients, even in the face of a dismal prognosis. PMID:21135734

Restoring voluntary grasping function in individuals with incomplete chronic spinal cord injury: pilot study.

PubMed

Kapadia, Naaz; Zivanovic, Vera; Popovic, Milos R

2013-01-01

Functional electrical stimulation (FES) therapy has been shown to be one of the most promising approaches for improving voluntary grasping function in individuals with subacute cervical spinal cord injury (SCI). To determine the effectiveness of FES therapy, as compared to conventional occupational therapy (COT), in improving voluntary hand function in individuals with chronic (≥24 months post injury), incomplete (American Spinal Injury Association Impairment Scale [AIS] B-D), C4 to C7 SCI. Eight participants were randomized to the intervention group (FES therapy; n = 5) or the control group (COT; n = 3). Both groups received 39 hours of therapy over 13 to 16 weeks. The primary outcome measure was the Toronto Rehabilitation Institute-Hand Function Test (TRI-HFT), and the secondary outcome measures were Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP), Functional Independence Measure (FIM) self-care subscore, and Spinal Cord Independence Measure (SCIM) self-care subscore. Outcome assessments were performed at baseline, after 39 sessions of therapy, and at 6 months following the baseline assessment. After 39 sessions of therapy, the intervention group improved by 5.8 points on the TRI-HFT's Object Manipulation Task, whereas the control group changed by only 1.17 points. Similarly, after 39 sessions of therapy, the intervention group improved by 4.6 points on the FIM self-care subscore, whereas the control group did not change at all. The results of the pilot data justify a clinical trial to compare FES therapy and COT alone to improve voluntary hand function in individuals with chronic incomplete tetraplegia.

Factors Affecting the Occurrence of Spinal Reflexes in Brain Dead Cases.

PubMed

Hosseini, Mahsa Sadat; Ghorbani, Fariba; Ghobadi, Omid; Najafizadeh, Katayoun

2015-08-01

Brain death is defined as the permanent absence of all cortical and brain stem reflexes. A wide range of spontaneous or reflex movements that are considered medullary reflexes are observed in heart beating cases that appear brain dead, which may create uncertainty about the diagnosis of brain death and cause delays in deceased-donor organ donation process. We determined the frequency and type of medullary reflexes and factors affecting their occurrence in brain dead cases. During 1 year, 122 cases who fulfilled the criteria for brain death were admitted to the special intensive care unit for organ procurement of Masih Daneshvari Hospital. Presence of spinal reflexes was evaluated by trained coordinators and was recorded in a form in addition to other information including demographic characteristics, cause of brain death, time from detection of brain death, history of craniotomy, vital signs, serum electrolyte levels, and parameters of arterial blood gas determination. Most cases (63%) included in this study were male, and mean age was 33 ± 15 y. There was > 1 spinal reflex observed in 40 cases (33%). The most frequent reflex was plantar response (17%) following by myoclonus (10%), triple flexion reflex (9%), pronator extension reflex (8%), and undulating toe reflex (7%). Mean systolic blood pressure was significantly higher in cases who exhibited medullary reflexes than other cases (126 ± 19 mm Hg vs 116 ± 17 mm Hg; P = .007). Spinal reflexes occur frequently in brain dead cases, especially when they become hemodynamically stable after treatment in the organ procurement unit. Observing these movements by caregivers and family members has a negative effect on obtaining family consent and organ donation. Increasing awareness about spinal reflexes is necessary to avoid suspicion about the brain death diagnosis and delays in organ donation.

Driving Safety after Spinal Surgery: A Systematic Review

PubMed Central

Alkhalili, Kenan; Hannallah, Jack; Ibeche, Bashar; Bajammal, Sohail; Baco, Abdul Moeen

2017-01-01

This study aimed to assess driving reaction times (DRTs) after spinal surgery to establish a timeframe for safe resumption of driving by the patient postoperatively. The MEDLINE and Google Scholar databases were analyzed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) Statement for clinical studies that investigated changes in DRTs following cervical and lumbar spinal surgery. Changes in DRTs and patients' clinical presentation, pathology, anatomical level affected, number of spinal levels involved, type of intervention, pain level, and driving skills were assessed. The literature search identified 12 studies that investigated postoperative DRTs. Six studies met the inclusion criteria; five studies assessed changes in DRT after lumbar spine surgery and two studies after cervical spina surgery. The spinal procedures were selective nerve root block, anterior cervical discectomy and fusion, and lumbar fusion and/ordecompression. DRTs exhibited variable responses to spinal surgery and depended on the patients' clinical presentation, spinal level involved, and type of procedure performed. The evidence regarding the patients' ability to resume safe driving after spinal surgery is scarce. Normalization of DRT or a return of DRT to pre-spinal intervention level is a widely accepted indicator for safe driving, with variable levels of statistical significance owing to multiple confounding factors. Considerations of the type of spinal intervention, pain level, opioid consumption, and cognitive function should be factored in the assessment of a patient's ability to safely resume driving. PMID:28443178

Driving Safety after Spinal Surgery: A Systematic Review.

PubMed

Alhammoud, Abduljabbar; Alkhalili, Kenan; Hannallah, Jack; Ibeche, Bashar; Bajammal, Sohail; Baco, Abdul Moeen

2017-04-01

This study aimed to assess driving reaction times (DRTs) after spinal surgery to establish a timeframe for safe resumption of driving by the patient postoperatively. The MEDLINE and Google Scholar databases were analyzed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) Statement for clinical studies that investigated changes in DRTs following cervical and lumbar spinal surgery. Changes in DRTs and patients' clinical presentation, pathology, anatomical level affected, number of spinal levels involved, type of intervention, pain level, and driving skills were assessed. The literature search identified 12 studies that investigated postoperative DRTs. Six studies met the inclusion criteria; five studies assessed changes in DRT after lumbar spine surgery and two studies after cervical spina surgery. The spinal procedures were selective nerve root block, anterior cervical discectomy and fusion, and lumbar fusion and/ordecompression. DRTs exhibited variable responses to spinal surgery and depended on the patients' clinical presentation, spinal level involved, and type of procedure performed. The evidence regarding the patients' ability to resume safe driving after spinal surgery is scarce. Normalization of DRT or a return of DRT to pre-spinal intervention level is a widely accepted indicator for safe driving, with variable levels of statistical significance owing to multiple confounding factors. Considerations of the type of spinal intervention, pain level, opioid consumption, and cognitive function should be factored in the assessment of a patient's ability to safely resume driving.

Geometric Structure of 3D Spinal Curves: Plane Regions and Connecting Zones

PubMed Central

Berthonnaud, E.; Hilmi, R.; Dimnet, J.

2012-01-01

This paper presents a new study of the geometric structure of 3D spinal curves. The spine is considered as an heterogeneous beam, compound of vertebrae and intervertebral discs. The spine is modeled as a deformable wire along which vertebrae are beads rotating about the wire. 3D spinal curves are compound of plane regions connected together by zones of transition. The 3D spinal curve is uniquely flexed along the plane regions. The angular offsets between adjacent regions are concentrated at level of the middle zones of transition, so illustrating the heterogeneity of the spinal geometric structure. The plane regions along the 3D spinal curve must satisfy two criteria: (i) a criterion of minimum distance between the curve and the regional plane and (ii) a criterion controlling that the curve is continuously plane at the level of the region. The geometric structure of each 3D spinal curve is characterized by the sizes and orientations of regional planes, by the parameters representing flexed regions and by the sizes and functions of zones of transition. Spinal curves of asymptomatic subjects show three plane regions corresponding to spinal curvatures: lumbar, thoracic and cervical curvatures. In some scoliotic spines, four plane regions may be detected. PMID:25031873

Interlimb reflex activity after spinal cord injury in man: strengthening response patterns are consistent with ongoing synaptic plasticity.

PubMed

Calancie, Blair; Alexeeva, Natalia; Broton, James G; Molano, Maria R

2005-01-01

Previous reports from our laboratory have described short-latency contractions in muscles of the distal upper limb following stimulation of lower limb nerves or skin in persons with injury to the cervical spinal cord. It takes 6 or more months for interlimb reflexes (ILR) to appear following acute spinal cord injury (SCI), suggesting they might be due to new synaptic interconnections between lower limb sensory afferents and motoneurons in the cervical enlargement. In this study, we asked if once formed, the strength of these synaptic connections increased over time, a finding that would be consistent with the above hypothesis. We studied persons with sub-acute and/or chronic cervical SCI. ILR were elicited by brief trains of electrical pulses applied to the skin overlying the tibial nerve at the back of the knee. Responses were quantified based on their presence or absence in different upper limb muscles. We also generated peri-stimulus time histograms for single motor unit response latency, probability, and peak duration. Comparisons of these parameters were made in subjects at sub-acute versus chronic stages post-injury. In persons with sub-acute SCI, the probability of seeing ILR in a given muscle of the forearm or hand was low at first, but increased substantially over the next 1-2 years. Motor unit responses at this sub-acute stage had a prolonged and variable latency, with a lower absolute response probability, compared to findings from subjects with chronic (i.e. stable) SCI. Our findings demonstrate that interlimb reflex activity, once established after SCI, shows signs of strengthening synaptic contacts between afferent and efferent components, consistent with ongoing synaptic plasticity. Neurons within the adult human spinal cord caudal to a lesion site are not static, but appear to be capable of developing novel-yet highly efficacious-synaptic contacts following trauma-induced partial denervation. In this case, such contacts between ascending afferents and cervical motoneurons do not appear to provide any functional benefit to the subject. In fact their presence may limit the regenerative effort of supraspinal pathways which originally innervated these motoneurons, should effort in animal models to promote regeneration across the lesion epicenter be successfully translated to humans with chronic SCI.

[Review of the regeneration mechanism of complete spinal cord injury].

PubMed

Li, Jiayin; Li, Xing; Xiao, Zhifeng; Dai, Jianwu

2018-06-01

Spinal cord injury (SCI), especially the complete SCI, usually results in complete paralysis below the level of the injury and seriously affects the patient's quality of life. SCI repair is still a worldwide medical problem. In the last twenty years, Professor DAI Jianwu and his team pioneered complete SCI model by removing spinal tissue with varied lengths in rodents, canine, and non-human primates to verify therapeutic effect of different repair strategies. Moreover, they also started the first clinical study of functional collagen scaffold on patients with acute complete SCI on January 16th, 2015. This review mainly focusses on the possible mechanisms responsible for complete SCI. In common, recovery of some sensory and motor functions post complete SCI include the following three contributing reasons. ① Regeneration of long ascending and descending axons throughout the lesion site to re-connect the original targets; ② New neural circuits formed in the lesion site by newly generated neurons post injury, which effectively re-connect the transected stumps; ③ The combined effect of ① and ②. The numerous studies have confirmed that neural circuits rebuilt across the injury site by newborn neurons might be the main mechanisms for functional recovery of animals from rodents to dogs. In many SCI model, especially the complete spinal cord transection model, many studies have convincingly demonstrated that the quantity and length of regenerated long descending axons, particularly like CST fibers, are too few to across the lesion site that is millimeters in length to realize motor functional recovery. Hence, it is more feasible in guiding neuronal relays formation by bio-scaffolds implantation than directing long motor axons regeneration in improving motor function of animals with complete spinal cord transection. However, some other issues such as promoting more neuronal relays formation, debugging wrong connections, and maintaining adequate neural circuits for functional recovery are urgent problems to be addressed.

Autonomic cardiovascular control and sports classification in Paralympic athletes with spinal cord injury.

PubMed

West, Christopher R; Krassioukov, Andrei V

2017-01-01

Purpose To investigate the relationship between the classification systems used in wheelchair sports and cardiovascular function in Paralympic athletes with spinal cord injury (SCI). Methods 26 wheelchair rugby (C3-C8) and 14 wheelchair basketball (T3-L1) were assessed for their International Wheelchair Rugby and Basketball Federation sports classification. Next, athletes were assessed for resting and reflex cardiovascular and autonomic function via the change (delta) in systolic blood pressure (SBP) and heart rate (HR) in response to sit-up, and sympathetic skin responses (SSRs), respectively. Results There were no differences in supine, seated, or delta SBP and HR between different sport classes in rugby or basketball (all p > 0.23). Athletes with autonomically complete injuries (SSR score 0-1) exhibited a lower supine SBP, seated SBP and delta SBP compared to those with autonomically incomplete injuries (SSR score >1; all p < 0.010), independent of sport played. There was no association between self-report OH and measured OH (χ 2  =   1.63, p = 0.20). Conclusion We provide definitive evidence that sports specific classification is not related to the degree of remaining autonomic cardiovascular control in Paralympic athletes with SCI. We suggest that testing for remaining autonomic function, which is closely related to the degree of cardiovascular control, should be incorporated into sporting classification. Implications for Rehabilitation Spinal cord injury is a debilitating condition that affects the function of almost every physiological system. It is becoming increasingly apparent that spinal cord injury induced changes in autonomic and cardiovascular function are important determinants of sports performance in athletes with spinal cord injury. This study shows that the current sports classification systems used in wheelchair rugby and basketball do not accurately reflect autonomic and cardiovascular function and thus are placing some athletes at a distinct disadvantage/advantage within their respective sport.

A dual physiological character for sexual function: libido and sexual pheromones.

PubMed

Motofei, Ion G

2009-12-01

Human sexual response is a complex function involving many cerebral, spinal and peripheral aspects; the last are relatively known and benefit from good pharmacological control, as in the case of erectile dysfunction. Spinal cord sexual reflexes also have a good theoretical and experimental description. There is minimal understanding of the cerebral sexual processes (libido, sexual arousal, orgasm). The initial perspective was that the cerebral areas implied in sexuality exert descending stimulatory and inhibitory influences on spinal cord sexual centres/reflexes. This was a wrong supposition, which inhibited progress in this subject, with a considerable impact on a subject's individual and social life. A new approach to sexual function arises from the idea that simple neurological structures can support only simple functions, while a more complex function requires correspondingly complex anatomical structures. For this reason the spinal cord would not be able to realise the integration of multiple (spinal and psychosensorial) stimuli into a unique and coherent ejaculation response. Consequently, all mechanisms implied in human sexuality would be cerebral processes, ejaculation reflexes ascending in evolution to the cerebral level. This new evolutionary concept was developed after 2001 in five distinct articles on the cerebral duality of sexual arousal, sexual hormones, ejaculation and serotonergic receptors. During this period other published results suggested a possible cerebral duality for sexual pheromones and libido in humans. All these dual physiological aspects are integrated in this review into one neurophysiological model, thus trying to further develop the new concepts of sexual function and perhaps relational behaviour. In conclusion, ejaculation is a dual cerebral process with arousal sensation (hormonally modulated) and libido perception (pheromonally modulated) as the afferent part. Two neurophysiological axes could exist in both men and women. In this assumption the mechanisms for libido and sexual arousal are not the only ones invoked, their correlations and implications are also suggested, perhaps critical aspects for further developments in the field.

New approach for graded compression spinal cord injuries in Rhesus macaque: method feasibility and preliminary observations.

PubMed

Guízar-Sahagún, Gabriel; Grijalva, Israel; Hernández-Godínez, Braulio; Franco-Bourland, Rebecca E; Cruz-Antonio, Leticia; Martínez-Cruz, Angelina; Ibáñez-Contreras, Alejandra; Madrazo, Ignacio

2011-12-01

Current models of spinal cord injury (SCI) have been ineffective for translational research. Primate blunt SCI, which more closely resembles human injury, could be a promising model to fill this gap. Graded compression SCI was produced by inflating at T9 an epidural balloon as a function of spinal canal dimensions in a non-uniform group of monkeys. Sham injury and cord compression by canal invasion of 50-75% produced minimal morpho-functional alterations, if at all. Canal invasion of 90-100% resulted in proportional functional deficits. Unexpectedly, these animals showed spontaneous gradual recovery over a 12-week period achieving quadruped walking, although with persistent absence of foot grasping reflex. Histopathology revealed predominance of central cord damage that correlated with functional status. Our preliminary results suggest that this model could potentially be a useful addition to translational work, but requires further validation by including animals with permanent injuries and expansion of replicates. © 2011 John Wiley & Sons A/S.

Effect of lycopene on the blood-spinal cord barrier after spinal cord injury in mice.

PubMed

Zhang, Qian; Wang, Jianbo; Gu, Zhengsong; Zhang, Qing; Zheng, Hong

2016-09-05

The current study aimed to investigate the effect of lycopene on the blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) in a mouse model. Lycopene inhibited lipid peroxidation and oxidative DNA damage as a highly efficient antioxidant and free radical scavenger. Lycopene (4 mg/kg/d) was administrated immediately following SCI. The permeability of the BSCB and water content in the spinal cord tissue were evaluated. Additionally, levels of expression of tight junction proteins and heme oxygenase-1 (HO-1) were determined with Western blotting. An enzyme-linked immunosorbent assay analysis of spinal cord tissue homogenates was performed 48 h after SCI to evaluate the expression of inflammation-related cytokines. In addition, recovery of motor function was assessed 1 d, 2 d, 5 d, 10 d, and 15 d after SCI using the Basso Mouse Scale to score locomotion. Compared to the group with an untreated SCI, mice with an SCI treated with lycopene had significantly reduced spinal cord tissue water content and BSCB permeability. Furthermore, motor function of mice with an SCI was also greatly improved by lycopene administration. The expression of the proinflammatory factors TNF-α and NF-kB increased markedly 48 h after SCI, and their upregulation was significantly attenuated by lycopene treatment. The expression of molecules that protect tight junctions, zonula occluden-1 and claudin-5, was upregulated by lycopene treatment after SCI. Taken together, these results clearly indicate that lycopene attenuated SCI by promoting repair of the damaged BSCB, so lycopene is a novel and promising treatment for SCI in humans.

Contributions of identifiable neurons and neuron classes to lamprey vertebrate neurobiology.

PubMed

Buchanan, J T

2001-03-01

Among the advantages offered by the lamprey brainstem and spinal cord for studies of the structure and function of the nervous system is the unique identifiability of several pairs of reticulospinal neurons in the brainstem. These neurons have been exploited in investigations of the patterns of sensory input to these cells and the patterns of their outputs to spinal neurons, but no doubt these cells could be used much more effectively in exploring their roles in descending control of the spinal cord. The variability of cell positions of neurons in the spinal cord has precluded the recognition of unique spinal neurons. However, classes of nerve cells can be readily defined and characterized within the lamprey spinal cord and this has led to progress in understanding the cellular and synaptic mechanisms of locomotor activity. In addition, both the identifiable reticulospinal cells and the various spinal nerve cell classes and their known synaptic interactions have been used to demonstrate the degree and specificity of regeneration within the lamprey nervous system. The lack of uniquely identifiable cells within the lamprey spinal cord has hampered progress in these areas, especially in gaining a full understanding of the locomotor network and how neuromodulation of the network is accomplished.

Spinal Disinhibition in Experimental and Clinical Painful Diabetic Neuropathy

PubMed Central

Marshall, Andrew G.; Lee-Kubli, Corinne; Azmi, Shazli; Zhang, Michael; Ferdousi, Maryam; Mixcoatl-Zecuatl, Teresa; Petropoulos, Ioannis N.; Ponirakis, Georgios; Fineman, Mark S.; Fadavi, Hassan; Frizzi, Katie; Tavakoli, Mitra; Jolivalt, Corinne G.; Boulton, Andrew J.M.; Efron, Nathan; Calcutt, Nigel A.

2017-01-01

Impaired rate-dependent depression (RDD) of the Hoffman reflex is associated with reduced dorsal spinal cord potassium chloride cotransporter expression and impaired spinal γ-aminobutyric acid type A receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia. Impaired RDD in diabetic rats was rapidly normalized by spinal delivery of duloxetine acting via 5-hydroxytryptamine type 2A receptors and temporally coincident with the alleviation of allodynia. Deficits in RDD and corneal nerve density were demonstrated in patients with painful diabetic neuropathy compared with healthy control subjects and patients with painless diabetic neuropathy. Spinal inhibitory dysfunction and peripheral small fiber pathology may contribute to the clinical phenotype in painful diabetic neuropathy. Deficits in RDD may help identify patients with spinally mediated painful diabetic neuropathy who may respond optimally to therapies such as duloxetine. PMID:28202580

Effect of low-energy extracorporeal shock wave on vascular regeneration after spinal cord injury and the recovery of motor function.

PubMed

Wang, Lei; Jiang, Yuquan; Jiang, Zheng; Han, Lizhang

2016-01-01

Latest studies show that low-energy extracorporeal shock wave therapy (ESWT) can upregulate levels of vascular endothelial growth factor (VEGF). VEGF can ease nervous tissue harm after spinal cord injury (SCI). This study aims to explore whether low-energy ESWT can promote expression of VEGF, protect nervous tissue after SCI, and improve motor function. Ninety adult female rats were divided into the following groups: Group A (simple laminectomy), Group B (laminectomy and low-energy ESWT), Group C (spinal cord injury), and Group D (spinal cord injury and low-energy ESWT). Impinger was used to cause thoracic spinal cord injury. Low-energy ESWT was applied as treatment after injury three times a week, for 3 weeks. After SCI, the Basso, Beattie, and Bresnahan (BBB) scale was used to evaluate motor function over a period of 42 days at different time points. Hematoxylin and eosin (HE) staining was used to evaluate nerve tissue injury. Neuronal nuclear antigen (NeuN) staining was also used to evaluate loss of neurons. Polymerase chain reaction was used to detect messenger RNA (mRNA) expression of VEGF and its receptor fms-like tyrosine kinase 1 (Flt-1). Immunostaining was used to evaluate VEGF protein expression level in myeloid tissue. BBB scores of Groups A and B showed no significant result related to dyskinesia. HE and NeuN staining indicated that only using low-energy ESWT could not cause damage of nervous tissue in Group B. Recovery of motor function at 7, 35, and 42 days after SCI in Group D was better than that in Group C (P<0.05). Compared with Group C, number of NeuN-positive cells at 42 days after SCI increased significantly (P<0.05). The mRNA levels of VEGF and Flt-1 and VEGF expression at 7 days after SCI in Group D were significantly higher than those in Group C (P<0.05). Low-energy ESWT promotes expression of VEGF, decreases secondary damage of nerve tissue, and improves recovery of motor function. It can be regarded as one mode of clinical routine adjunctive therapy for spinal injury.

Movement rehabilitation after spinal cord injuries: emerging concepts and future directions.

PubMed

Marsh, Barnaby C; Astill, Sarah L; Utley, Andrea; Ichiyama, Ronaldo M

2011-03-10

Considerable inroads are being made into developing new treatments for spinal cord injury (SCI) which aim to facilitate functional recovery, including locomotion. Research on rehabilitative strategies following SCI using animal models has demonstrated that regaining and maintaining motor function, such as standing or stepping, is governed by principles of skill acquisition. Mechanisms key to learning motor tasks, including retention and transfer of skill, feedback and conditions of practice, all have examples in the SCI animal literature, although the importance of many concepts may often be overlooked. Combinatorial strategies which include physical rehabilitation are beginning to yield promising results. However, the effects of molecular-cellular interventions including chondroitinaseABC, anti-NogoA, foetal stem cell transplantation, etc., are still poorly understood with reference to the changes made to spinal plasticity by training and exercise. Studies that investigate the interplay between rehabilitation and other treatments have had mixed results; it appears likely that precise timings of different interventions will help to maximize recovery of function. Understanding how the time-course of injury and different rehabilitative and treatment modalities might factor into spinal plasticity will be critical in future therapeutic interventions. Copyright © 2010 Elsevier Inc. All rights reserved.

Assessing denoising strategies to increase signal to noise ratio in spinal cord and in brain cortical and subcortical regions

NASA Astrophysics Data System (ADS)

Maugeri, L.; Moraschi, M.; Summers, P.; Favilla, S.; Mascali, D.; Cedola, A.; Porro, C. A.; Giove, F.; Fratini, M.

2018-02-01

Functional Magnetic Resonance Imaging (fMRI) based on Blood Oxygenation Level Dependent (BOLD) contrast has become one of the most powerful tools in neuroscience research. On the other hand, fMRI approaches have seen limited use in the study of spinal cord and subcortical brain regions (such as the brainstem and portions of the diencephalon). Indeed obtaining good BOLD signal in these areas still represents a technical and scientific challenge, due to poor control of physiological noise and to a limited overall quality of the functional series. A solution can be found in the combination of optimized experimental procedures at acquisition stage, and well-adapted artifact mitigation procedures in the data processing. In this framework, we studied two different data processing strategies to reduce physiological noise in cortical and subcortical brain regions and in the spinal cord, based on the aCompCor and RETROICOR denoising tools respectively. The study, performed in healthy subjects, was carried out using an ad hoc isometric motor task. We observed an increased signal to noise ratio in the denoised functional time series in the spinal cord and in the subcortical brain region.

A comparison of Espocan and Tuohy needles for the combined spinal-epidural technique for labor analgesia.

PubMed

Browne, Ingrid M; Birnbach, David J; Stein, Deborah J; O'Gorman, David A; Kuroda, Maxine

2005-08-01

When using the needle-through-needle combined spinal-epidural (CSE) technique for labor analgesia, failure to obtain cerebrospinal fluid (CSF), paresthesias, and intrathecal or intravascular migration of the catheter are of concern. Epidural needles with spinal needle apertures, such as the back-hole Espocan (ES) needles, are available and may reduce these risks. We describe the efficacy and adverse events associated with a modified epidural needle (ES) versus a conventional Tuohy needle for CSE. One-hundred parturients requesting labor analgesia (CSE) were randomized into 2 groups: 50-ES 18-gauge modified epidural needle with 27-gauge Pencan atraumatic spinal needle, 50-conventional 18-gauge Tuohy needle with 27-gauge Gertie Marx atraumatic spinal needle. Information on intrathecal or intravascular catheter placement, paresthesia on introduction of spinal needle, failure to obtain CSF through the spinal needle after placement of epidural needle, unintentional dural puncture, and epidural catheter function was obtained. No intrathecal catheter placement occurred in either group. Rates of intravascular catheter placement and unintentional dural puncture were similar between the groups. Significant differences were noted regarding spinal needle-induced paresthesia (14% ES versus 42% Tuohy needles, P = 0.009) and failure to obtain CSF on first attempt (8% ES versus 28% Tuohy needles, P < 0.02). Use of ES needles for CSE significantly reduces paresthesia associated with the insertion of the spinal needle and is associated with more frequent successful spinal needle placement on the first attempt. The use of modified epidural needles with a back hole for combined spinal-epidural technique significantly reduces paresthesia associated with the insertion of the spinal needle and is associated with more frequent successful spinal needle placement on the first attempt.

Sensorimotor Integration by Corticospinal System

PubMed Central

Moreno-López, Yunuen; Olivares-Moreno, Rafael; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

2016-01-01

The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, the CS descending projection plays a major role in motor command, which results from direct and indirect control of spinal cord pre-motor interneurons as well as motoneurons. But in addition, this system is also involved in a selective and complex modulation of sensory feedback. Despite recent evidence confirms that CS projections drive distinct segmental neural circuits that are part of the sensory and pre-motor pathways, little is known about the spinal networks engaged by the corticospinal tract (CST), the organization of CS projections, the intracortical microcircuitry, and the synaptic interactions in the sensorimotor cortex (SMC) that may encode different cortical outputs to the spinal cord. Here is stressed the importance of integrated approaches for the study of sensorimotor function of CS system, in order to understand the functional compartmentalization and hierarchical organization of layer 5 output neurons, who are key elements for motor control and hence, of behavior. PMID:27013985

Sensorimotor Integration by Corticospinal System.

PubMed

Moreno-López, Yunuen; Olivares-Moreno, Rafael; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

2016-01-01

The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, the CS descending projection plays a major role in motor command, which results from direct and indirect control of spinal cord pre-motor interneurons as well as motoneurons. But in addition, this system is also involved in a selective and complex modulation of sensory feedback. Despite recent evidence confirms that CS projections drive distinct segmental neural circuits that are part of the sensory and pre-motor pathways, little is known about the spinal networks engaged by the corticospinal tract (CST), the organization of CS projections, the intracortical microcircuitry, and the synaptic interactions in the sensorimotor cortex (SMC) that may encode different cortical outputs to the spinal cord. Here is stressed the importance of integrated approaches for the study of sensorimotor function of CS system, in order to understand the functional compartmentalization and hierarchical organization of layer 5 output neurons, who are key elements for motor control and hence, of behavior.

Generation of Spinal Motor Neurons from Human Pluripotent Stem Cells.

PubMed

Santos, David P; Kiskinis, Evangelos

2017-01-01

Human embryonic stem cells (ESCs) are characterized by their unique ability to self-renew indefinitely, as well as to differentiate into any cell type of the human body. Induced pluripotent stem cells (iPSCs) share these salient characteristics with ESCs and can easily be generated from any given individual by reprogramming somatic cell types such as fibroblasts or blood cells. The spinal motor neuron (MN) is a specialized neuronal subtype that synapses with muscle to control movement. Here, we present a method to generate functional, postmitotic, spinal motor neurons through the directed differentiation of ESCs and iPSCs by the use of small molecules. These cells can be utilized to study the development and function of human motor neurons in healthy and disease states.

Agmatine improves locomotor function and reduces tissue damage following spinal cord injury.

PubMed

Yu, C G; Marcillo, A E; Fairbanks, C A; Wilcox, G L; Yezierski, R P

2000-09-28

Clinically effective drug treatments for spinal cord injury (SCI) remain unavailable. Agmatine, an NMDA receptor antagonist and inhibitor of nitric oxide synthase (NOS), is an endogenous neuromodulator found in the brain and spinal cord. Evidence is presented that agmatine significantly improves locomotor function and reduces tissue damage following traumatic SCI in rats. The results suggest the importance of future therapeutic strategies encompassing the use of single drugs with multiple targets for the treatment of acute SCI. The therapeutic targets of agmatine (NMDA receptor and NOS) have been shown to be critically linked to the pathophysiological sequelae of CNS injury and this, combined with the non-toxic profile, lends support to agmatine being considered as a potential candidate for future clinical applications.

Administration of low dose estrogen attenuates persistent inflammation, promotes angiogenesis, and improves locomotor function following chronic spinal cord injury in rats.

PubMed

Samantaray, Supriti; Das, Arabinda; Matzelle, Denise C; Yu, Shan P; Wei, Ling; Varma, Abhay; Ray, Swapan K; Banik, Naren L

2016-05-01

Spinal cord injury (SCI) causes loss of neurological function and, depending upon the severity of injury, may lead to paralysis. Currently, no FDA-approved pharmacotherapy is available for SCI. High-dose methylprednisolone is widely used, but this treatment is controversial. We have previously shown that low doses of estrogen reduces inflammation, attenuates cell death, and protects axon and myelin in SCI rats, but its effectiveness in recovery of function is not known. Therefore, the goal of this study was to investigate whether low doses of estrogen in post-SCI would reduce inflammation, protect cells and axons, and improve locomotor function during the chronic phase of injury. Injury (40 g.cm force) was induced at thoracic 10 in young adult male rats. Rats were treated with 10 or 100 μg 17β-estradiol (estrogen) for 7 days following SCI and compared with vehicle-treated injury and laminectomy (sham) controls. Histology (H&E staining), immunohistofluorescence, Doppler laser technique, and Western blotting were used to monitor tissue integrity, gliosis, blood flow, angiogenesis, the expression of angiogenic factors, axonal degeneration, and locomotor function (Basso, Beattie, and Bresnahan rating) following injury. To assess the progression of recovery, rats were sacrificed at 7, 14, or 42 days post injury. A reduction in glial reactivity, attenuation of axonal and myelin damage, protection of cells, increased expression of angiogenic factors and microvessel growth, and improved locomotor function were found following estrogen treatment compared with vehicle-treated SCI rats. These results suggest that treatment with a very low dose of estrogen has significant therapeutic implications for the improvement of locomotor function in chronic SCI. Experimental studies with low dose estrogen therapy in chronic spinal cord injury (SCI) demonstrated the potential for multi-active beneficial outcomes that could ameliorate the degenerative pathways in chronic SCI as shown in (a). Furthermore, the alterations in local spinal blood flow could be significantly alleviated with low dose estrogen therapy. This therapy led to the preservation of the structural integrity of the spinal cord (b), which in turn led to the improved functional recovery as shown (c). © 2016 International Society for Neurochemistry.

Cellular Scaling Rules for Primate Spinal Cords

PubMed Central

Burish, Mark J.; Peebles, J. Klint; Baldwin, Mary K.; Tavares, Luciano; Kaas, Jon H.; Herculano-Houzel, Suzana

2010-01-01

The spinal cord can be considered a major sensorimotor interface between the body and the brain. How does the spinal cord scale with body and brain mass, and how are its numbers of neurons related to the number of neurons in the brain across species of different body and brain sizes? Here we determine the cellular composition of the spinal cord in eight primate species and find that its number of neurons varies as a linear function of cord length, and accompanies body mass raised to an exponent close to 1/3. This relationship suggests that the extension, mass and number of neurons that compose the spinal cord are related to body length, rather than to body mass or surface. Moreover, we show that although brain mass increases linearly with cord mass, the number of neurons in the brain increases with the number of neurons in the spinal cord raised to the power of 1.7. This faster addition of neurons to the brain than to the spinal cord is consistent with current views on how larger brains add complexity to the processing of environmental and somatic information. PMID:20926855

Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia

NASA Technical Reports Server (NTRS)

Zeitzer, J. M.; Ayas, N. T.; Shea, S. A.; Brown, R.; Czeisler, C. A.

2000-01-01

The human circadian timing system regulates the temporal organization of several endocrine functions, including the production of melatonin (via a neural pathway that includes the spinal cord), TSH, and cortisol. In traumatic spinal cord injury, afferent and efferent circuits that influence the basal production of these hormones may be disrupted. We studied five subjects with chronic spinal cord injury (three tetraplegic and two paraplegic, all neurologically complete injuries) under stringent conditions in which the underlying circadian rhythmicity of these hormones could be examined. Melatonin production was absent in the three tetraplegic subjects with injury to their lower cervical spinal cord and was of normal amplitude and timing in the two paraplegic subjects with injury to their upper thoracic spinal cord. The amplitude and the timing of TSH and cortisol rhythms were robust in the paraplegics and in the tetraplegics. Our results indicate that neurologically complete cervical spinal injury results in the complete loss of pineal melatonin production and that neither the loss of melatonin nor the loss of spinal afferent information disrupts the rhythmicity of cortisol or TSH secretion.

Effects of aquatic exercise on physical function and fitness among people with spinal cord injury: A systematic review.

PubMed

Li, Chunxiao; Khoo, Selina; Adnan, Athirah

2017-03-01

The aim of this review is to synthesize the evidence on the effects of aquatic exercise interventions on physical function and fitness among people with spinal cord injury. Six major databases were searched from inception till June 2015: MEDLINE, CINAHL, EMBASE, PsychInfo, SPORTDiscus, and Cochrane Center Register of Controlled Trials. Two reviewers independently rated methodological quality using the modified Downs and Black Scale and extracted and synthesized key findings (i.e., participant characteristics, study design, physical function and fitness outcomes, and adverse events). Eight of 276 studies met the inclusion criteria, of which none showed high research quality. Four studies assessed physical function outcomes and 4 studies evaluated aerobic fitness as outcome measures. Significant improvements on these 2 outcomes were generally found. Other physical or fitness outcomes including body composition, muscular strength, and balance were rarely reported. There is weak evidence supporting aquatic exercise training to improve physical function and aerobic fitness among adults with spinal cord injury. Suggestions for future research include reporting details of exercise interventions, evaluating other physical or fitness outcomes, and improving methodological quality.

Optimization of Spinal Muscular Atrophy subject's muscle activity during gait

NASA Astrophysics Data System (ADS)

Umat, Gazlia; Rambely, Azmin Sham

2014-06-01

Spinal Muscular Atrophy (SMA) is a hereditary disease related muscle nerve disorder caused by degeneration of the anterior cells of the spinal cord. SMA is divided into four types according to the degree of seriousness. SMA patients show different gait with normal people. Therefore, this study focused on the effects of SMA patient muscle actions and the difference that exists between SMA subjects and normal subjects. Therefore, the electromyography (EMG) test will be used to track the behavior of muscle during walking and optimization methods are used to get the muscle stress that is capable of doing the work while walking. Involved objective function is non-linear function of the quadratic and cubic functions. The study concludes with a comparison of the objective function using the force that sought to use the moment of previous studies and the objective function using the data obtained from EMG. The results shows that the same muscles, peroneus longus and bisepsfemoris, were used during walking activity by SMA subjects and control subjects. Muscle stress force best solution achieved from part D in simulation carried out.

Combined polymer-curcumin conjugate and ependymal progenitor/stem cell treatment enhances spinal cord injury functional recovery.

PubMed

Requejo-Aguilar, Raquel; Alastrue-Agudo, Ana; Cases-Villar, Marta; Lopez-Mocholi, Eric; England, Richard; Vicent, María J; Moreno-Manzano, Victoria

2017-01-01

Spinal cord injury (SCI) suffers from a lack of effective therapeutic strategies. Animal models of acute SCI have provided evidence that transplantation of ependymal stem/progenitor cells of the spinal cord (epSPCs) induces functional recovery, while systemic administration of the anti-inflammatory curcumin provides neuroprotection. However, functional recovery from chronic stage SCI requires additional enhancements in available therapeutic strategies. Herein, we report on a combination treatment for SCI using epSPCs and a pH-responsive polymer-curcumin conjugate. The incorporation of curcumin in a pH-responsive polymeric carrier mainchain, a polyacetal (PA), enhances blood bioavailability, stability, and provides a means for highly localized delivery. We find that PA-curcumin enhances neuroprotection, increases axonal growth, and can improve functional recovery in acute SCI. However, when combined with epSPCs, PA-curcumin also enhances functional recovery in a rodent model of chronic SCI. This suggests that combination therapy may be an exciting new therapeutic option for the treatment of chronic SCI in humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

Increasing Rates of Surgical Management of Multilevel Spinal Curvature in Elderly Patients.

PubMed

Sing, David C; Khanna, Ryan; Shaw, Jeremy D; Metz, Lionel N; Burch, Shane; Berven, Sigurd H

2016-09-01

Retrospective analysis of Nationwide Inpatient Sample (NIS) database. To analyze trends in utilization and hospital charges for multilevel spinal curvature surgery in patients over 60 from 2004 to 2011. Multilevel spinal curvature has been increasingly recognized as a major source of morbidity in patients over sixty years of age. The economic burden of non-operative management for spinal curvature is elusive and likely underestimated. Though patient reported outcomes suggest that surgical treatment of spinal curvature may be superior to non-operative treatment in selected patients, surgical utilization trends remain unclear. Data were obtained from the NIS between 2004 and 2011. The NIS is the largest all-payer inpatient care database with approximately eight million annual patient discharges throughout the United States. Analysis included patients over age 60 with a spinal curvature diagnosis treated with a multi-level spinal fusion (≥3 levels fused) determined by ICD-9-CM diagnosis and procedure codes. Population-based utilization rates were calculated from US census data. A total of 84,302 adult patients underwent multilevel spinal curvature surgery from 2004 to 2011. The annual number of ≥3 level spinal curvature fusions in patients over age 60 increased from 6,571 to 16,526, representing a 107.8% increase from 13.4 cases per 100,000 people in 2004 to 27.9 in 2011 (p < .001). Utilization rates in patients 65-69 years old experienced the greatest growth, increasing by 122% from 15.8 cases per 100,000 people to 35.1. Average hospital charges increased 108% from $90,557 in 2007 to $188,727 in 2011 (p < .001). Rates of surgical management of multilevel spinal curvature increased from 2004 to 2011, exceeding growth of the 60+ age demographic during the same period. Growth was observed in all age demographics, and hospital charges consistently increased from 2004 to 2011 reflecting a per-user increase in expenditure. III. Copyright © 2016 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

Pathological lesions in the central nervous system and peripheral tissues of ddY mice with street rabies virus (1088 strain).

PubMed

Kimitsuki, Kazunori; Yamada, Kentaro; Shiwa, Nozomi; Inoue, Satoshi; Nishizono, Akira; Park, Chun-Ho

2017-06-10

Most studies on rabies virus pathogenesis in animal models have employed fixed rabies viruses, and the results of those employing street rabies viruses have been inconsistent. Therefore, to clarify the pathogenesis of street rabies virus (1088 strain) in mice, 10 6 focus forming units were inoculated into the right hindlimb of ddY mice (6 weeks, female). At 3 days postinoculation (DPI), mild inflammation was observed in the hindlimb muscle. At 5 DPI, ganglion cells in the right lumbosacral spinal dorsal root ganglia showed chromatolysis. Axonal degeneration and inflammatory cells increased with infection progress in the spinal dorsal horn and dorsal root ganglia. Right hindlimb paralysis was observed from 7 DPI, which progressed to quadriparalysis. However, no pathological changes were observed in the ventral horn and root fibers of the spinal cord. Viral antigen was first detected in the right hindlimb muscle at 3 DPI, followed by the right lumbosacral dorsal root ganglia, dorsal horn of spinal cord, left red nuclei, medulla oblongata and cerebral cortex (M1 area) at 5 DPI. These results suggested that the 1088 virus ascended the lumbosacral spinal cord via mainly afferent fibers at early stage of infection and moved to cerebral cortex (M1 area) using descending spinal tract. Additionally, we concluded that significant pathological changes in mice infected with 1088 strain occur in the sensory tract of the spinal cord; this selective susceptibility results in clinical features of the disease.

[Patient management in polytrauma with injuries of the cervical spine].

PubMed

Kohler, A; Friedl, H P; Käch, K; Stocker, R; Trentz, O

1994-04-01

Complex unstable cervical spine injuries in polytraumatized patients are stabilized ventro-dorsally in a two-stage procedure. The ventral stabilization is a day-one surgery with the goal to get primary stability for intensive care, early spinal decompression and protection against secondary damage of the spinal cord. The additional dorsal stabilization allows early functional treatment or in case of spinal cord lesions early neurorehabilitation. The combination of severe brain injury and unstable cervical spine injury is especially demanding concerning diagnostic and therapeutic procedures.

Acute intraparenchymal spinal cord injury in a cat due to high-rise syndrome.

PubMed

Cruz-Arámbulo, Robert; Nykamp, Stephanie

2012-03-01

A 9-year-old spayed female Bengal Red cat was evaluated for high-rise syndrome. The cat had paraplegia of the hind limbs, intact reflexes and pain perception, and hyperesthesia in the caudal thoracic area. Mentation, cranial nerve function, forelimb proprioceptive responses, and spinal reflexes were normal. There were no abnormalities on radiographs or computed tomography scan, but magnetic resonance imaging revealed a hyperintense intraparenchymal spinal cord lesion on T2-weighted and T2 fat saturation images.

Karolinska institutet 200-year anniversary. Symposium on traumatic injuries in the nervous system: injuries to the spinal cord and peripheral nervous system - injuries and repair, pain problems, lesions to brachial plexus.

PubMed

Sköld, Mattias K; Svensson, Mikael; Tsao, Jack; Hultgren, Thomas; Landegren, Thomas; Carlstedt, Thomas; Cullheim, Staffan

2011-01-01

The Karolinska Institutet 200-year anniversary symposium on injuries to the spinal cord and peripheral nervous system gathered expertise in the spinal cord, spinal nerve, and peripheral nerve injury field spanning from molecular prerequisites for nerve regeneration to clinical methods in nerve repair and rehabilitation. The topics presented at the meeting covered findings on adult neural stem cells that when transplanted to the hypoglossal nucleus in the rat could integrate with its host and promote neuron survival. Studies on vascularization after intraspinal replantation of ventral nerve roots and microarray studies in ventral root replantation as a tool for mapping of biological patterns typical for neuronal regeneration were discussed. Different immune molecules in neurons and glia and their very specific roles in synapse plasticity after injury were presented. Novel strategies in repair of injured peripheral nerves with ethyl-cyanoacrylate adhesive showed functional recovery comparable to that of conventional epineural sutures. Various aspects on surgical techniques which are available to improve function of the limb, once the nerve regeneration after brachial plexus lesions and repair has reached its limit were presented. Moreover, neurogenic pain after amputation and its treatment with mirror therapy were shown to be followed by dramatic decrease in phantom limb pain. Finally clinical experiences on surgical techniques to repair avulsed spinal nerve root and the motoric as well as sensoric regain of function were presented.

Karolinska Institutet 200-Year Anniversary. Symposium on Traumatic Injuries in the Nervous System: Injuries to the Spinal Cord and Peripheral Nervous System – Injuries and Repair, Pain Problems, Lesions to Brachial Plexus

PubMed Central

Sköld, Mattias K.; Svensson, Mikael; Tsao, Jack; Hultgren, Thomas; Landegren, Thomas; Carlstedt, Thomas; Cullheim, Staffan

2011-01-01

The Karolinska Institutet 200-year anniversary symposium on injuries to the spinal cord and peripheral nervous system gathered expertise in the spinal cord, spinal nerve, and peripheral nerve injury field spanning from molecular prerequisites for nerve regeneration to clinical methods in nerve repair and rehabilitation. The topics presented at the meeting covered findings on adult neural stem cells that when transplanted to the hypoglossal nucleus in the rat could integrate with its host and promote neuron survival. Studies on vascularization after intraspinal replantation of ventral nerve roots and microarray studies in ventral root replantation as a tool for mapping of biological patterns typical for neuronal regeneration were discussed. Different immune molecules in neurons and glia and their very specific roles in synapse plasticity after injury were presented. Novel strategies in repair of injured peripheral nerves with ethyl-cyanoacrylate adhesive showed functional recovery comparable to that of conventional epineural sutures. Various aspects on surgical techniques which are available to improve function of the limb, once the nerve regeneration after brachial plexus lesions and repair has reached its limit were presented. Moreover, neurogenic pain after amputation and its treatment with mirror therapy were shown to be followed by dramatic decrease in phantom limb pain. Finally clinical experiences on surgical techniques to repair avulsed spinal nerve root and the motoric as well as sensoric regain of function were presented. PMID:21629875

Technical Rebuilding of Movement Function Using Functional Electrical Stimulation

NASA Astrophysics Data System (ADS)

Gföhler, Margit

To rebuild lost movement functions, neuroprostheses based on functional electrical stimulation (FES) artificially activate skeletal muscles in corresponding sequences, using both residual body functions and artificial signals for control. Besides the functional gain, FES training also brings physiological and psychological benefits for spinal cord-injured subjects. In this chapter, current stimulation technology and the main components of FES-based neuroprostheses including enhanced control systems are presented. Technology and application of FES cycling and rowing, both approaches that enable spinal cord-injured subjects to participate in mainstream activities and improve their health and fitness by exercising like able-bodied subjects, are discussed in detail, and an overview of neuroprostheses that aim at restoring movement functions for daily life as walking or grasping is given.

Longitudinal Recovery and Reduced Costs After 120 Sessions of Locomotor Training for Motor Incomplete Spinal Cord Injury.

PubMed

Morrison, Sarah A; Lorenz, Douglas; Eskay, Carol P; Forrest, Gail F; Basso, D Michele

2018-03-01

To determine the impact of long-term, body weight-supported locomotor training after chronic, incomplete spinal cord injury (SCI), and to estimate the health care costs related to lost recovery potential and preventable secondary complications that may have occurred because of visit limits imposed by insurers. Prospective observational cohort with longitudinal follow-up. Eight outpatient rehabilitation centers that participate in the Christopher & Dana Reeve Foundation NeuroRecovery Network (NRN). Individuals with motor incomplete chronic SCI (American Spinal Injury Association Impairment Scale C or D; N=69; 0.1-45y after SCI) who completed at least 120 NRN physical therapy sessions. Manually assisted locomotor training (LT) in a body weight-supported treadmill environment, overground standing and stepping activities, and community integration tasks. International Standards for Neurological Classification of Spinal Cord Injury motor and sensory scores, orthostatic hypotension, bowel/bladder/sexual function, Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI), Berg Balance Scale, Modified Functional Reach, 10-m walk test, and 6-minute walk test. Longitudinal outcome measure collection occurred every 20 treatments and at 6- to 12-month follow-up after discharge from therapy. Significant improvement occurred for upper and lower motor strength, functional activities, psychological arousal, sensation of bowel movement, and SCI-FAI community ambulation. Extended training enabled minimal detectable changes at 60, 80, 100, and 120 sessions. After detectable change occurred, it was sustained through 120 sessions and continued 6 to 12 months after treatment. Delivering at least 120 sessions of LT improves recovery from incomplete chronic SCI. Because walking reduces rehospitalization, LT delivered beyond the average 20-session insurance limit can reduce rehospitalizations and long-term health costs. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord

PubMed Central

Gozal, Elizabeth A.; O'Neill, Brannan E.; Sawchuk, Michael A.; Zhu, Hong; Halder, Mallika; Chou, Ching-Chieh; Hochman, Shawn

2014-01-01

The trace amines (TAs), tryptamine, tyramine, and β-phenylethylamine, are synthesized from precursor amino acids via aromatic-L-amino acid decarboxylase (AADC). We explored their role in the neuromodulation of neonatal rat spinal cord motor circuits. We first showed that the spinal cord contains the substrates for TA biosynthesis (AADC) and for receptor-mediated actions via trace amine-associated receptors (TAARs) 1 and 4. We next examined the actions of the TAs on motor activity using the in vitro isolated neonatal rat spinal cord. Tyramine and tryptamine most consistently increased motor activity with prominent direct actions on motoneurons. In the presence of N-methyl-D-aspartate, all applied TAs supported expression of a locomotor-like activity (LLA) that was indistinguishable from that ordinarily observed with serotonin, suggesting that the TAs act on common central pattern generating neurons. The TAs also generated distinctive complex rhythms characterized by episodic bouts of LLA. TA actions on locomotor circuits did not require interaction with descending monoaminergic projections since evoked LLA was maintained following block of all Na+-dependent monoamine transporters or the vesicular monoamine transporter. Instead, TA (tryptamine and tyramine) actions depended on intracellular uptake via pentamidine-sensitive Na+-independent membrane transporters. Requirement for intracellular transport is consistent with the TAs having much slower LLA onset than serotonin and for activation of intracellular TAARs. To test for endogenous actions following biosynthesis, we increased intracellular amino acid levels with cycloheximide. LLA emerged and included distinctive TA-like episodic bouts. In summary, we provided anatomical and functional evidence of the TAs as an intrinsic spinal monoaminergic modulatory system capable of promoting recruitment of locomotor circuits independent of the descending monoamines. These actions support their known sympathomimetic function. PMID:25426030

Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord.

PubMed

Gozal, Elizabeth A; O'Neill, Brannan E; Sawchuk, Michael A; Zhu, Hong; Halder, Mallika; Chou, Ching-Chieh; Hochman, Shawn

2014-01-01

The trace amines (TAs), tryptamine, tyramine, and β-phenylethylamine, are synthesized from precursor amino acids via aromatic-L-amino acid decarboxylase (AADC). We explored their role in the neuromodulation of neonatal rat spinal cord motor circuits. We first showed that the spinal cord contains the substrates for TA biosynthesis (AADC) and for receptor-mediated actions via trace amine-associated receptors (TAARs) 1 and 4. We next examined the actions of the TAs on motor activity using the in vitro isolated neonatal rat spinal cord. Tyramine and tryptamine most consistently increased motor activity with prominent direct actions on motoneurons. In the presence of N-methyl-D-aspartate, all applied TAs supported expression of a locomotor-like activity (LLA) that was indistinguishable from that ordinarily observed with serotonin, suggesting that the TAs act on common central pattern generating neurons. The TAs also generated distinctive complex rhythms characterized by episodic bouts of LLA. TA actions on locomotor circuits did not require interaction with descending monoaminergic projections since evoked LLA was maintained following block of all Na(+)-dependent monoamine transporters or the vesicular monoamine transporter. Instead, TA (tryptamine and tyramine) actions depended on intracellular uptake via pentamidine-sensitive Na(+)-independent membrane transporters. Requirement for intracellular transport is consistent with the TAs having much slower LLA onset than serotonin and for activation of intracellular TAARs. To test for endogenous actions following biosynthesis, we increased intracellular amino acid levels with cycloheximide. LLA emerged and included distinctive TA-like episodic bouts. In summary, we provided anatomical and functional evidence of the TAs as an intrinsic spinal monoaminergic modulatory system capable of promoting recruitment of locomotor circuits independent of the descending monoamines. These actions support their known sympathomimetic function.

A multi-train electrical stimulation protocol facilitates transcranial electrical motor evoked potentials and increases induction rate and reproducibility even in patients with preoperative neurological deficits.

PubMed

Ushio, Shuta; Kawabata, Shigenori; Sumiya, Satoshi; Kato, Tsuyoshi; Yoshii, Toshitaka; Yamada, Tsuyoshi; Enomoto, Mitsuhiro; Okawa, Atsushi

2018-06-01

This study sought to evaluate the facilitation effect of repetitive multi-train transcranial electrical stimulation (mt-TES) at 2 repetition rates on transcranial electrical motor evoked potential (Tc-MEP) monitoring during spinal surgery, and to assess the induction rate in patients with impaired motor function from a compromised spinal cord or spinal nerve. We studied 32 consecutive patients with impaired motor function undergoing cervical or thoracic spinal surgery (470 muscles). A series of 10 TESs with 5 pulse trains were preoperatively delivered at 2 repetition rates (1 and 5 Hz). All peak-topeak amplitudes of the MEPs of the upper and lower extremity muscles elicited by the 10 TESs were measured. The induction rates of the lower extremity muscles were also assessed with muscle and preoperative lower extremity motor function scores. In each of the muscles, MEP amplitudes were augmented by about 2-3 times at 1 Hz and 5-6 times at 5 Hz. Under the 5-Hz condition, all limb muscles showed significant amplification. Also, in all preoperative motor function score groups, the amplitudes and induction rates of the lower extremity muscles were significantly increased. Moreover, the facilitation effects tended to peak in the last half of the series of 10 TESs. In all score groups of patients with preoperative neurological deficits, repetitive mt-TES delivered at a frequency of 5 Hz markedly facilitated the MEPs of all limb muscles and increased the induction rate. We recommend this method to improve the reliability of intraoperative monitoring during spinal surgery.

Sexual Functioning in Men Living with a Spinal Cord Injury–A Narrative Literature Review

PubMed Central

Sunilkumar, MM; Boston, Patricia; Rajagopal, MR

2015-01-01

Background: Sexual dysfunction is a major concern for Indian men living with a spinal cord injury Objectives: To examine the literature related to sexuality traumatic cord injury and its impact on sexual functioning. Materials and Methods: Databases using Cumulative Index to Nursing and Allied Health Literature (CINAHL) 2000–2012, Medline 1989–2012, Applied Social Sciences Index and Abstracts (ASSIA) 1989–2012 and Google Scholar were the search engines used used for literature review. Results: The search yielded a total of 457 articles and only 75 of them were found relevant. The minimum number of articles required to meet the inclusion criteria for this review was 25–30 articles. Out of the 75 articles, 33 were considered relevant or related to the topic of sexual functioning, spinal cord injury, and paraplegia. Six areas were identified: Sexual stigmatization, physiological barriers to sexual satisfaction, clinical aspects of sexual functioning, biomedical approaches to sexual dysfunction, partner satisfaction, and lack of accessibility to sexual education. Conclusion: Spinal cord injury and sexual functioning affects a large segment of the male Indian population, yet most current research focuses on quantitative measurement with the emphasis on ejaculatory dysfunction, orgasm impairment, incontinence, and other physiological dysfunction. Further research is needed to address the subjective accounts of patients themselves with respect to the emotional and social impact of sexual disability. This would help to identify the best possible outcomes for both treatment and rehabilitation. PMID:26600694

Supraspinal Control Predicts Locomotor Function and Forecasts Responsiveness to Training after Spinal Cord Injury

PubMed Central

Field-Fote, Edelle C.; Yang, Jaynie F.; Basso, D. Michele; Gorassini, Monica A.

2017-01-01

Abstract Restoration of walking ability is an area of great interest in the rehabilitation of persons with spinal cord injury. Because many cortical, subcortical, and spinal neural centers contribute to locomotor function, it is important that intervention strategies be designed to target neural elements at all levels of the neuraxis that are important for walking ability. While to date most strategies have focused on activation of spinal circuits, more recent studies are investigating the value of engaging supraspinal circuits. Despite the apparent potential of pharmacological, biological, and genetic approaches, as yet none has proved more effective than physical therapeutic rehabilitation strategies. By making optimal use of the potential of the nervous system to respond to training, strategies can be developed that meet the unique needs of each person. To complement the development of optimal training interventions, it is valuable to have the ability to predict future walking function based on early clinical presentation, and to forecast responsiveness to training. A number of clinical prediction rules and association models based on common clinical measures have been developed with the intent, respectively, to predict future walking function based on early clinical presentation, and to delineate characteristics associated with responsiveness to training. Further, a number of variables that are correlated with walking function have been identified. Not surprisingly, most of these prediction rules, association models, and correlated variables incorporate measures of volitional lower extremity strength, illustrating the important influence of supraspinal centers in the production of walking behavior in humans. PMID:27673569

Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates

PubMed Central

Friedli, Lucia; Rosenzweig, Ephron S.; Barraud, Quentin; Schubert, Martin; Dominici, Nadia; Awai, Lea; Nielson, Jessica L.; Musienko, Pavel; Nout-Lomas, Yvette; Zhong, Hui; Zdunowski, Sharon; Roy, Roland R.; Strand, Sarah C.; van den Brand, Rubia; Havton, Leif A.; Beattie, Michael S.; Bresnahan, Jacqueline C.; Bézard, Erwan; Bloch, Jocelyne; Edgerton, V. Reggie; Ferguson, Adam R.; Curt, Armin; Tuszynski, Mark H.; Courtine, Grégoire

2017-01-01

Experimental and clinical studies suggest that primate species exhibit greater recovery after lateralized compared to symmetrical spinal cord injuries. Although this observation has major implications for designing clinical trials and translational therapies, advantages in recovery of nonhuman primates over other species has not been shown statistically to date, nor have the associated repair mechanisms been identified. We monitored recovery in more than 400 quadriplegic patients and found that that functional gains increased with the laterality of spinal cord damage. Electrophysiological analyses suggested that corticospinal tract reorganization contributes to the greater recovery after lateralized compared with symmetrical injuries. To investigate underlying mechanisms, we modeled lateralized injuries in rats and monkeys using a lateral hemisection, and compared anatomical and functional outcomes with patients who suffered similar lesions. Standardized assessments revealed that monkeys and humans showed greater recovery of locomotion and hand function than rats. Recovery correlated with the formation of corticospinal detour circuits below the injury, which were extensive in monkeys, but nearly absent in rats. Our results uncover pronounced inter-species differences in the nature and extent of spinal cord repair mechanisms, likely resulting from fundamental differences in the anatomical and functional characteristics of the motor systems in primates versus rodents. Although rodents remain essential for advancing regenerative therapies, the unique response of the primate corticospinal tract after injury re-emphasizes the importance of primate models for designing clinically relevant treatments. PMID:26311729

Firing patterns of spontaneously active motor units in spinal cord-injured subjects.

PubMed

Zijdewind, Inge; Thomas, Christine K

2012-04-01

Involuntary motor unit activity at low rates is common in hand muscles paralysed by spinal cord injury. Our aim was to describe these patterns of motor unit behaviour in relation to motoneurone and motor unit properties. Intramuscular electromyographic activity (EMG), surface EMG and force were recorded for 30 min from thenar muscles of nine men with chronic cervical SCI. Motor units fired for sustained periods (>10 min) at regular (coefficient of variation ≤ 0.15, CV, n =19 units) or irregular intervals (CV>0.15, n =14). Regularly firing units started and stopped firing independently suggesting that intrinsic motoneurone properties were important for recruitment and derecruitment. Recruitment (3.6 Hz, SD 1.2), maximal (10.2 Hz, SD 2.3, range: 7.5-15.4 Hz) and derecruitment frequencies were low (3.3 Hz, SD 1.6), as were firing rate increases after recruitment (~20 intervals in 3 s). Once active, firing often covaried, promoting the idea that units received common inputs.Half of the regularly firing units showed a very slow decline (>40 s) in discharge before derecruitment and had interspike intervals longer than their estimated after hyperpolarisation potential (AHP) duration (estimated by death rate and breakpoint analyses). The other units were derecruited more abruptly and had shorter estimated AHP durations. Overall, regularly firing units had longer estimated AHP durations and were weaker than irregularly firing units, suggesting they were lower threshold units. Sustained firing of units at regular rates may reflect activation of persistent inward currents, visible here in the absence of voluntary drive, whereas irregularly firing units may only respond to synaptic noise.

Spinal Cord Injury Model Systems: Review of Program and National Database From 1970 to 2015.

PubMed

Chen, Yuying; DeVivo, Michael J; Richards, J Scott; SanAgustin, Theresa B

2016-10-01

The Spinal Cord Injury Model Systems (SCIMS) centers have provided continuous, comprehensive multidisciplinary care for persons with spinal cord injury (SCI) in the United States since their inception in 1970. In addition, the research conducted and the analysis of data collected at these centers facilitate advances in the care and the overall quality of life for people with SCI. Over the past 45 years, the SCIMS program and National Spinal Cord Injury Database (NSCID) have undergone major revisions, which must be recognized in the planning, conduct, and interpretation of SCIMS research to prevent misinterpretation of findings. Therefore, we provide herein a brief review of the SCIMS program and the associated NSCID throughout its history, emphasizing changes and accomplishments within the past 15 years, to facilitate a better understanding and interpretation of the data presented in SCIMS research publications, including the articles published in this special issue of the Archives. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on Functional Recovery after Spinal Cord Injury

DTIC Science & Technology

2013-10-01

of this award, we have found that stretching negatively influences locomotor function in animals with both acute (within days) and chronic (after 3...stretching is stopped, and both acute and chronic animals show a similar time course of recovery. Finally, in very preliminary studies, we have found...glove, data acquisition system and software work very well. The results demonstrate that forces about the ankle of the rat during therapeutic

Design and criteria of electrospun fibrous scaffolds for the treatment of spinal cord injury

PubMed Central

Vigani, Barbara; Rossi, Silvia; Sandri, Giuseppina; Bonferoni, Maria Cristina; Ferrari, Franca

2017-01-01

The complex pathophysiology of spinal cord injury may explain the current lack of an effective therapeutic approach for the regeneration of damaged neuronal cells and the recovery of motor functions. Many efforts have been performed to design and develop suitable scaffolds for spinal cord regeneration, keeping in mind that the reconstruction of a pro-regenerative environment is the key challenge for an effective neurogenesis. The aim of this review is to outline the main features of an ideal scaffold, based on biomaterials, produced by the electrospinning technique and intended for the spinal cord regeneration. An overview of the polymers more investigated in the production of neural fibrous scaffolds is also provided. PMID:29239316

IGF-1 delivery to CNS attenuates motor neuron cell death but does not improve motor function in type III SMA mice.

PubMed

Tsai, Li-Kai; Chen, Yi-Chun; Cheng, Wei-Cheng; Ting, Chen-Hung; Dodge, James C; Hwu, Wuh-Liang; Cheng, Seng H; Passini, Marco A

2012-01-01

The efficacy of administering a recombinant adeno-associated virus (AAV) vector encoding human IGF-1 (AAV2/1-hIGF-1) into the deep cerebellar nucleus (DCN) of a type III SMA mouse model was evaluated. High levels of IGF-1 transcripts and protein were detected in the spinal cord at 2 months post-injection demonstrating that axonal connections between the cerebellum and spinal cord were able to act as conduits for the viral vector and protein to the spinal cord. Mice treated with AAV2/1-hIGF-1 and analyzed 8 months later showed changes in endogenous Bax and Bcl-xl levels in spinal cord motor neurons that were consistent with IGF-1-mediated anti-apoptotic effects on motor neurons. However, although AAV2/1-hIGF-1 treatment reduced the extent of motor neuron cell death, the majority of rescued motor neurons were non-functional, as they lacked axons that innervated the muscles. Furthermore, treated SMA mice exhibited abnormal muscle fibers, aberrant neuromuscular junction structure, and impaired performance on motor function tests. These data indicate that although CNS-directed expression of IGF-1 could reduce motor neuron cell death, this did not translate to improvements in motor function in an adult mouse model of type III SMA. Copyright © 2011 Elsevier Inc. All rights reserved.

Convergence of pattern generator outputs on a common mechanism of diaphragm motor unit recruitment

PubMed Central

Mantilla, Carlos B.; Seven, Yasin B.; Sieck, Gary C.

2014-01-01

Motor units are the final element of neuromotor control. In manner analogous to the organization of neuromotor control in other skeletal muscles, diaphragm motor units comprise phrenic motoneurons located in the cervical spinal cord that innervate the diaphragm muscle, the main inspiratory muscle in mammals. Diaphragm motor units play a primary role in sustaining ventilation, but are also active in other non-ventilatory behaviors, including coughing, sneezing, vomiting, defecation and parturition. Diaphragm muscle fibers comprise all fiber types. Thus, diaphragm motor units display substantial differences in contractile and fatigue properties, but importantly properties of the motoneuron and muscle fibers within a motor unit are matched. As in other skeletal muscles, diaphragm motor units are recruited in order such that motor units that display greater fatigue resistance are recruited earlier and more often than more fatigable motor units. The properties of the motor unit population are critical determinants of the function of a skeletal muscle across the range of possible motor tasks. Accordingly, fatigue-resistant motor units are sufficient to generate the forces necessary for ventilatory behaviors whereas more fatigable units are only activated during expulsive behaviors important for airway clearance. Neuromotor control of diaphragm motor units may reflect selective inputs from distinct pattern generators distributed according to the motor unit properties necessary to accomplish these different motor tasks. In contrast, widely-distributed inputs to phrenic motoneurons from various pattern generators (e.g., for breathing, coughing or vocalization) would dictate recruitment order based on intrinsic electrophysiological properties. PMID:24746055

NORADRENERGIC INNERVATION OF THE RAT SPINAL CORD CAUDAL TO A COMPLETE SPINAL CORD TRANSECTION: EFFECTS OF OLFACTORY ENSHEATHING GLIA

PubMed Central

Takeoka, Aya; Kubasak, Marc D.; Zhong, Hui; Kaplan, Jennifer; Roy, Roland R.; Phelps, Patricia E.

2010-01-01

Transplantation of olfactory bulb-derived olfactory ensheathing glia (OEG) combined with step training improves hindlimb locomotion in adult rats with a complete spinal cord transection. Spinal cord injury studies use the presence of noradrenergic (NA) axons caudal to the injury site as evidence of axonal regeneration and we previously found more NA axons just caudal to the transection in OEG- than media-injected spinal rats. We therefore hypothesized that OEG transplantation promotes descending coeruleospinal regeneration that contributes to the recovery of hindlimb locomotion. Now we report that NA axons are present throughout the caudal stump of both media- and OEG-injected spinal rats and they enter the spinal cord from the periphery via dorsal and ventral roots and along large penetrating blood vessels. These results indicate that the presence of NA fibers in the caudal spinal cord is not a reliable indicator of coeruleospinal regeneration. We then asked if NA axons appose cholinergic neurons associated with motor functions, i.e., central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more NA varicosities adjacent to central canal cluster cells, partition cells, and SMNs in the lumbar enlargement of OEG- than media-injected rats. As non-synaptic release of NA is common in the spinal cord, more associations between NA varicosities and motor-associated cholinergic neurons in the lumbar spinal cord may contribute to the improved treadmill stepping observed in OEG-injected spinal rats. This effect could be mediated through direct association with SMNs and/or indirectly via cholinergic interneurons. PMID:20025875

Clinical, magnetic resonance imaging, and histopathologic findings in 6 dogs with surgically resected extraparenchymal spinal cord hematomas.

PubMed

Hague, D W; Joslyn, S; Bush, W W; Glass, E N; Durham, A C

2015-01-01

Extraparenchymal spinal cord hematoma has been described in veterinary medicine in association with neoplasia, intervertebral disk disease, and snake envenomation. There are rare reports of spontaneous extraparenchymal spinal cord hematoma formation with no known cause in human medicine. Multiple cases of spontaneous extraparenchymal spinal cord hematoma have not been described previously in veterinary medicine. To describe the signalment, clinical findings, magnetic resonance imaging (MRI) features, and surgical outcomes in histopathologically confirmed extraparenchymal spinal cord hematomas in dogs with no identified underlying etiology. Six dogs had MRI of the spinal cord, decompressive spinal surgery, and histopathologic confirmation of extraparenchymal spinal cord hematoma not associated with an underlying cause. Multi-institutional retrospective study. Six patients had spontaneous extraparenchymal spinal cord hematoma formation. MRI showed normal signal within the spinal cord parenchyma in all patients. All hematomas had T2-weighted hyperintensity and the majority (5/6) had no contrast enhancement. All dogs underwent surgical decompression and most patients (5/6) returned to normal or near normal neurologic function postoperatively. Follow-up of the patients (ranging between 921 and 1,446 days) showed no progression of neurologic clinical signs or any conditions associated with increased bleeding tendency. Before surgery and histopathology confirming extraparenchymal hematoma, the primary differential in most cases was neoplasia, based on the MRI findings. This retrospective study reminds clinicians of the importance of the combination of advanced imaging combined with histopathologic diagnosis. The prognosis for spontaneous spinal cord extraparenchymal hematoma with surgical decompression appears to be favorable in most cases. Copyright © 2015 by the American College of Veterinary Internal Medicine.

Retraining the injured spinal cord

NASA Technical Reports Server (NTRS)

Edgerton, V. R.; Leon, R. D.; Harkema, S. J.; Hodgson, J. A.; London, N.; Reinkensmeyer, D. J.; Roy, R. R.; Talmadge, R. J.; Tillakaratne, N. J.; Timoszyk, W.;

Sexual Counseling with Spinal Cord-Injured Clients

ERIC Educational Resources Information Center

Miller, Donald K.

1975-01-01

Spinal cord-injured clients have many fears and misapprehensions about their sexual functioning. Such misapprehensions can be helped by the counselor's willingness to discuss sexual issues openly. Clients need a clear and accurate picture of the facts, as well as encouragement and support to help them rediscover their sexuality. (Author)

Aging among the Disabled: A Neglected Area.

ERIC Educational Resources Information Center

Kemp, Bryan

The paper addresses issues involved in the aging of persons disabled earlier through spinal dysfunction (post-polio and spinal cord injury) and mental retardation. Biological, psychological, and social aspects of aging are examined separately. In a discussion of longevity and physical health, causes of functional aging are considered.…

Enrichment of spinal cord cell cultures with motoneurons

PubMed Central

1978-01-01

Spinal cord cell cultures contain several types of neurons. Two methods are described for enriching such cultures with motoneurons (defined here simply as cholinergic cells that are capable of innervating muscle). In the first method, 7-day embryonic chick spinal cord neurons were separated according to size by 1 g velocity sedimentation. It is assumed that cholinergic motoneurons are among the largest cells present at this stage. The spinal cords were dissociated vigorously so that 95-98% of the cells in the initial suspension were isolated from one another. Cells in leading fractions (large cell fractions: LCFs) contain about seven times as much choline acetyltransferase (CAT) activity per unit cytoplasm as do cells in trailing fractions (small cell fractions: SCFs). Muscle cultures seeded with LCFs develop 10-70 times as much CAT as cultures seeded with SCFs and six times as much CAT as cultures seeded with control (unfractionated) spinal cord cells. More than 20% of the large neurons in LCF-muscle cultures innervate nearby myotubes. In the second method, neurons were gently dissociated from 4-day embryonic spinal cords and maintained in vitro. This approach is based on earlier observations that cholinergic neurons are among the first cells to withdraw form the mitotic cycle in the developing chick embryo (Hamburger, V. 1948. J. Comp. Neurol. 88:221- 283; and Levi-Montalcini, R. 1950. J. Morphol. 86:253-283). 4-Day spinal cord-muscle cultures develop three times as much CAT as do 7-day spinal cord-muscle plates, prepared in the same (gentle) manner. More than 50% of the relatively large 4-day neurons innervate nearby myotubes. Thus, both methods are useful first steps toward the complete isolation of motoneurons. Both methods should facilitate study of the development of cholinergic neurons and of nerve-muscle synapse formation. PMID:566275

Different phase delays of peripheral input to primate motor cortex and spinal cord promote cancellation at physiological tremor frequencies

PubMed Central

Koželj, Saša

2014-01-01

Neurons in the spinal cord and motor cortex (M1) are partially phase-locked to cycles of physiological tremor, but with opposite phases. Convergence of spinal and cortical activity onto motoneurons may thus produce phase cancellation and a reduction in tremor amplitude. The mechanisms underlying this phase difference are unknown. We investigated coherence between spinal and M1 activity with sensory input. In two anesthetized monkeys, we electrically stimulated the medial, ulnar, deep radial, and superficial radial nerves; stimuli were timed as independent Poisson processes (rate 10 Hz). Single units were recorded from M1 (147 cells) or cervical spinal cord (61 cells). Ninety M1 cells were antidromically identified as pyramidal tract neurons (PTNs); M1 neurons were additionally classified according to M1 subdivision (rostral/caudal, M1r/c). Spike-stimulus coherence analysis revealed significant coupling over a broad range of frequencies, with the strongest coherence at <50 Hz. Delays implied by the slope of the coherence phase-frequency relationship were greater than the response onset latency, reflecting the importance of late response components for the transmission of oscillatory inputs. The spike-stimulus coherence phase over the 6–13 Hz physiological tremor band differed significantly between M1 and spinal cells (phase differences relative to the cord of 2.72 ± 0.29 and 1.72 ± 0.37 radians for PTNs from M1c and M1r, respectively). We conclude that different phases of the response to peripheral input could partially underlie antiphase M1 and spinal cord activity during motor behavior. The coordinated action of spinal and cortical feedback will act to reduce tremulous oscillations, possibly improving the overall stability and precision of motor control. PMID:24572094

Different phase delays of peripheral input to primate motor cortex and spinal cord promote cancellation at physiological tremor frequencies.

PubMed

Koželj, Saša; Baker, Stuart N

2014-05-01

Neurons in the spinal cord and motor cortex (M1) are partially phase-locked to cycles of physiological tremor, but with opposite phases. Convergence of spinal and cortical activity onto motoneurons may thus produce phase cancellation and a reduction in tremor amplitude. The mechanisms underlying this phase difference are unknown. We investigated coherence between spinal and M1 activity with sensory input. In two anesthetized monkeys, we electrically stimulated the medial, ulnar, deep radial, and superficial radial nerves; stimuli were timed as independent Poisson processes (rate 10 Hz). Single units were recorded from M1 (147 cells) or cervical spinal cord (61 cells). Ninety M1 cells were antidromically identified as pyramidal tract neurons (PTNs); M1 neurons were additionally classified according to M1 subdivision (rostral/caudal, M1r/c). Spike-stimulus coherence analysis revealed significant coupling over a broad range of frequencies, with the strongest coherence at <50 Hz. Delays implied by the slope of the coherence phase-frequency relationship were greater than the response onset latency, reflecting the importance of late response components for the transmission of oscillatory inputs. The spike-stimulus coherence phase over the 6-13 Hz physiological tremor band differed significantly between M1 and spinal cells (phase differences relative to the cord of 2.72 ± 0.29 and 1.72 ± 0.37 radians for PTNs from M1c and M1r, respectively). We conclude that different phases of the response to peripheral input could partially underlie antiphase M1 and spinal cord activity during motor behavior. The coordinated action of spinal and cortical feedback will act to reduce tremulous oscillations, possibly improving the overall stability and precision of motor control. Copyright © 2014 the American Physiological Society.

Mechanical design and driving mechanism of an isokinetic functional electrical stimulation-based leg stepping trainer.

PubMed

Hamzaid, N A; Fornusek, C; Ruys, A; Davis, G M

2007-12-01

The mechanical design of a constant velocity (isokinetic) leg stepping trainer driven by functional electrical stimulation-evoked muscle contractions was the focus of this paper. The system was conceived for training the leg muscles of neurologically-impaired patients. A commercially available slider crank mechanism for elliptical stepping exercise was adapted to a motorized isokinetic driving mechanism. The exercise system permits constant-velocity pedalling at cadences of 1-60 rev x min(-1). The variable-velocity feature allows low pedalling forces for individuals with very weak leg muscles, yet provides resistance to higher pedalling effort in stronger patients. In the future, the system will be integrated with a computer-controlled neuromuscular stimulator and a feedback control unit to monitor training responses of spinal cord-injured, stroke and head injury patients.

Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat.

PubMed

Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

2007-04-01

Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor kappaB (NF-kappaB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-kappaB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-kappaB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-kappaB super- repressor IkappaBalpha resulted in an inhibition of the NF-kappaB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IkappaBalpha overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-kappaB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-kappaB pathway in the development of neuropathic pain after peripheral nerve injury.

Exogenous BDNF enhances the integration of chronically injured axons that regenerate through a peripheral nerve grafted into a chondroitinase-treated spinal cord injury site

PubMed Central

Tom, Veronica J.; Sandrow-Feinberg, Harra R.; Miller, Kassi; Domitrovich, Cheryl; Bouyer, Julien; Zhukareva, Victoria; Klaw, Michelle C.; Lemay, Michel A.; Houlé, John D.

2016-01-01

Although axons lose some of their intrinsic capacity for growth after their developmental period, some axons retain the potential for regrowth after injury. When provided with a growth-promoting substrate such as a peripheral nerve graft (PNG), severed axons regenerate into and through the graft; however, they stop when they reach the glial scar at the distal graft-host interface that is rich with inhibitory chondroitin sulfate proteoglycans. We previously showed that treatment of a spinal cord injury site with chondroitinase (ChABC) allows axons within the graft to traverse the scar and reinnervate spinal cord, where they form functional synapses. While this improvement in outgrowth was significant, it still represented only a small percentage (<20%) of axons compared to the total number of axons that regenerated into the PNG. Here we tested whether providing exogenous brain-derived neurotrophic factor (BDNF) via lentivirus in tissue distal to the PNG would augment regeneration beyond a ChABC-treated glial interface. We found that ChABC treatment alone promoted axonal regeneration but combining ChABC with BDNF-lentivirus did not increase the number of axons that regenerated back into spinal cord. Combining BDNF with ChABC did increase the number of spinal cord neurons that were trans-synaptically activated during electrical stimulation of the graft, as indicated by c-Fos expression, suggesting that BDNF overexpression improved the functional significance of axons that did reinnervate distal spinal cord tissue. PMID:23022460

Impact of Spinal Manipulation on Cortical Drive to Upper and Lower Limb Muscles

PubMed Central

Haavik, Heidi; Niazi, Imran Khan; Jochumsen, Mads; Sherwin, Diane; Flavel, Stanley; Türker, Kemal S.

2016-01-01

This study investigates whether spinal manipulation leads to changes in motor control by measuring the recruitment pattern of motor units in both an upper and lower limb muscle and to see whether such changes may at least in part occur at the cortical level by recording movement related cortical potential (MRCP) amplitudes. In experiment one, transcranial magnetic stimulation input–output (TMS I/O) curves for an upper limb muscle (abductor pollicus brevis; APB) were recorded, along with F waves before and after either spinal manipulation or a control intervention for the same subjects on two different days. During two separate days, lower limb TMS I/O curves and MRCPs were recorded from tibialis anterior muscle (TA) pre and post spinal manipulation. Dependent measures were compared with repeated measures analysis of variance, with p set at 0.05. Spinal manipulation resulted in a 54.5% ± 93.1% increase in maximum motor evoked potential (MEPmax) for APB and a 44.6% ± 69.6% increase in MEPmax for TA. For the MRCP data following spinal manipulation there were significant difference for amplitude of early bereitschafts-potential (EBP), late bereitschafts potential (LBP) and also for peak negativity (PN). The results of this study show that spinal manipulation leads to changes in cortical excitability, as measured by significantly larger MEPmax for TMS induced input–output curves for both an upper and lower limb muscle, and with larger amplitudes of MRCP component post manipulation. No changes in spinal measures (i.e., F wave amplitudes or persistence) were observed, and no changes were shown following the control condition. These results are consistent with previous findings that have suggested increases in strength following spinal manipulation were due to descending cortical drive and could not be explained by changes at the level of the spinal cord. Spinal manipulation may therefore be indicated for the patients who have lost tonus of their muscle and/or are recovering from muscle degrading dysfunctions such as stroke or orthopaedic operations and/or may also be of interest to sports performers. These findings should be followed up in the relevant populations. PMID:28025542

Relationship of psychology inpatient rehabilitation services and patient characteristics to outcomes following spinal cord injury: The SCIRehab Project

PubMed Central

Heinemann, Allen W.; Wilson, Catherine S.; Huston, Toby; Koval, Jill; Gordon, Samuel; Gassaway, Julie; Kreider, Scott E.D.; Whiteneck, Gale

2012-01-01

Context and objective To evaluate the effects of psychological interventions on rehabilitation outcomes, including residence and functional status at discharge, and residence, school attendance, or employment, and physical, social, occupational, and mobility aspects of participation 1 year after spinal cord injury (SCI). Design Prospective observational cohort study. Setting Six inpatient rehabilitation facilities in the United States. Participants Inpatients with SCI 12 years of age and older. Interventions Usual rehabilitation care. Outcome measures Functional Independence Measure at rehabilitation discharge and 1-year injury anniversary; discharge destination and residence at 1-year anniversary; Craig Handicap Assessment and Reporting Technique, Diener Satisfaction with Life Scale, Patient Health Questionnaire, employment or school attendance, rehospitalization, and occurrence of a pressure ulcer at 1-year anniversary. Results More time in psycho-educational interventions was associated with better function, discharge to home, home residence at 1 year, and the absence of pressure ulcers at 1 year. More psychotherapeutic sessions focusing on processing emotions and/or locus of control were associated with poorer function at discharge and 1 year, less physical independence and community mobility, lower satisfaction with life, and the presence of pressure sores at 1 year. Conclusions Psychological services are an important component of comprehensive medical rehabilitation and tailored to patient needs and readiness to benefit from rehabilitation. Services focused on remediating deficits tend to be associated with negative outcomes, while services intended to foster adjustment and growth tend to be associated with favorable outcomes. Further research is needed to determine the optimal type and timing of psychological services during inpatient rehabilitation based on individuals' strengths and vulnerabilities. Note This is the sixth in this third series of SCIRehab articles. PMID:23318038

Emergence of Serotonergic Neurons After Spinal Cord Injury in Turtles

PubMed Central

Fabbiani, Gabriela; Rehermann, María I.; Aldecosea, Carina; Trujillo-Cenóz, Omar; Russo, Raúl E.

2018-01-01

Plasticity of neural circuits takes many forms and plays a fundamental role in regulating behavior to changing demands while maintaining stability. For example, during spinal cord development neurotransmitter identity in neurons is dynamically adjusted in response to changes in the activity of spinal networks. It is reasonable to speculate that this type of plasticity might occur also in mature spinal circuits in response to injury. Because serotonergic signaling has a central role in spinal cord functions, we hypothesized that spinal cord injury (SCI) in the fresh water turtle Trachemys scripta elegans may trigger homeostatic changes in serotonergic innervation. To test this possibility we performed immunohistochemistry for serotonin (5-HT) and key molecules involved in the determination of the serotonergic phenotype before and after SCI. We found that as expected, in the acute phase after injury the dense serotonergic innervation was strongly reduced. However, 30 days after SCI the population of serotonergic cells (5-HT+) increased in segments caudal to the lesion site. These cells expressed the neuronal marker HuC/D and the transcription factor Nkx6.1. The new serotonergic neurons did not incorporate the thymidine analog 5-bromo-2′-deoxyuridine (BrdU) and did not express the proliferating cell nuclear antigen (PCNA) indicating that novel serotonergic neurons were not newborn but post-mitotic cells that have changed their neurochemical identity. Switching towards a serotonergic neurotransmitter phenotype may be a spinal cord homeostatic mechanism to compensate for the loss of descending serotonergic neuromodulation, thereby helping the outstanding functional recovery displayed by turtles. The 5-HT1A receptor agonist (±)-8-Hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT) blocked the increase in 5-HT+ cells suggesting 5-HT1A receptors may trigger the respecification process. PMID:29593503

Photothrombosis-induced Focal Ischemia as a Model of Spinal Cord Injury in Mice

PubMed Central

Zhang, Nannan; Ding, Shinghua

2015-01-01

Spinal cord injury (SCI) is a devastating clinical condition causing permanent changes in sensorimotor and autonomic functions of the spinal cord (SC) below the site of injury. The secondary ischemia that develops following the initial mechanical insult is a serious complication of the SCI and severely impairs the function and viability of surviving neuronal and non-neuronal cells in the SC. In addition, ischemia is also responsible for the growth of lesion during chronic phase of injury and interferes with the cellular repair and healing processes. Thus there is a need to develop a spinal cord ischemia model for studying the mechanisms of ischemia-induced pathology. Focal ischemia induced by photothrombosis (PT) is a minimally invasive and very well established procedure used to investigate the pathology of ischemia-induced cell death in the brain. Here, we describe the use of PT to induce an ischemic lesion in the spinal cord of mice. Following retro-orbital sinus injection of Rose Bengal, the posterior spinal vein and other capillaries on the dorsal surface of SC were irradiated with a green light resulting in the formation of a thrombus and thus ischemia in the affected region. Results from histology and immunochemistry studies show that PT-induced ischemia caused spinal cord infarction, loss of neurons and reactive gliosis. Using this technique a highly reproducible and relatively easy model of SCI in mice can be achieved that would serve the purpose of scientific investigations into the mechanisms of ischemia induced cell death as well as the efficacy of neuroprotective drugs. This model will also allow exploration of the pathological changes that occur following SCI in live mice like axonal degeneration and regeneration, neuronal and astrocytic Ca2+ signaling using two-photon microscopy. PMID:26274772

Development of less invasive neuromuscular electrical stimulation model for motor therapy in rodents

PubMed Central

Kanchiku, Tsukasa; Kato, Yoshihiko; Suzuki, Hidenori; Imajo, Yasuaki; Yoshida, Yuichiro; Moriya, Atsushi; Taguchi, Toshihiko; Jung, Ranu

2012-01-01

Background Combination therapy is essential for functional repairs of the spinal cord. Rehabilitative therapy can be considered as the key for reorganizing the nervous system after spinal cord regeneration therapy. Functional electrical stimulation has been used as a neuroprosthesis in quadriplegia and can be used for providing rehabilitative therapy to tap the capability for central nervous system reorganization after spinal cord regeneration therapy. Objective To develop a less invasive muscular electrical stimulation model capable of being combined with spinal cord regeneration therapy especially for motor therapy in the acute stage after spinal cord injury. Methods The tibialis anterior and gastrocnemius motor points were identified in intact anesthetized adult female Fischer rats, and stimulation needle electrodes were percutaneously inserted into these points. Threshold currents for visual twitches were obtained upon stimulation using pulses of 75 or 8 kHz for 200 ms. Biphasic pulse widths of 20, 40, 80, 100, 300, and 500 µs per phase were used to determine strength–duration curves. Using these parameters and previously obtained locomotor electromyogram data, stimulations were performed on bilateral joint muscle pairs to produce reciprocal flexion/extension movements of the ankle for 15 minutes while three-dimensional joint kinematics were assessed. Results Rhythmic muscular electrical stimulation with needle electrodes was successfully done, but decreased range of motion (ROM) over time. High-frequency and high-amplitude stimulation was also shown to be effective in alleviating decreases in ROM due to muscle fatigue. Conclusions This model will be useful for investigating the ability of rhythmic muscular electrical stimulation therapy to promote motor recovery, in addition to the efficacy of combining treatments with spinal cord regeneration therapy after spinal cord injuries. PMID:22507026

Cervical intraspinal microstimulation evokes robust forelimb movements before and after injury

NASA Astrophysics Data System (ADS)

Sunshine, Michael D.; Cho, Frances S.; Lockwood, Danielle R.; Fechko, Amber S.; Kasten, Michael R.; Moritz, Chet T.

2013-06-01

Objective. Intraspinal microstimulation (ISMS) is a promising method for reanimating paralyzed limbs following neurological injury. ISMS within the cervical and lumbar spinal cord is capable of evoking a variety of highly-functional movements prior to injury, but the ability of ISMS to evoke forelimb movements after cervical spinal cord injury is unknown. Here we examine the forelimb movements and muscles activated by cervical ISMS both before and after contusion injury. Approach. We documented the forelimb muscles activated and movements evoked via systematic stimulation of the rodent cervical spinal cord both before injury and three, six and nine weeks following a moderate C4/C5 lateralized contusion injury. Animals were anesthetized with isoflurane to permit construction of somatotopic maps of evoked movements and quantify evoked muscle synergies between cervical segments C3 and T1. Main results. When ISMS was delivered to the cervical spinal cord, a variety of responses were observed at 68% of locations tested, with a spatial distribution that generally corresponded to the location of motor neuron pools. Stimulus currents required to achieve movement and the number of sites where movements could be evoked were unchanged by spinal cord injury. A transient shift toward extension-dominated movements and restricted muscle synergies were observed at three and six weeks following injury, respectively. By nine weeks after injury, however, ISMS-evoked patterns were similar to spinally-intact animals. Significance. The results demonstrate the potential for cervical ISMS to reanimate hand and arm function following spinal cord injury. Robust forelimb movements can be evoked both before and during the chronic stages of recovery from a clinically relevant and sustained cervical contusion injury.

Protocol of a prospective cohort study of the effect of different methods of drainage of neuropathic bladder on occurrence of symptomatic urinary infection, and adverse events related to the urinary drainage system in spinal cord injury patients

PubMed Central

Vaidyanathan, Subramanian; Soni, Bhakul M; Gurpreet, Singh; Mansour, Paul; Hughes, Peter L; Oo, Tun; Sett, Pradipkumar; Parsons, Keith F; Davies, John C

2001-01-01

Background To present a protocol of a prospective, cohort study in which four groups of spinal cord injury (SCI) patients will participate. (Patients with indwelling urethral catheter; patients who perform intermittent catheterisation without wearing a penile sheath; patients who perform intermittent catheterisation and wear penile sheath as well; and patients with penile sheath drainage). Objectives (1) What is the incidence of symptomatic urinary infection in men with spinal cord injury who use different types of bladder drainage? (2) Which are predisposing factors for the occurrence of symptomatic urinary infection in men with spinal cord injury who practise different methods of bladder drainage? (3) What is the incidence of catheter and urinary drainage system-related adverse events in the four groups of SCI patients? Patients The criteria for inclusion are as follow: (1) Male patients with neuropathic bladder due to spinal cord injury, who are registered with the Regional Spinal Injuries Centre, Southport, England. (2) Age: 18 years or above. (3) Patients who are willing to give informed consent for participation in the study. (4) Patients willing to be contacted every two weeks by a staff of the spinal unit for 36 months. (5) Patients who are willing to maintain an accurate record of adverse events related to urinary catheter and urinary drainage system and predisposing factors for the occurrence of symptomatic urinary infection. (6) Patients, who are stabilised in a particular method of bladder drainage, and therefore, unlikely to make a permanent change in the method of bladder drainage (e.g. from penile sheath drainage to the use of long-term indwelling catheter) during a foreseeable future. Methods The participants will be observed for a period of 36 months. A staff of the spinal injuries unit will contact the participants by telephone every two weeks on a mutually agreed day and time. The information obtained during this standardised telephonic interview conducted once in two weeks will be entered in a database. When a participant develops symptom(s) suggestive of urinary infection, he will undergo urine and blood tests, and imaging studies of the urinary tract. Conclusion This study will provide information regarding the occurrence of symptomatic urinary infection, predisposing factors for development of urinary infection, and adverse events related to urinary catheter and urinary drainage system in SCI patients using different methods of bladder drainage. PMID:11734072

In-vivo spinal cord deformation in flexion

NASA Astrophysics Data System (ADS)

Yuan, Qing; Dougherty, Lawrence; Margulies, Susan S.

1997-05-01

Traumatic mechanical loading of the head-neck complex results cervical spinal cord injury when the distortion of the cord is sufficient to produce functional or structural failure of the cord's neural and/or vascular components. Characterizing cervical spinal cord deformation during physiological loading conditions is an important step to defining a comprehensive injury threshold associated with acute spinal cord injury. In this study, in vivo quasi- static deformation of the cervical spinal cord during flexion of the neck in human volunteers was measured using magnetic resonance (MR) imaging of motion with spatial modulation of magnetization (SPAMM). A custom-designed device was built to guide the motion of the neck and enhance more reproducibility. the SPAMM pulse sequence labeled the tissue with a series of parallel tagging lines. A single- shot gradient-recalled-echo sequence was used to acquire the mid-sagittal image of the cervical spine. A comparison of the tagged line pattern in each MR reference and deformed image pair revealed the distortion of the spinal cord. The results showed the cervical spinal cord elongates during head flexion. The elongation experienced by the spinal cord varies linearly with head flexion, with the posterior surface of the cord stretching more than the anterior surface. The maximal elongation of the cord is about 12 percent of its original length.

Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury.

PubMed

Hubscher, Charles H; Herrity, April N; Williams, Carolyn S; Montgomery, Lynnette R; Willhite, Andrea M; Angeli, Claudia A; Harkema, Susan J

2018-01-01

Locomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs' pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury). Prospective cohort study; pilot trial with small sample size. Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart. Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants. These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions. ClinicalTrials.gov NCT03036527.

Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury

PubMed Central

Williams, Carolyn S.; Montgomery, Lynnette R.; Willhite, Andrea M.; Angeli, Claudia A.; Harkema, Susan J.

2018-01-01

Objective Locomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs’ pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury). Study design Prospective cohort study; pilot trial with small sample size. Methods Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart. Results Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants. Conclusions These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions. Trial registration ClinicalTrials.gov NCT03036527 PMID:29385166

Recovery of storage and emptying functions of the urinary bladder after spinal anesthesia with lidocaine and with bupivacaine in men.

PubMed

Kamphuis, E T; Ionescu, T I; Kuipers, P W; de Gier, J; van Venrooij, G E; Boon, T A

1998-02-01

The aim of this study was to evaluate and compare the effects of spinal anesthesia with lidocaine and with bupivacaine on urinary bladder function in healthy men who were scheduled for minor orthopaedic surgical procedures. Twenty men were randomly allocated to receive either bupivacaine or lidocaine. Before spinal anesthesia, filling cystometry was performed with the patient in the supine position and a pressure flow study was done with the patient in the standing position. After operation, cystometric measurements were continued until the patient could void urine spontaneously. The levels of analgesia and of motor blockade were recorded. The urge to void disappeared immediately after injection of the local anesthetics. There was no difference in the duration of lower extremity motor blockade between bupivacaine and lidocaine. Detrusor blockade lasted significantly longer in the bupivacaine group (means +/- SD, 460 +/- 60 min) than in the lidocaine group (235 +/- 30 min). Total fluid intake and urine volume accumulated during the detrusor blockade were significantly higher in the bupivacaine group than in the lidocaine group. In the bupivacaine group, the total volume of accumulated urine (875 +/- 385 ml) was also significantly higher than cystometric bladder capacity (505 +/- 120 ml) with the risk of over distension of the bladder. Spontaneous voiding of urine did not occur until segmental sensory analgesia had regressed to the third sacral segment. Spinal anesthesia with lidocaine and with bupivacaine causes a clinically significant disturbance of bladder function due to interruption of the micturition reflex. The urge to void disappears quickly and bladder function remains impaired until the block has regressed to the third sacral segment in all patients. With long-acting local anesthetics, the volume of accumulated urine may exceed the cystometric bladder capacity. With respect to recovery of urinary bladder function, the use of short-acting local anesthetics for spinal anesthesia seems to be preferable.

Transcranial direct current stimulation (tDCS) of the primary motor cortex and robot-assisted arm training in chronic incomplete cervical spinal cord injury: A proof of concept sham-randomized clinical study.

PubMed

Yozbatiran, Nuray; Keser, Zafer; Davis, Matthew; Stampas, Argyrios; O'Malley, Marcia K; Cooper-Hay, Catherine; Frontera, Joel; Fregni, Felipe; Francisco, Gerard E

2016-07-15

After cervical spinal cord injury, current options for treatment of upper extremity motor functions have been limited to traditional approaches. However, there is a substantial need to explore more rigorous alternative treatments to facilitate motor recovery. To demonstrate whether anodal-primary motor cortex (M1) excitability enhancement (with cathodal-supra orbital area) (atDCS) combined with robot-assisted arm training (R-AAT) will provide greater improvement in contralateral arm and hand motor functions compared to sham stimulation (stDCS) and R-AAT in patients with chronic, incomplete cervical spinal cord injury (iCSCI). In this parallel-group, double-blinded, randomized and sham-controlled trial, nine participants with chronic iCSCI (AIS C and D level) were randomized to receive 10 sessions of atDCS or stDSC combined with R-AAT. Feasibility and tolerability was assessed with attrition rate and occurrence of adverse events, Changes in arm and hand function were assessed with Jebson Taylor Hand Function Test (JTHFT). Amount of Use Scale of Motor Activity Log (AOU-MAL), American Spinal Injury Association Upper Extremity Motor Score and Modified Ashworth Scale (MAS) at baseline, after treatment, and at two-month follow-up. None of the participants missed a treatment session or dropped-out due to adverse events related to the treatment protocol. Participants tended to perform better in JTHFT and AOU-MAL after treatment. Active group at post-treatment and two-month follow-up demonstrated better arm and hand performance compared to sham group. These preliminary findings support that modulating excitatory input of the corticospinal tracts on spinal circuits may be a promising strategy in improving arm and hand functions in persons with incomplete tetraplegia. Further study is needed to explore the underlying mechanisms of recovery.

A Brain-Machine-Muscle Interface for Restoring Hindlimb Locomotion after Complete Spinal Transection in Rats

PubMed Central

Alam, Monzurul; Chen, Xi; Zhang, Zicong; Li, Yan; He, Jufang

2014-01-01

A brain-machine interface (BMI) is a neuroprosthetic device that can restore motor function of individuals with paralysis. Although the feasibility of BMI control of upper-limb neuroprostheses has been demonstrated, a BMI for the restoration of lower-limb motor functions has not yet been developed. The objective of this study was to determine if gait-related information can be captured from neural activity recorded from the primary motor cortex of rats, and if this neural information can be used to stimulate paralysed hindlimb muscles after complete spinal cord transection. Neural activity was recorded from the hindlimb area of the primary motor cortex of six female Sprague Dawley rats during treadmill locomotion before and after mid-thoracic transection. Before spinal transection there was a strong association between neural activity and the step cycle. This association decreased after spinal transection. However, the locomotive state (standing vs. walking) could still be successfully decoded from neural recordings made after spinal transection. A novel BMI device was developed that processed this neural information in real-time and used it to control electrical stimulation of paralysed hindlimb muscles. This system was able to elicit hindlimb muscle contractions that mimicked forelimb stepping. We propose this lower-limb BMI as a future neuroprosthesis for human paraplegics. PMID:25084446

A brain-machine-muscle interface for restoring hindlimb locomotion after complete spinal transection in rats.

PubMed

Alam, Monzurul; Chen, Xi; Zhang, Zicong; Li, Yan; He, Jufang

2014-01-01

A brain-machine interface (BMI) is a neuroprosthetic device that can restore motor function of individuals with paralysis. Although the feasibility of BMI control of upper-limb neuroprostheses has been demonstrated, a BMI for the restoration of lower-limb motor functions has not yet been developed. The objective of this study was to determine if gait-related information can be captured from neural activity recorded from the primary motor cortex of rats, and if this neural information can be used to stimulate paralysed hindlimb muscles after complete spinal cord transection. Neural activity was recorded from the hindlimb area of the primary motor cortex of six female Sprague Dawley rats during treadmill locomotion before and after mid-thoracic transection. Before spinal transection there was a strong association between neural activity and the step cycle. This association decreased after spinal transection. However, the locomotive state (standing vs. walking) could still be successfully decoded from neural recordings made after spinal transection. A novel BMI device was developed that processed this neural information in real-time and used it to control electrical stimulation of paralysed hindlimb muscles. This system was able to elicit hindlimb muscle contractions that mimicked forelimb stepping. We propose this lower-limb BMI as a future neuroprosthesis for human paraplegics.

A neural circuitry that emphasizes spinal feedback generates diverse behaviours of human locomotion

PubMed Central

Song, Seungmoon; Geyer, Hartmut

2015-01-01

Neural networks along the spinal cord contribute substantially to generating locomotion behaviours in humans and other legged animals. However, the neural circuitry involved in this spinal control remains unclear. We here propose a specific circuitry that emphasizes feedback integration over central pattern generation. The circuitry is based on neurophysiologically plausible muscle-reflex pathways that are organized in 10 spinal modules realizing limb functions essential to legged systems in stance and swing. These modules are combined with a supraspinal control layer that adjusts the desired foot placements and selects the leg that is to transition into swing control during double support. Using physics-based simulation, we test the proposed circuitry in a neuromuscular human model that includes neural transmission delays, musculotendon dynamics and compliant foot–ground contacts. We find that the control network is sufficient to compose steady and transitional 3-D locomotion behaviours including walking and running, acceleration and deceleration, slope and stair negotiation, turning, and deliberate obstacle avoidance. The results suggest feedback integration to be functionally more important than central pattern generation in human locomotion across behaviours. In addition, the proposed control architecture may serve as a guide in the search for the neurophysiological origin and circuitry of spinal control in humans. PMID:25920414

Robust prediction of three-dimensional spinal curve from back surface for non-invasive follow-up of scoliosis

NASA Astrophysics Data System (ADS)

Bergeron, Charles; Labelle, Hubert; Ronsky, Janet; Zernicke, Ronald

2005-04-01

Spinal curvature progression in scoliosis patients is monitored from X-rays, and this serial exposure to harmful radiation increases the incidence of developing cancer. With the aim of reducing the invasiveness of follow-up, this study seeks to relate the three-dimensional external surface to the internal geometry, having assumed that that the physiological links between these are sufficiently regular across patients. A database was used of 194 quasi-simultaneous acquisitions of two X-rays and a 3D laser scan of the entire trunk. Data was processed to sets of datapoints representing the trunk surface and spinal curve. Functional data analyses were performed using generalized Fourier series using a Haar basis and functional minimum noise fractions. The resulting coefficients became inputs and outputs, respectively, to an array of support vector regression (SVR) machines. SVR parameters were set based on theoretical results, and cross-validation increased confidence in the system's performance. Predicted lateral and frontal views of the spinal curve from the back surface demonstrated average L2-errors of 6.13 and 4.38 millimetres, respectively, across the test set; these compared favourably with measurement error in data. This constitutes a first robust prediction of the 3D spinal curve from external data using learning techniques.

Effects of aquaporin 4 and inward rectifier potassium channel 4.1 on medullospinal edema after methylprednisolone treatment to suppress acute spinal cord injury in rats.

PubMed

Li, Ye; Hu, Haifeng; Liu, Jingchen; Zhu, Qingsan; Gu, Rui

2018-02-01

To investigate the effects of aquaporin 4 (AQP4) and inward rectifier potassium channel 4.1 (Kir4.1) on medullospinal edema after treatment with methylprednisolone (MP) to suppress acute spinal cord injury (ASCI) in rats. Sprague Dawley rats were randomly divided into control, sham, ASCI, and MP-treated ASCI groups. After the induction of ASCI, we injected 30 mg/kg MP via the tail vein at various time points. The Tarlov scoring method was applied to evaluate neurological symptoms, and the wet-dry weights method was applied to measure the water content of the spinal cord. The motor function score of the ASCI group was significantly lower than that of the sham group, and the spinal water content was significantly increased. In addition, the levels of AQP4 and Kir4.1 were significantly increased, as was their degree of coexpression. Compared with that in the ASCI group, the motor function score and the water content were significantly increased in the MP group; in addition, the expression and coexpression of AQP4 and Kir4.1 were significantly reduced. Methylprednisolone inhibited medullospinal edema in rats with acute spinal cord injury, possibly by reducing the coexpression of aquaporin 4 and Kir4.1 in medullospinal tissues.

Activity-dependent plasticity in spinal cord injury

PubMed Central

Lynskey, James V.; Belanger, Adam; Jung, Ranu

2008-01-01

The adult mammalian central nervous system (CNS) is capable of considerable plasticity, both in health and disease. After spinal neurotrauma, the degrees and extent of neuroplasticity and recovery depend on multiple factors, including the level and extent of injury, postinjury medical and surgical care, and rehabilitative interventions. Rehabilitation strategies focus less on repairing lost connections and more on influencing CNS plasticity for regaining function. Current evidence indicates that strategies for rehabilitation, including passive exercise, active exercise with some voluntary control, and use of neuroprostheses, can enhance sensorimotor recovery after spinal cord injury (SCI) by promoting adaptive structural and functional plasticity while mitigating maladaptive changes at multiple levels of the neuraxis. In this review, we will discuss CNS plasticity that occurs both spontaneously after SCI and in response to rehabilitative therapies. PMID:18566941

Effect of Teriparatide, Vibration and the Combination on Bone Mass and Bone Architecture in Chronic Spinal Cord Injury

DTIC Science & Technology

2015-12-01

lateral condyles of the tibia and the anterioposterior axis was oriented orthogonally. The CT Hounsfield units were converted to calcium hydroxyapatite...orthogonally. The CT Hounsfield units were converted to calcium hydroxyapatite density rha using a linear relationship established with the phantom...concentration (QRM, Moehrendorf, Germany). The phantom allowed conversion of computed tomography Hounsfield units into hydroxyapatite equivalent density

Transcutaneous spinal direct current stimulation of the lumbar and sacral spinal cord: a modelling study

NASA Astrophysics Data System (ADS)

Fernandes, Sofia R.; Salvador, Ricardo; Wenger, Cornelia; de Carvalho, Mamede; Miranda, Pedro C.

2018-06-01

Objective. Our aim was to perform a computational study of the electric field (E-field) generated by transcutaneous spinal direct current stimulation (tsDCS) applied over the thoracic, lumbar and sacral spinal cord, in order to assess possible neuromodulatory effects on spinal cord circuitry related with lower limb functions. Approach. A realistic volume conductor model of the human body consisting of 14 tissues was obtained from available databases. Rubber pad electrodes with a metallic connector and a conductive gel layer were modelled. The finite element (FE) method was used to calculate the E-field when a current of 2.5 mA was passed between two electrodes. The main characteristics of the E-field distributions in the spinal grey matter (spinal-GM) and spinal white matter (spinal-WM) were compared for seven montages, with the anode placed either over T10, T8 or L2 spinous processes (s.p.), and the cathode placed over right deltoid (rD), umbilicus (U) and right iliac crest (rIC) areas or T8 s.p. Anisotropic conductivity of spinal-WM and of a group of dorsal muscles near the vertebral column was considered. Main results. The average E-field magnitude was predicted to be above 0.15 V m-1 in spinal cord regions located between the electrodes. L2-T8 and T8-rIC montages resulted in the highest E-field magnitudes in lumbar and sacral spinal segments (>0.30 V m-1). E-field longitudinal component is 3 to 6 times higher than the ventral-dorsal and right-left components in both the spinal-GM and WM. Anatomical features such as CSF narrowing due to vertebrae bony edges or disks intrusions in the spinal canal correlate with local maxima positions. Significance. Computational modelling studies can provide detailed information regarding the electric field in the spinal cord during tsDCS. They are important to guide the design of clinical tsDCS protocols that optimize stimulation of application-specific spinal targets.

Traumatic Brain and Spinal Cord Fatalities Among High School and College Football Players - United States, 2005-2014.

PubMed

Kucera, Kristen L; Yau, Rebecca K; Register-Mihalik, Johna; Marshall, Stephen W; Thomas, Leah C; Wolf, Susanne; Cantu, Robert C; Mueller, Frederick O; Guskiewicz, Kevin M

2017-01-06

An estimated 1.1 million high school and 75,000 college athletes participate in tackle football annually in the United States. Football is a collision sport; traumatic injuries are frequent (1,2), and can be fatal (3). This report updates the incidence and characteristics of deaths caused by traumatic brain injury and spinal cord injury (4) in high school and college football and presents illustrative case descriptions. Information was analyzed from the National Center for Catastrophic Sport Injury Research (NCCSIR). During 2005-2014, a total of 28 deaths (2.8 deaths per year) from traumatic brain and spinal cord injuries occurred among high school (24 deaths) and college football players (four deaths) combined. Most deaths occurred during competitions and resulted from tackling or being tackled. All four of the college deaths and 14 (58%) of the 24 high school deaths occurred during the last 5 years (2010-2014) of the 10-year study period. These findings support the need for continued surveillance and safety efforts (particularly during competition) to ensure proper tackling techniques, emergency planning for severe injuries, availability of medical care onsite during competitions, and assessment that it is safe to return to play following a concussion.

Attachment, hope, and participation: Testing an expanded model of Snyder's hope theory for prediction of participation for individuals with spinal cord injury.

PubMed

Blake, John; Yaghmaian, Rana; Brooks, Jessica; Fais, Connor; Chan, Fong

2018-05-01

The aim of the study was to test an expanded model of Snyder's hope theory for prediction of participation for individuals with spinal cord injury (SCI). Statistical model testing focused on evaluation of hope theory constructs (i.e., agency thoughts and pathways thoughts) as serial mediators of relationships between attachment and community participation. Quantitative, cross-sectional, descriptive design using multiple regression and correlational techniques. The sample comprised 108 persons with SCI recruited from spinal cord injury advocacy organizations in the United States, the United Kingdom, and Canada. Secure attachment, avoidant attachment, anxious attachment, and the hope constructs were significantly related to participation. Significant mediational effects were observed when agency thoughts and pathways thoughts were specified as mediators in series between attachment and community participation for people with SCI (i.e., agency specified as M1 and pathways specified as M2). Results provide support for Snyder's theoretical conceptualization and the use of hope-based interventions by rehabilitation practitioners for improving global participation outcomes for people with SCI who experience attachment-related difficulties. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

The recovery of 5-HT transporter and 5-HT immunoreactivity in injured rat spinal cord.

PubMed

Saruhashi, Yasuo; Matsusue, Yoshitaka; Fujimiya, Mineko

2009-09-01

Experimental spinal cord injury. To determine the role of serotonin (5-HT) and 5-HT transporter in recovery from spinal cord injury. We examined 5-HT and 5-HT transporter of spinal cord immunohistologically and assessed locomotor recovery after extradural compression at the thoracic (T8) spinal cord in 21 rats. Eighteen rats had laminectomy and spinal cord injury, while the remaining three rats received laminectomy only. All rats were evaluated every other day for 4 weeks, using a 0-14 point scale open field test. Extradural compression markedly reduced mean hindlimbs scores from 14 to 1.5 +/- 2.0 (mean +/- standard error of mean). The rats recovered apparently normal walking by 4 weeks. The animals were perfused with fixative 1-3 days, 1, 2 and 4 weeks (three rats in each) after a spinal cord injury. The 5-HT transporter immunohistological study revealed a marked reduction of 5-HT transporter-containing terminals by 1 day after injury. By 4 weeks after injury, 5-HT transporter immunoreactive terminals returned to the control level. The 5-HT immunohistological study revealed a reduction of 5-HT-containing terminals by 1 week after injury. By 4 weeks after injury, 5-HT immunoreactive fibers and terminals returned to the control level. We estimated the recovery of 5-HT transporter and 5-HT neural elements in lumbosacral ventral horn by ranking 5-HT transporter and 5-HT staining intensity and counting 5-HT and 5-HT transporter terminals. The return of 5-HT transporter and 5-HT immunoreactivity of the lumbosacral ventral horn correlated with locomotor recovery, while 5-HT transporter showed closer relationship with locomotor recovery than 5-HT. The presence of 5-HT transporter indicates that the 5-HT fibers certainly function. This study shows that return of the function of 5-HT fibers predict the time course and extent of locomotory recovery after thoracic spinal cord injury.

Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs.

PubMed

Lim, Ji Hey; Byeon, Ye Eun; Ryu, Hak Hyun; Jeong, Yun Hyeok; Lee, Young Won; Kim, Wan Hee; Kang, Kyung Sun; Kweon, Oh Kyeong

2007-09-01

This study was to determine the effects of allogenic umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) and recombinant methionyl human granulocyte colony-stimulating factor (rmhGCSF) on a canine spinal cord injury model after balloon compression at the first lumbar vertebra. Twenty-five adult mongrel dogs were assigned to five groups according to treatment after a spinal cord injury: no treatment (CN); saline treatment (CP); rmhGCSF treatment (G); UCB-MSCs treatment (UCB-MSC); co-treatment (UCBG). The UCBMSCs isolated from cord blood of canine fetuses were prepared as 10(6) cells/150 microl saline. The UCB-MSCs were directly injected into the injured site of the spinal cord and rmhGCSF was administered subcutaneously 1 week after the induction of spinal cord injury. The Olby score, magnetic resonance imaging, somatosensory evoked potentials and histopathological examinations were used to evaluate the functional recovery after transplantation. The Olby scores of all groups were zero at the 0-week evaluation. At 2 week after the transplantation, the Olby scores in the groups with the UCB-MSC and UCBG were significantly higher than in the CN and CP groups. However, there were no significant differences between the UCB-MSC and UCBG groups, and between the CN and CP groups. These comparisons remained stable at 4 and 8 week after transplantation. There was significant improvement in the nerve conduction velocity based on the somatosensory evoked potentials. In addition, a distinct structural consistency of the nerve cell bodies was noted in the lesion of the spinal cord of the UCB-MSC and UCBG groups. These results suggest that transplantation of the UCB-MSCs resulted in recovery of nerve function in dogs with a spinal cord injury and may be considered as a therapeutic modality for spinal cord injury.

Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs

PubMed Central

Lim, Ji-Hey; Byeon, Ye-Eun; Ryu, Hak-Hyun; Jeong, Yun-Hyeok; Lee, Young-Won; Kim, Wan Hee

2007-01-01

This study was to determine the effects of allogenic umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) and recombinant methionyl human granulocyte colony-stimulating factor (rmhGCSF) on a canine spinal cord injury model after balloon compression at the first lumbar vertebra. Twenty-five adult mongrel dogs were assigned to five groups according to treatment after a spinal cord injury: no treatment (CN); saline treatment (CP); rmhGCSF treatment (G); UCB-MSCs treatment (UCB-MSC); co-treatment (UCBG). The UCB-MSCs isolated from cord blood of canine fetuses were prepared as 106 cells/150 µl saline. The UCB-MSCs were directly injected into the injured site of the spinal cord and rmhGCSF was administered subcutaneously 1 week after the induction of spinal cord injury. The Olby score, magnetic resonance imaging, somatosensory evoked potentials and histopathological examinations were used to evaluate the functional recovery after transplantation. The Olby scores of all groups were zero at the 0-week evaluation. At 2 week after the transplantation, the Olby scores in the groups with the UCB-MSC and UCBG were significantly higher than in the CN and CP groups. However, there were no significant differences between the UCB-MSC and UCBG groups, and between the CN and CP groups. These comparisons remained stable at 4 and 8 week after transplantation. There was significant improvement in the nerve conduction velocity based on the somatosensory evoked potentials. In addition, a distinct structural consistency of the nerve cell bodies was noted in the lesion of the spinal cord of the UCB-MSC and UCBG groups. These results suggest that transplantation of the UCB-MSCs resulted in recovery of nerve function in dogs with a spinal cord injury and may be considered as a therapeutic modality for spinal cord injury. PMID:17679775