... and drive. Do not dive into pools, lakes, rivers, and other bodies of water, particularly if you cannot determine the depth of the ... Central nervous system Spinal cord injury Spinal anatomy Two person roll - ...
... Types of illnesses and disabilities Spinal cord injury Spinal cord injury Read advice from Dr. Jeffrey Rabin , a ... your health on a daily basis. Living with spinal cord injury — your questions answered top What are pediatric ...
... Counseling About Blog Facing Disability Jeff Shannon Donate Spinal Cord Injury Map Loss of function depends on what ... control. Learn more about spinal cord injuries. A spinal cord injury affects the entire family FacingDisability is designed ...
Resources - spinal injury ... The following organizations are good resources for information on spinal injury : National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/Disorders/All-Disorders/Spinal-Cord- ...
... care for people with spinal cord injuries and aggressive treatment and rehabilitation can minimize damage to the ... care for people with spinal cord injuries and aggressive treatment and rehabilitation can minimize damage to the ...
... your body and your brain. A spinal cord injury disrupts the signals. Spinal cord injuries usually begin with a blow that fractures or ... bone disks that make up your spine. Most injuries don't cut through your spinal cord. Instead, ...
West, Bethany A; Naumann, Rebecca B
A previous analysis of National Vital Statistics System data for 2003-2007 that examined disparities in rates of motor vehicle-related death by race/ethnicity and sex found that death rates for American Indians/Alaska Natives were two to four times the rates of other races/ethnicities. To address the disparity in motor vehicle-related injuries and deaths among American Indians/Alaska Natives, CDC funded four American Indian tribes during 2004-2009 to tailor, implement, and evaluate evidence-based road safety interventions. During the implementation of these four motor vehicle-related injury prevention pilot programs, seat belt and child safety seat use increased and alcohol-impaired driving decreased. Four American Indian/Alaska Native tribal communities-the Tohono O'odham Nation, the Ho-Chunk Nation, the White Mountain Apache Tribe, and the San Carlos Apache Tribe-implemented evidence-based road safety interventions to reduce motor vehicle-related injuries and deaths. Each community selected interventions from the Guide to Community Preventive Services and implemented them during 2004-2009. Furthermore, each community took a multifaceted approach by incorporating several strategies, such as school and community education programs, media campaigns, and collaborations with law enforcement officers into their programs. Police data and direct observational surveys were the main data sources used to assess results of the programs. Results included increased use of seat belts and child safety seats, increased enforcement of alcohol-impaired driving laws, and decreased motor vehicle crashes involving injuries or deaths. CDC's Office of Minority Health and Health Equity selected the intervention analysis and discussion as an example of a program that might be effective for reducing motor vehicle-related injury disparities in the United States. The Guide to Community Preventive Services recognizes these selected interventions as effective; this report examines the
... is "Braingate" research? What is the status of stem-cell research? How would stem-cell therapies work in the treatment of spinal cord injuries? What does stem-cell research on animals tell us? When can we ...
... to send and receive messages to and from the brain. About 200,000 people in the United States have spinal cord injuries. Most injuries occur from a traumatic event, according to the National Spinal Cord Injury ...
About 5% of spinal injuries occur in children – however the consequences to the society are devastating, all the more so because the cervical spine is more commonly affected. Anatomical differences with adults along with the inherent elasticity of the pediatric spine, makes these injuries a biomechanically separate entity. Hence clinical manifestations are unique, one of which is the Spinal Cord Injury Without Radiological Abnormality. With the advent of high quality MRI and CT scan along with digital X-ray, it is now possible to exactly delineate the anatomical location, geometrical configuration, and the pathological extent of the injury. This has improved the management strategies of these unfortunate children and the role of surgical stabilization in unstable injuries can be more sharply defined. However these patients should be followed up diligently because of the recognized long term complications of spinal deformity and syringomyelia. PMID:22855681
(1).—Varieties of spinal injuries, the three groups of common usage: fractures, dislocations, fracture-dislocations. Shall not refer in detail to fractures of the spinous or transverse processes. (2) Mechanics of injury to vertebræ. Two variables: (1) the nature of the bones; (2) the qualities of the force. Spinal injury usually caused by indirect violence. (3) The different results of injuries applied to the head; may break skull, failing that, the neck. Atlas fracture. Difference in qualities of the force causing atlas fracture and low cervical dislocation. (4) The compound nature of the vertebral body. The two columns, anterior, spongy; posterior, compact. The nature of wedge-compression of the vertebral body. Variations in the shape of the wedge. Reasons. Occur at all levels, including cervical spine. (5) Frequency of injury at different levels of vertebral column. “Localization” of injury. The two places of the graph of injury. The cervical at C. 5. Reason. The thoracic-lumbar peak at T. 12, L. 1 industrial. Is there a third peak at C. 2? (6) The effects of violent flexion of the spine: cervical flexion causes luxation at C. 5 or so. Extension causes fracture of odontoid. Violent flexion and extension therefore cause injury at very different levels. Thoracic region, why is there no “peak” of injury at T.6, 7? Lumbar region. (7) Displacement of fragments. Continuation of violence after the essential injury has been effected. Kümmell's disease, no inflammatory process involved. (8) Injury to the intervertebral discs, essential for displacement. Imperfect rupture a cause for difficulty in reducing luxations. The worst cases those in which it is most easily done, but most of these have cord damage. (9) Spinal injury from minimal violence. Examples of trivial cases, diving, brushing hair and so forth. Vertebral displacement in disease a much more serious thing. (10) Curious stability of many cervical luxations. Reasons. Locking of the inferior
Conway, Cassandra Sligh D.; Gooden, Randy; Nowell, Jennifer; Wilson, Navodda
This paper will shed light on the lives of persons with spinal cord injuries by revealing the literature on spinal cord injuries that focuses on research that can shed light on attitudes towards persons with spinal cord injuries. The background literature related to incidences, the definition of spinal cord injury, and vocational opportunities are…
Blum, Jeremy J; Scullion, Paul; Morgan, Richard M; Digges, Kennerly; Kan, Cing-Dao; Park, Shinhee; Bae, Hanil
This study specifically investigated a range of vehicle-related factors that are associated with a lower risk of serious or fatal injury to a belted driver in a head-on collision. This analysis investigated a range of structural characteristics, quantities that describes the physical features of a passenger vehicle, e.g., stiffness or frontal geometry. The study used a data-mining approach (classification tree algorithm) to find the most significant relationships between injury outcome and the structural variables. The algorithm was applied to 120,000 real-world, head-on collisions, from the National Highway Traffic Safety Administration's (NHTSA's) State Crash data files, that were linked to structural attributes derived from frontal crash tests performed as part of the USA New Car Assessment Program. As with previous literature, the analysis found that the heavier vehicles were correlated with lower injury risk to their drivers. This analysis also found a new and significant correlation between the vehicle's stiffness and injury risk. When an airbag deployed, the vehicle's stiffness has the most statistically significant correlation with injury risk. These results suggest that in severe collisions, lower intrusion in the occupant cabin associated with higher stiffness is at least as important to occupant protection as vehicle weight for self-protection of the occupant. Consequently, the safety community might better improve self-protection by a renewed focus on increasing vehicle stiffness in order to improve crashworthiness in head-on collisions.
... colleagues, with an educational grant from Pfizer Inc. University of Washington-operated SCI Clinics: Harborview Medical Center ... Spinal Cord Injury Clinic nurses: 206-744-5862 University of Washington Medical Center Rehabilitation Medicine Clinic 1959 ...
Background/Objective: In the course of examining spinal motor function in many hundreds of people with traumatic spinal cord injury, we encountered 6 individuals who developed involuntary and rhythmic contractions in muscles of their legs. Although there are many reports of unusual muscle activation patterns associated with different forms of myoclonus, we believe that certain aspects of the patterns seen with these 6 subjects have not been previously reported. These patterns share many features with those associated with a spinal central pattern generator for walking. Methods: Subjects in this case series had a history of chronic injury to the cervical spinal cord, resulting in either complete (ASIA A; n = 4) or incomplete (ASIA D; n = 2) quadriplegia. We used multi-channel electromyography recordings of trunk and leg muscles of each subject to document muscle activation patterns associated with different postures and as influenced by a variety of sensory stimuli. Results: Involuntary contractions spanned multiple leg muscles bilaterally, sometimes including weak abdominal contractions. Contractions were smooth and graded and were highly reproducible in rate for a given subject (contraction rates were 0.3–0.5 Hz). These movements did not resemble the brief rapid contractions (ie, "jerks") ascribed to some forms of spinal myoclonus. For all subjects, the onset of involuntary muscle contraction was dependent upon hip angle; contractions did not occur unless the hips (and knees) were extended (ie, subjects were supine). In the 4 ASIA A subjects, contractions occurred simultaneously in all muscles (agonists and antagonists) bilaterally. In sharp contrast, contractions in the 2 ASIA D subjects were reciprocal between agonists and antagonists within a limb and alternated between limbs, such that movements in these 2 subjects looked just like repetitive stepping. Finally, each of the 6 subjects had a distinct pathology of their spinal cord, nerve roots, distal trunk
Zhang, Ning; Fang, Marong; Chen, Haohao; Gou, Fangming; Ding, Mingxing
Because there is no curative treatment for spinal cord injury, establishing an ideal animal model is important to identify injury mechanisms and develop therapies for individuals suffering from spinal cord injuries. In this article, we systematically review and analyze various kinds of animal models of spinal cord injury and assess their advantages and disadvantages for further studies. PMID:25598784
... spinal cord injury? Where is the nearest SCI Model System of Care? Emergency Medical Services Hospital (Acute) Care Rehabilitation More ... spinal cord injury? Where is the nearest SCI Model System of Care? Follow Us! Get Email Updates Questions & Comments Suggest ...
Zulkipli, Zarir Hafiz; Abdul Rahmat, Abdul Manap; Mohd Faudzi, Siti Atiqah; Paiman, Noor Faradila; Wong, Shaw Voon; Hassan, Ahamedali
This study presents an analysis of crash characteristics of motorcyclists who sustained spinal injuries in motorcycle crashes. The aim of the study is to identify the salient crash characteristics that would help explain spinal injury risks for motorcyclists. Data were retrospectively collected from police case reports that were archived at MIROS from year 2005 to 2007. The data were categorized into two subcategories; the first group was motorcycle crashes with spinal injury (case) and the second group was motorcycle crashes without spinal injury (control). A total of 363 motorcyclists with spinal injury and 873 motorcyclists without spinal injury were identified and analyzed. Descriptive analysis and multivariate analysis were performed in order to determine the odds of each characteristic in contributing to spinal injury. Single vehicle crash, collision with fixed objects and crash configuration were found to have significant influence on motorcyclists in sustaining spinal injury (p<0.05). Although relatively few than other impact configurations, the rear-end impacted motorcyclist shows the highest risk of spinal injury. Helmets have helped to reduce head injury but they did not seem to offer corresponding protection for the spine in the study. With a growing number of young motorcyclists, further efforts are needed to find effective measures to help reduce the crash incidents and severity of spinal injury. In sum, the study provides some insights on some vital crash characteristics associated with spinal injury that can be further investigated to determine the appropriate counter-measures and prevention strategies to reduce spinal injury.
Piazza, Matthew; Schuster, James
Although timing for surgical intervention after spinal cord injury remains controversial, there is accumulating evidence suggesting that early surgery may improve neurologic outcomes, particularly with incomplete spinal cord injury, and may reduce non-neurologic complications and health care resource utilization. Moreover, even in patients with complete spinal cord injury, minor improvement in neurologic function can lead to significant changes in quality of life. This article reviews the experimental and clinical data examining surgical timing after spinal cord injury.
Ullrich, Philip M
Pain is one of the most common, severe, and treatment-resistant complications that follows SCI. Recent years have seen a surge of research on methods for assessing and treating spinal cord injury pain. In this article, pain after SCI is reviewed in terms of nature, scope, assessment techniques, and treatment strategies.
Nas, Kemal; Yazmalar, Levent; Şah, Volkan; Aydın, Abdulkadir; Öneş, Kadriye
Spinal cord injury (SCI) is the injury of the spinal cord from the foramen magnum to the cauda equina which occurs as a result of compulsion, incision or contusion. The most common causes of SCI in the world are traffic accidents, gunshot injuries, knife injuries, falls and sports injuries. There is a strong relationship between functional status and whether the injury is complete or not complete, as well as the level of the injury. The results of SCI bring not only damage to independence and physical function, but also include many complications from the injury. Neurogenic bladder and bowel, urinary tract infections, pressure ulcers, orthostatic hypotension, fractures, deep vein thrombosis, spasticity, autonomic dysreflexia, pulmonary and cardiovascular problems, and depressive disorders are frequent complications after SCI. SCI leads to serious disability in the patient resulting in the loss of work, which brings psychosocial and economic problems. The treatment and rehabilitation period is long, expensive and exhausting in SCI. Whether complete or incomplete, SCI rehabilitation is a long process that requires patience and motivation of the patient and relatives. Early rehabilitation is important to prevent joint contractures and the loss of muscle strength, conservation of bone density, and to ensure normal functioning of the respiratory and digestive system. An interdisciplinary approach is essential in rehabilitation in SCI, as in the other types of rehabilitation. The team is led by a physiatrist and consists of the patients’ family, physiotherapist, occupational therapist, dietician, psychologist, speech therapist, social worker and other consultant specialists as necessary. PMID:25621206
Nas, Kemal; Yazmalar, Levent; Şah, Volkan; Aydın, Abdulkadir; Öneş, Kadriye
Spinal cord injury (SCI) is the injury of the spinal cord from the foramen magnum to the cauda equina which occurs as a result of compulsion, incision or contusion. The most common causes of SCI in the world are traffic accidents, gunshot injuries, knife injuries, falls and sports injuries. There is a strong relationship between functional status and whether the injury is complete or not complete, as well as the level of the injury. The results of SCI bring not only damage to independence and physical function, but also include many complications from the injury. Neurogenic bladder and bowel, urinary tract infections, pressure ulcers, orthostatic hypotension, fractures, deep vein thrombosis, spasticity, autonomic dysreflexia, pulmonary and cardiovascular problems, and depressive disorders are frequent complications after SCI. SCI leads to serious disability in the patient resulting in the loss of work, which brings psychosocial and economic problems. The treatment and rehabilitation period is long, expensive and exhausting in SCI. Whether complete or incomplete, SCI rehabilitation is a long process that requires patience and motivation of the patient and relatives. Early rehabilitation is important to prevent joint contractures and the loss of muscle strength, conservation of bone density, and to ensure normal functioning of the respiratory and digestive system. An interdisciplinary approach is essential in rehabilitation in SCI, as in the other types of rehabilitation. The team is led by a physiatrist and consists of the patients' family, physiotherapist, occupational therapist, dietician, psychologist, speech therapist, social worker and other consultant specialists as necessary.
Cook, Daniel W.
Reviewing literature on the psychological impact of spinal cord injury suggests: (a) depression may not be a precondition for injury adjustment; (b) many persons sustaining cord injury may have experienced psychological disruption prior to injury; and (c) indexes of rehabilitation success need to be developed for the spinal cord injured. (Author)
Brand, M Colleen
Neonatal spinal cord injury can occur in utero, as well as after either a difficult delivery or a nontraumatic delivery. Spinal cord injury can also be related to invasive nursery procedures or underlying neonatal pathology. Early clinical signs of spinal cord injury that has occurred in utero or at delivery includes severe respiratory compromise and profound hypotonia. Knowledge of risk factors and awareness of symptoms is required for early recognition and appropriate treatment. This article reviews the embryological development of the spinal column highlighting mechanisms of injury and identifying underlying factors that increase the risk of spinal cord injury in newborns. Signs and symptoms of injury, cervical spine immobilization, and the differential diagnosis are discussed. Nursing implications, general prognosis, and research in spinal cord injury are provided.
Jones, Zachary B; Ren, Yi
Spinal cord injury (SCI) is a debilitating condition that affects millions of individuals worldwide. Despite progress over the last few decades, the molecular mechanisms of secondary SCI that continue to occur days and weeks after the original trauma remain poorly understood. As a result, current therapies for SCI are only marginally effective. Sphingolipids, a diverse class of bioactive lipids, have been shown to regulate SCI repair and key secondary injury processes such as apoptosis, ischemia and inflammation. This review will discuss the numerous roles of sphingolipids and highlight the potential of sphingolipid-targeted therapies for SCI. PMID:27570580
Apple, D F; Anson, C A; Hunter, J D; Bell, R B
To identify special characteristics of the pediatric spinal cord-injured (SCI) population, we analyzed a database of 1,770 traumatic SCI patients; 88 (5%) fell into the two pediatric subgroups: 0-12 years (n = 26) and 13-15 years (n = 62) at time of injury. Differences between age groups were identified with regard to demographics, neurologic characteristics, associated injuries and complications, and management. Mode level of bony injury was C2 in preteens, C4 in teens, and C4-C5 in adults. Scoliosis developed far more frequently in children, particularly preteens (23%), than in adults (5%). Violent etiologies, predominantly gunshots, accounted for a disproportionate share of injuries to preteens (19%) and African-Americans (28%), as compared with adults (12%) and Caucasians (7%). This last finding underscores the urgent need to mount a response to the nationwide proliferation of gunshot-related SCI in children and minorities.
Cristante, Alexandre Fogaça; de Barros Filho, Tarcísio Eloy Pessoa; Marcon, Raphael Martus; Letaif, Olavo Biraghi; da Rocha, Ivan Dias
This study reviews the literature concerning possible therapeutic approaches for spinal cord injury. Spinal cord injury is a disabling and irreversible condition that has high economic and social costs. There are both primary and secondary mechanisms of damage to the spinal cord. The primary lesion is the mechanical injury itself. The secondary lesion results from one or more biochemical and cellular processes that are triggered by the primary lesion. The frustration of health professionals in treating a severe spinal cord injury was described in 1700 BC in an Egyptian surgical papyrus that was translated by Edwin Smith; the papyrus reported spinal fractures as a “disease that should not be treated.” Over the last two decades, several studies have been performed to obtain more effective treatments for spinal cord injury. Most of these studies approach a patient with acute spinal cord injury in one of four manners: corrective surgery or a physical, biological or pharmacological treatment method. Science is unraveling the mechanisms of cell protection and neuroregeneration, but clinically, we only provide supportive care for patients with spinal cord injuries. By combining these treatments, researchers attempt to enhance the functional recovery of patients with spinal cord injuries. Advances in the last decade have allowed us to encourage the development of experimental studies in the field of spinal cord regeneration. The combination of several therapeutic strategies should, at minimum, allow for partial functional recoveries for these patients, which could improve their quality of life. PMID:23070351
Spinal Cord Injury; Spinal Cord Injuries; Trauma, Nervous System; Wounds and Injuries; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Gonadal Disorders; Endocrine System Diseases; Hypogonadism; Genital Diseases, Male
Piontkowski, Stephen R; Peabody, Jon S; Reede, Christine; Velascosoltero, José; Tsatoke, Gordon; Shelhamer, Timothy; Hicks, Kenny R
Unintentional injury is a significant public health burden for American Indians and Alaska Natives and was the leading cause of death among those aged 1 to 44 years between 1999 and 2004. Of those deaths, motor vehicle-related deaths cause the most mortality, justifying the need for intervention at an American Indian Reservation in Arizona (United States). We describe motor vehicle injury prevention program operations from 2004 through 2013. This community-based approach led by a multidisciplinary team primarily comprised of environmental public health and law enforcement personnel implemented evidence-based strategies to reduce the impact of motor vehicle-related injuries and deaths, focusing on reducing impaired driving and increasing occupant restraint use. Strategies included: mass media campaigns to enhance awareness and outreach; high-visibility sobriety checkpoints; passing and enforcing 0.08% blood alcohol concentration limits for drivers and primary occupant restraint laws; and child car seat distribution and education. Routine monitoring and evaluation data showed a significant 5% to 7% annual reduction of motor vehicle crashes (MVCs), nighttime MVCs, MVCs with injuries/fatalities, and nighttime MVCs with injuries/fatalities between 2004 and 2013, but the annual percent change in arrests for driving under the influence (DUI) was not significant. There was also a 144% increase in driver/front seat passenger seat belt use, from 19% in 2011 before the primary occupant restraint law was enacted to 47% during the first full year of enforcement (2013). Car seat checkpoint data also suggested a 160% increase in car seat use, from less than 20% to 52% in 2013. Implementation of evidence-based strategies in injury prevention, along with employment of key program approaches such as strong partnership building, community engagement, and consistent staffing and funding, can narrow the public health disparity gap experienced among American Indian and Alaska Native
Yarkony, G M; Novick, A K; Roth, E J; Kirschner, K L; Rayner, S; Betts, H B
Galactorrhea, a secretion of milk or milk-like products from the breast in the absence of parturition, has been reported to occur in women with spinal cord injuries in association with amenorrhea and hyperprolactinemia. Four cases of galactorrhea in association with spinal cord injury are reported. Galactorrhea developed in four spinal cord injured women who had thoracic paraplegia. The onset of galactorrhea was from one month to five months after injury. Although the onset of galactorrhea may have been related to prescribed medications in all four cases, insufficient data exist to draw conclusions. The three women whose galactorrhea persisted declined treatment and galactorrhea continuing for more than two years in one instance. We conclude that galactorrhea with or without amenorrhea may develop after a spinal cord injury and that spinal cord injured women may have an enhanced sensitivity to medication-induced galactorrhea.
Background: Knowledge of the causes of spinal cord injury (SCI) and associated factors is critical in the development of successful prevention programs. Objective: This study analyzed data from the National SCI Database (NSCID) and National Shriners SCI Database (NSSCID) in the United States to examine specific etiologies of SCI by age, sex, race, ethnicity, day and month of injury, and neurologic outcomes. Methods: NSCID and NSSCID participants who had a traumatic SCI from 2005 to 2011 with known etiology were included in the analyses (N=7,834). Thirty-seven causes of injury documented in the databases were stratified by personal characteristics using descriptive analysis. Results: The most common causes of SCI were automobile crashes (31.5%) and falls (25.3%), followed by gunshot wounds (10.4%), motorcycle crashes (6.8%), diving incidents (4.7%), and medical/surgical complications (4.3%), which collectively accounted for 83.1% of total SCIs since 2005. Automobile crashes were the leading cause of SCI until age 45 years, whereas falls were the leading cause after age 45 years. Gunshot wounds, motorcycle crashes, and diving caused more SCIs in males than females. The major difference among race/ethnicity was in the proportion of gunshot wounds. More SCIs occurred during the weekends and warmer months, which seemed to parallel the increase of motorcycle- and diving-related SCIs. Level and completeness of injury are also associated with etiology of injury. Conclusions: The present findings suggest that prevention strategies should be tailored to the targeted population and major causes to have a meaningful impact on reducing the incidence of SCI. PMID:23678280
Mackie, J. William; McCormack, Rebecca; Campbell, Duncan
Activity for many disabled persons often begins as therapy, but the additional rewards derived from exercise must be appreciated. Public attitudes toward disabled persons have changed during the last few decades, recently focusing on abilities rather than on disabilities. The family physician of patients with spinal cord injuries will assist in managing acute medical problems and the association with loss of some degree of physical capacity. Physicians also can guide these individuals to choose a life that remains active and interesting over a “house-bound,” but safe, existence. Sensitivity and timing play key roles in establishing exercise as an intergral part of a disabled individuals' altered lifestyle. The physician can advocate increased access to wheelchairs and other facilities that make life easier for disabled individuals. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:21248871
This conference proceeding summarizes current knowledge about the nutritional status and needs of the spinal cord injured patient. Topics covered include the aspects of spinal cord injury that influence nutrient intakes and status, and the nutrients most likely to be problematic in this diverse gro...
... the standard ASIA (American Spinal Injury Association) Impairment Scale for this diagnosis. X-rays, MRIs, or more ... entire length of the spine. The ASIA Impairment Scale has five classification levels, ranging from complete loss ...
Saadoun, Samira; Werndle, Melissa C; Lopez de Heredia, Luis; Papadopoulos, Marios C
MR scans from 65 patients with traumatic spinal cord injury were analysed; on admission 95% had evidence of cord compression - in 26% due to the dura, and in the remaining 74% due to extradural factors. Compression due to dural factors resolved with a half-life of 5.5 days. These findings suggest that bony decompression alone may not relieve spinal cord compression in the quarter of patients in whom dural factors are significant.
Engel, S.; Murphy, G. S.; Athanasou, J. A.; Hickey, L.
A study of 83 Australian adults with spinal cord injuries found that at least 56% had worked at some time post-injury and those who were working when surveyed had done so for an average of close to 10 years. Clerical, office, and administrative occupations proved to be the most suitable. (Author/CR)
Crane, Deborah A; Jaffee, Kenneth M; Kundu, Anjana
Background: This report describes a young woman with incomplete traumatic cervical spinal cord injury and intractable pruritus involving her dorsal forearm. Method: Case report. Findings: Anatomic distribution of the pruritus corresponded to the dermatomal distribution of her level of spinal cord injury and vertebral fusion. Symptoms were attributed to the spinal cord injury and possible cervical root injury. Pruritus was refractory to all treatments, including topical lidocaine, gabapentin, transcutaneous electrical nerve stimulation, intravenous Bier block, stellate ganglion block, and acupuncture. Conclusions: Further understanding of neuropathic pruritus is needed. Diagnostic workup of intractable pruritus should include advanced imaging to detect ongoing nerve root compression. If diagnostic studies suggest radiculopathy, epidural steroid injection should be considered. Because the autonomic nervous system may be involved in complex chronic pain or pruritic syndromes, sympatholysis via such techniques as stellate ganglion block might be effective. PMID:19777867
Spinal trauma can originate from internal or external sources. Injuries to the spinal cord can be classified as either concussive or compressive and concussive. The pathophysiologic events surrounding spinal cord injury include the primary injury (compression, concussion) and numerous secondary injury mechanisms (vascular, biochemical, electrolyte), which are mediated by excessive oxygen free radicles, neurotransmitter and electrolyte alterations in cell membrane permeability, excitotoxic amino acids, and various other biochemical factors that collectively result in reduced SCBF, ischemia, and eventual necrosis of the gray and white matter. Management of acute spinal cord injuries includes the use of a high-dose corticosteroid regimen within the initial 8 hours after trauma. Sodium prednisolone and methylprednisolone, at recommended doses, act as oxygen radical scavengers and are anti-inflammatory. Additional considerations are the stability of the vertebral column, other conditions associated with trauma (i.e., pneumothorax), and the presence or absence of spinal cord compression, which may warrant surgical therapy. Vertebral fractures or luxations can occur in any area of the spine but most commonly occur at the junction of mobile and immobile segments. Dorsal and dorsolateral surgical approaches are applicable to the lumbosacral and thoracolumbar spine and dorsal and ventral approaches to the cervical spine. Indications for surgical intervention include spinal cord compression and vertebral instability. Instability can be determined from the type of fracture, how many of the three compartments of the vertebrae are disrupted, and on occasion, by carefully positioned stress studies of fluoroscopy. Decompression (dorsal laminectomy, hemilaminectomy, or ventral cervical slot) is employed when compression of the spinal cord exists. The hemilaminectomy (unilateral or bilateral) causes less instability than dorsal laminectomy and therefore should be used when practical
Nardone, Raffaele; Höller, Yvonne; Thomschewski, Aljoscha; Höller, Peter; Lochner, Piergiorgio; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen
Changes in descending serotonergic innervation of spinal neural activity have been implicated in symptoms of paralysis, spasticity, sensory disturbances and pain following spinal cord injury (SCI). Serotonergic neurons possess an enhanced ability to regenerate or sprout after many types of injury, including SCI. Current research suggests that serotonine (5-HT) release within the ventral horn of the spinal cord plays a critical role in motor function, and activation of 5-HT receptors mediates locomotor control. 5-HT originating from the brain stem inhibits sensory afferent transmission and associated spinal reflexes; by abolishing 5-HT innervation SCI leads to a disinhibition of sensory transmission. 5-HT denervation supersensitivity is one of the key mechanisms underlying the increased motoneuron excitability that occurs after SCI, and this hyperexcitability has been demonstrated to underlie the pathogenesis of spasticity after SCI. Moreover, emerging evidence implicates serotonergic descending facilitatory pathways from the brainstem to the spinal cord in the maintenance of pathologic pain. There are functional relevant connections between the descending serotonergic system from the rostral ventromedial medulla in the brainstem, the 5-HT receptors in the spinal dorsal horn, and the descending pain facilitation after tissue and nerve injury. This narrative review focussed on the most important studies that have investigated the above-mentioned effects of impaired 5-HT-transmission in humans after SCI. We also briefly discussed the promising therapeutical approaches with serotonergic drugs, monoclonal antibodies and intraspinal cell transplantation.
AWARD NUMBER: W81XWH-12-1-0587 TITLE: Directing Spinal Cord Plasticity: The Impact of Stretch ...Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on Functional Recovery after Spinal Cord Injury. 5b. GRANT NUMBER W81XWH-12-1...ABSTRACT Essentially all spinal cord injured patients receive stretching therapies beginning within the first few weeks post-injury. Despite
Examines effects of spinal cord injury on sexuality. Discusses areas of sexual concern. Provides suggestions for treating clients with spinal cord injuries experiencing sexual difficulties. Concludes that major goal in working with clients with spinal cord injuries who have sexual difficulties should be the facilitation of a creative and…
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).
Wang, Fangyong; Zhang, Junwei; Tang, Hehu; Li, Xiang; Jiang, Shudong; Lv, Zhen; Liu, Shujia; Chen, Shizheng; Liu, Jiesheng; Hong, Yi
[Purpose] The objective of the study was to compare the incidence, diagnosis, treatment, and prognosis of patients with spinal cord stab injury to those with the more common spinal cord contusion injury. [Subjects] Of patients hospitalized in China Rehabilitation Research Center from 1994 to 2014, 40 of those having a spinal cord stab injury and 50 with spinal cord contusion were selected. [Methods] The data of all patients were analyzed retrospectively. The cases were evaluated by collecting admission and discharge ASIA (American Spinal Injury Association) and ADL (activity of daily living) scores. [Results] After a comprehensive rehabilitation program, ASIA and ADL scores of patients having both spinal cord stab injury and spinal cord contusion significantly increase. However, the increases were noted to be higher in patients having a spinal cord stab injury than those having spinal cord contusion. [Conclusion] Comprehensive rehabilitation is effective both for patients having spinal cord stab injury and those with spinal cord contusion injury. However, the prognosis of patients having spinal cord stab injury is better than that of patients with spinal cord contusion.
Dowler, Denetta; Batiste, Linda; Whidden, Eddie
Examination of over 1,000 calls to the Job Accommodation Network involving workers with spinal cord injury identified the nature of the industry, job, career progression, and accessibility solutions. The number of calls increased dramatically after passage of the Americans with Disabilities Act. (SK)
Sandu, AM; Popescu, M; Iacobini, MA; Stoian, R; Neascu, C; Popa, F
The aim of this article is to analyze cardiac dysfunctions occurring after spinal cord injury (SCI). Cardiac dysfunctions are common complications following SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. We reviewed epidemiology of cardiac disturbances after SCI, and neuroanatomy and pathophysiology of autonomic nervous system, sympathetic and parasympathetic. SCI causes disruption of descendent pathways from central control centers to spinal sympathetic neurons, originating into intermediolateral nuclei of T1–L2 spinal cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant cardiac dysfunction. Impairment of autonomic nervous control system, mostly in patients with cervical or high thoracic SCI, causes cardiac dysrrhythmias, especially bradycardia and, rarely, cardiac arrest, or tachyarrhytmias and hypotension. Specific complication dependent on the period of time after trauma like spinal shock and autonomic dysreflexia are also reviewed. Spinal shock occurs during the acute phase following SCI and is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe bradycardia and hypotension. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Besides all this, additional cardiac complications, such as cardiac deconditioning and coronary heart disease may also occur. Proper prophylaxis, including nonpharmacologic and pharmacological strategies and cardiac rehabilitation diminish occurrence of the cardiac dysfunction following
Elective colostomy is an accepted method of bowel management for patients who have had a spinal cord injury (SCI). Approximately 2.4% of patients with SCI have a colostomy, and traditionally it is performed as a last resort several years after injury, and only if bowel complications persist when all other methods have failed. This is despite evidence that patients find a colostomy easier to manage and frequently report wishing it had been performed earlier. It was noticed in the author's spinal unit that increasing numbers of patients were requesting colostomy formation during inpatient rehabilitation following SCI. No supporting literature was found for this; it appears to be an emerging and untested practice. This article explores colostomy formation as a method of bowel management in patients with SCI, considers the optimal time for colostomy formation after injury and examines issues for health professionals.
Popa, F; Grigorean, VT; Onose, G; Sandu, AM; Popescu, M; Burnei, G; Strambu, V; Sinescu, C
The aim of this article is to analyze the vascular dysfunctions occurring after spinal cord injury (SCI). Vascular dysfunctions are common complications of SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. Neuroanatomy and physiology of autonomic nervous system, sympathetic and parasympathetic, is reviewed. SCI implies disruption of descendent pathways from central centers to spinal sympathetic neurons, originating in intermediolateral nuclei of T1–L2 cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant vascular dysfunction. Spinal shock occurs during the acute phase following SCI and it is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe arterial hypotension and bradycardia. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Arterial hypotension with orthostatic hypotension occurs in both acute and chronic phases. The etiology is multifactorial. We described a few factors influencing the orthostatic hypotension occurrence in SCI: sympathetic nervous system dysfunction, low plasma catecholamine levels, rennin–angiotensin–aldosterone activity, peripheral alpha–adrenoceptor hyperresponsiveness, impaired function of baroreceptors, hyponatremia and low plasmatic volume, cardiovascular deconditioning, morphologic changes in sympathetic neurons, plasticity within spinal circuits, and motor deficit leading to loss of skeletal muscle pumping activity. Additional associated cardiovascular concerns in SCI, such as
Chari, Aswin; Hentall, Ian D.; Papadopoulos, Marios C.; Pereira, Erlick A. C.
Traumatic spinal cord injury (SCI) is a devastating neurological condition characterized by a constellation of symptoms including paralysis, paraesthesia, pain, cardiovascular, bladder, bowel and sexual dysfunction. Current treatment for SCI involves acute resuscitation, aggressive rehabilitation and symptomatic treatment for complications. Despite the progress in scientific understanding, regenerative therapies are lacking. In this review, we outline the current state and future potential of invasive and non-invasive neuromodulation strategies including deep brain stimulation (DBS), spinal cord stimulation (SCS), motor cortex stimulation (MCS), transcutaneous direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) in the context of SCI. We consider the ability of these therapies to address pain, sensorimotor symptoms and autonomic dysregulation associated with SCI. In addition to the potential to make important contributions to SCI treatment, neuromodulation has the added ability to contribute to our understanding of spinal cord neurobiology and the pathophysiology of SCI. PMID:28208601
As the biomedical engineering field expands, combination technologies are demonstrating enormous potential for treating human disease. In particular, intersections between the rapidly developing fields of gene therapy and tissue engineering hold promise to achieve tissue regeneration. Nonviral gene therapy uses plasmid DNA to deliver therapeutic proteins in vivo for extended periods of time. Tissue engineering employs biomedical materials, such as polymers, to support the regrowth of injured tissue. In this thesis, a combination strategy to deliver genes and drugs in a polymeric scaffold was applied to a spinal cord injury model. In order to develop a platform technology to treat spinal cord injury, several nonviral gene delivery systems and polymeric scaffolds were evaluated in vitro and in vivo. Nonviral vector trafficking was evaluated in primary neuronal culture to develop an understanding of the barriers to gene transfer in neurons and their supporting glia. Although the most efficient gene carrier in vitro differed from the optimal gene carrier in vivo, confocal and electron microscopy of these nonviral vectors provided insights into the interaction of these vectors with the nucleus. A novel pathway for delivering nanoparticles into the nuclei of neurons and Schwann cells via vesicle trafficking was observed in this study. Reporter gene expression levels were evaluated after direct and remote delivery to the spinal cord, and the optimal nonviral vector, dose, and delivery strategy were applied to deliver the gene encoding the basic fibroblast growth factor (bFGF) to the spinal cord. An injectable and biocompatible gel, composed of the amphiphillic polymer poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) was evaluated as a drug and gene delivery system in vitro, and combined with the optimized nonviral gene delivery system to treat spinal cord injury. Plasmid DNA encoding the bFGF gene and the therapeutic NEP1--40 peptide
Silver, J R
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.
Kramer, John L K; Geisler, Fred; Ramer, Leanne; Plunet, Ward; Cragg, Jacquelyn J
Recovery from acute spinal cord injury (SCI) is characterized by extensive heterogeneity, resulting in uncertain prognosis. Reliable prediction of recovery in the acute phase benefits patients and their families directly, as well as improves the likelihood of detecting efficacy in clinical trials. This issue of heterogeneity is not unique to SCI. In fields such as traumatic brain injury, Parkinson's disease, and amyotrophic lateral sclerosis, one approach to understand variability in recovery has been to make clinical trial data widely available to the greater research community. We contend that the SCI community should adopt a similar approach in providing open access clinical trial data.
Shin, Ji Cheol; Yu, Su Jin; Yang, Hea Eun; Yoon, Seo Yeon
Objective To evaluate the epidemiologic change of patients with spinal cord injury who were admitted to a Rehabilitation Hospital, Yonsei University College of Medicine, during 1987-1996 and 2004-2008. Methods Medical records of 629 patients with spinal cord injury admitted to the Rehabilitation Hospital, Yonsei University College of Medicine, from 2004 to 2008 were collected and reviewed retrospectively. Results The male-to-female ratio decreased to 2.86:1, the mean age at injury increased, nontraumatic etiology increased, traffic accident remained to be the most common in traumatic spinal cord injury, and falling increased significantly. Tumor was the most common etiology in nontraumatic spinal cord injury, tetraplegia and incomplete injuries occurred more than paraplegia and complete injuries, indwelling catheter was the most common voiding method, and the duration of hospitalization decreased. Conclusion Many trends changed in epidemiology of spinal cord injury. PMID:23525183
Shank, C D; Walters, B C; Hadley, M N
Acute traumatic spinal cord injury (SCI) is a devastating disease process affecting tens of thousands of people across the USA each year. Despite the increase in primary prevention measures, such as educational programs, motor vehicle speed limits, automobile running lights, and safety technology that includes automobile passive restraint systems and airbags, SCIs continue to carry substantial permanent morbidity and mortality. Medical measures implemented following the initial injury are designed to limit secondary insult to the spinal cord and to stabilize the spinal column in an attempt to decrease devastating sequelae. This chapter is an overview of the contemporary management of an acute traumatic SCI patient from the time of injury through the stay in the intensive care unit. We discuss initial triage, immobilization, and transportation of the patient by emergency medical services personnel to a definitive treatment facility. Upon arrival at the emergency department, we review initial trauma protocols and the evidence-based recommendations for radiographic evaluation of the patient's vertebral column. Finally, we outline closed cervical spine reduction and various aggressive medical therapies aimed at improving neurologic outcome.
Powell, Aaron; Davidson, Loren
In this article, an overview is provided of pediatric spinal cord injury, organized by effects of this injury on various organ systems. Specific management differences between children and adults with spinal cord injury are highlighted. A detailed management approach is offered for particularly complex topics, such as spasticity and upper extremity reconstruction.
Lee, Thay Q; McMahon, Patrick J
After spinal cord injury, excessive burden falls on the upper extremity, especially the shoulder. Overall, 51% of persons with spinal cord injury have shoulder problems. Common shoulder problems in persons with spinal cord injury begin with muscle imbalance that can lead to glenohumeral instability, impingement disease, rotator cuff tears, and subsequent degenerative joint disease. These problems can be attributed to the functional demands placed on the shoulder that are specific to patients with spinal cord injury, including overhead activities, wheelchair use, and transfers. Despite preventive exercises, shoulder problems in persons with spinal cord injury remain a significant problem, causing pain and functional limitations. The biomechanics of the shoulder for persons with spinal cord injury resulting from changes in muscle plasticity will be elucidated. Specifically, the effects of scapular protraction that can result from muscle imbalance, the age-dependent properties of the anterior band of the inferior glenohumeral ligament, and the influence of the dynamic restraints around the shoulder will be addressed.
Galeiras Vázquez, R; Ferreiro Velasco, M E; Mourelo Fariña, M; Montoto Marqués, A; Salvador de la Barrera, S
Traumatic spinal cord injury requires a multidisciplinary approach both for specialized treatment of the acute phase and for dealing with the secondary complications. A suspicion or diagnosis of spinal cord injury is the first step for a correct management. A review is made of the prehospital management and characteristics of the acute phase of spinal cord injury. Respiratory monitoring for early selective intubation, proper identification and treatment of neurogenic shock are essential for the prevention of secondary spinal cord injury. The use of corticosteroids is currently not a standard practice in neuroprotective treatment, and hemodynamic monitoring and early surgical decompression constitute the cornerstones of adequate management. Traumatic spinal cord injury usually occurs as part of multiple trauma, and this can make diagnosis difficult. Neurological examination and correct selection of radiological exams prevent delayed diagnosis of spinal cord injuries, and help to establish the prognosis.
Spinal Cord Injury PRINCIPAL INVESTIGATOR: Eva G. Widerström-Noga, DDS, PhD CONTRACTING ORGANIZATION: University of Miami REPORT...AND SUBTITLE Experiences of Living with Pain after a Spinal Cord Injury 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0465 5c. PROGRAM...after a spinal cord injury (SCI), with about two-thirds of persons with SCI reporting persistent pain despite available treatments. There is a risk
Donner, T R; Kline, D G
Eighty-three consecutive patients with extracranial accessory nerve injury seen over a 12-year period are reviewed. The most common etiology was iatrogenic injury to the nerve at the time of previous surgery. Such operations were usually minor in nature and often related to lymph node or benign tumor removal. Examination usually distinguished winging due to trapezius weakness from that of serratus anterior palsy. Trapezius weakness was seen in all cases. Sternocleidomastoid weakness was unusual. Patients with accessory palsy were evaluated by both clinical and electromyographic studies. Patients who exhibited no clinical or electrical evidence of regeneration were operated on (44 cases). Based on intraoperative nerve action potential studies, 8 lesions in continuity had neurolysis alone. Resection with repair either by end-to-end suture or by grafts was necessary in 31 cases. One case had suture removed from nerve, two had nerve placed into target muscle, and two had more proximal neurotization. Function was usually improved in both operative and nonoperative patients. Related anatomy is discussed.
Curt, Armin; Friston, Karl; Thompson, Alan
Traumatic spinal cord injury is often disabling and recovery of function is limited. As a consequence of damage, both spinal cord and brain undergo anatomical and functional changes. Besides clinical measures of recovery, biomarkers that can detect early anatomical and functional changes might be useful in determining clinical outcome—during the course of rehabilitation and recovery—as well as furnishing a tool to evaluate novel treatment interventions and their mechanisms of action. Recent evidence suggests an interesting three-way relationship between neurological deficit and changes in the spinal cord and of the brain and that, importantly, noninvasive magnetic resonance imaging techniques, both structural and functional, provide a sensitive tool to lay out these interactions. This review describes recent findings from multimodal imaging studies of remote anatomical changes (i.e., beyond the lesion site), cortical reorganization, and their relationship to clinical disability. These developments in this field may improve our understanding of effects on the nervous system that are attributable to the injury itself and will allow their distinction from changes that result from rehabilitation (i.e., functional retraining) and from interventions affecting the nervous system directly (i.e., neuroprotection or regeneration). PMID:22730072
Qiu, Feng; Yang, Jin-Cheng; Ma, Xiang-Yang; Xu, Jun-Jie; Yang, Qing-Lei; Zhou, Xin; Xiao, Yao-Sheng; Hu, Hai-Sheng; Xia, Li-Hui
Vertebral column resection is associated with a risk of spinal cord injury. In the present study, using a goat model, we aimed to investigate the relationship between changes in spinal cord volume and spinal cord injury due to spinal shortening, and to quantify the spinal cord volume per 1-mm height in order to clarify a safe limit for shortening. Vertebral column resection was performed at T10 in 10 goats. The spinal cord was shortened until the somatosensory-evoked potential was decreased by 50% from the baseline amplitude or delayed by 10% relative to the baseline peak latency. A wake-up test was performed, and the goats were observed for two days postoperatively. Magnetic resonance imaging was used to measure the spinal cord volume, T10 height, disc height, osteotomy segment height, and spinal segment height pre- and postoperatively. Two of the 10 goats were excluded, and hence, only data from eight goats were analyzed. The somatosensory-evoked potential of these eight goats demonstrated meaningful changes. With regard to neurologic function, five and three goats were classified as Tarlov grades 5 and 4 at two days postoperatively. The mean shortening distance was 23.6 ± 1.51 mm, which correlated with the d-value (post-pre) of the spinal cord volume per 1-mm height of the osteotomy segment (r = 0.95, p < 0.001) and with the height of the T10 body (r = 0.79, p = 0.02). The mean d-value (post-pre) of the spinal cord volume per 1-mm height of the osteotomy segment was 142.87 ± 0.59 mm3 (range, 142.19–143.67 mm3). The limit for shortening was approximately 106% of the vertebral height. The mean volumes of the osteotomy and spinal segments did not significantly change after surgery (t = 0.310, p = 0.765 and t = 1.241, p = 0.255, respectively). Thus, our results indicate that the safe limit for shortening can be calculated using the change in spinal cord volume per 1-mm height. PMID:26001196
Nowadays there are at present no efficient therapies for spinal cord injury (SCI), and new approaches have to be proposed. Recently, a new regenerative medicine strategy has been suggested using smart biomaterials able to carry and deliver cells and/or drugs in the damaged spinal cord. Among the wide field of emerging materials, research has been focused on hydrogels, three-dimensional polymeric networks able to swell and absorb a large amount of water. The present paper intends to give an overview of a wide range of natural, synthetic, and composite hydrogels with particular efforts for the ones studied in the last five years. Here, different hydrogel applications are underlined, together with their different nature, in order to have a clearer view of what is happening in one of the most sparkling fields of regenerative medicine. PMID:22816020
Anwar, M. Akhtar; Al Shehabi, Tuqa S.; Eid, Ali H.
Spinal cord injury (SCI) and spinal infarction lead to neurological complications and eventually to paraplegia or quadriplegia. These extremely debilitating conditions are major contributors to morbidity. Our understanding of SCI has certainly increased during the last decade, but remains far from clear. SCI consists of two defined phases: the initial impact causes primary injury, which is followed by a prolonged secondary injury consisting of evolving sub-phases that may last for years. The underlying pathophysiological mechanisms driving this condition are complex. Derangement of the vasculature is a notable feature of the pathology of SCI. In particular, an important component of SCI is the ischemia-reperfusion injury (IRI) that leads to endothelial dysfunction and changes in vascular permeability. Indeed, together with endothelial cell damage and failure in homeostasis, ischemia reperfusion injury triggers full-blown inflammatory cascades arising from activation of residential innate immune cells (microglia and astrocytes) and infiltrating leukocytes (neutrophils and macrophages). These inflammatory cells release neurotoxins (proinflammatory cytokines and chemokines, free radicals, excitotoxic amino acids, nitric oxide (NO)), all of which partake in axonal and neuronal deficit. Therefore, our review considers the recent advances in SCI mechanisms, whereby it becomes clear that SCI is a heterogeneous condition. Hence, this leads towards evidence of a restorative approach based on monotherapy with multiple targets or combinatorial treatment. Moreover, from evaluation of the existing literature, it appears that there is an urgent requirement for multi-centered, randomized trials for a large patient population. These clinical studies would offer an opportunity in stratifying SCI patients at high risk and selecting appropriate, optimal therapeutic regimens for personalized medicine. PMID:27147970
Khalatbary, Ali Reza
Polyphenols have been shown to have some of the neuroprotective effects against neurodegenerative diseases. These effects are attributed to a variety of biological activities, including free radical scavenging/antioxidant and anti-inflammatory and anti-apoptotic activities. In this regard, many efforts have been made to study the effects of various well-known dietary polyphenols on spinal cord injury (SCI) and to explore the mechanisms behind the neuroprotective effects. The aim of this paper is to present the mechanisms of neuroprotection of natural polyphenols used in animal models of SCI. PMID:24842137
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,…
Ha, Kee-Yong; Kim, Sang-Il
Spinal cord injury (SCI) has been considered an incurable condition and it often causes devastating sequelae. In terms of the pathophysiology of SCI, reducing secondary damage is the key to its treatment. Various researches and clinical trials have been performed, and some of them showed promising results; however, there is still no gold standard treatment with sufficient evidence. Two therapeutic concepts for SCI are neuroprotective and neuroregenerative strategies. The neuroprotective strategy modulates the pathomechanism of SCI. The purpose of neuroprotective treatment is to minimize secondary damage following direct injury. The aim of neuroregenerative treatment is to enhance the endogenous regeneration process and to alter the intrinsic barrier. With advancement in biotechnology, cell therapy using cell transplantation is currently under investigation. This review discusses the pathophysiology of SCI and introduces the therapeutic candidates that have been developed so far. PMID:28261421
nociceptive stimuli culminates in profound debilitating pain that serves no adaptive purpose for the sufferer. It is now established that spinal...Award Number: W81XWH-11-1-0806 TITLE: Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain Treatment...Sep 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain
Taweel, Waleed Al; Seyam, Raouf
Neurogenic bladder dysfunction due to spinal cord injury poses a significant threat to the well-being of patients. Incontinence, renal impairment, urinary tract infection, stones, and poor quality of life are some complications of this condition. The majority of patients will require management to ensure low pressure reservoir function of the bladder, complete emptying, and dryness. Management typically begins with anticholinergic medications and clean intermittent catheterization. Patients who fail this treatment because of inefficacy or intolerability are candidates for a spectrum of more invasive procedures. Endoscopic managements to relieve the bladder outlet resistance include sphincterotomy, botulinum toxin injection, and stent insertion. In contrast, patients with incompetent sphincters are candidates for transobturator tape insertion, sling surgery, or artificial sphincter implantation. Coordinated bladder emptying is possible with neuromodulation in selected patients. Bladder augmentation, usually with an intestinal segment, and urinary diversion are the last resort. Tissue engineering is promising in experimental settings; however, its role in clinical bladder management is still evolving. In this review, we summarize the current literature pertaining to the pathology and management of neurogenic bladder dysfunction in patients with spinal cord injury. PMID:26090342
Partida, Elizabeth; Mironets, Eugene; Hou, Shaoping; Tom, Veronica J.
Both sensorimotor and autonomic dysfunctions often occur after spinal cord injury (SCI). Particularly, a high thoracic or cervical SCI interrupts supraspinal vasomotor pathways and results in disordered hemodynamics due to deregulated sympathetic outflow. As a result of the reduced sympathetic activity, patients with SCI may experience hypotension, cardiac dysrhythmias, and hypothermia post-injury. In the chronic phase, changes within the CNS and blood vessels lead to orthostatic hypotension and life-threatening autonomic dysreflexia (AD). AD is characterized by an episodic, massive sympathetic discharge that causes severe hypertension associated with bradycardia. The syndrome is often triggered by unpleasant visceral or sensory stimuli below the injury level. Currently the only treatments are palliative – once a stimulus elicits AD, pharmacological vasodilators are administered to help reduce the spike in arterial blood pressure. However, a more effective means would be to mitigate AD development by attenuating contributing mechanisms, such as the reorganization of intraspinal circuits below the level of injury. A better understanding of the neuropathophysiology underlying cardiovascular dysfunction after SCI is essential to better develop novel therapeutic approaches to restore hemodynamic performance. PMID:27073353
Gwak, Young S.; Hulsebosch, Claire E.
Spinal cord injury induces maladaptive synaptic transmission in the somatosensory system that results in chronic central neuropathic pain. Recent literature suggests that glial-neuronal interactions are important modulators in synaptic transmission following spinal cord injury. Neuronal hyperexcitability is one of the predominant phenomenon caused by maladaptive synaptic transmission via altered glial-neuronal interactions after spinal cord injury. In the somatosensory system, spinal inhibitory neurons counter balance the enhanced synaptic transmission from peripheral input. For a decade, the literature suggests that hypofunction of GABAergic inhibitory tone is an important factor in the enhanced synaptic transmission that often results in neuronal hyperexcitability in dorsal horn neurons following spinal cord injury. Neurons and glial cells synergistically control intracellular chloride ion gradients via modulation of chloride transporters, extracellular glutamate and GABA concentrations via uptake mechanisms. Thus, the intracellular “GABA-glutamate-glutamine cycle” is maintained for normal physiological homeostasis. However, hyperexcitable neurons and glial activation after spinal cord injury disrupts the balance of chloride ions, glutamate and GABA distribution in the spinal dorsal horn and results in chronic neuropathic pain. In this review, we address spinal cord injury induced mechanisms in hypofunction of GABAergic tone that results in chronic central neuropathic pain. PMID:21216257
Paul, Ian; Reichard, R Ross
Subacute combined degeneration (SCD) of the spinal cord is the most common neurologic manifestation of vitamin B12 (cobalamin) deficiency and is usually secondary to autoimmune gastritis, but may also be seen in malnutrition syndromes such as chronic alcoholism, strict vegetarianism, gastrectomy, and also in nitrous oxide abuse. Although traumatic spinal cord injury is routinely encountered in the medical examiner's office, medical causes of spinal cord abnormalities such as SCD should be considered in the appropriate clinical setting. We report a case of alcohol-associated SCD mimicking traumatic spinal cord injury.
Biering-Sørensen, Fin; Biering-Sørensen, Tor; Liu, Nan; Malmqvist, Lasse; Wecht, Jill Maria; Krassioukov, Andrei
A spinal cord injury (SCI) interferes with the autonomic nervous system (ANS). The effect on the cardiovascular system will depend on the extent of damage to the spinal/central component of ANS. The cardiac changes are caused by loss of supraspinal sympathetic control and relatively increased parasympathetic cardiac control. Decreases in sympathetic activity result in heart rate and the arterial blood pressure changes, and may cause arrhythmias, in particular bradycardia, with the risk of cardiac arrest in those with cervical or high thoracic injuries. The objective of this review is to give an update of the current knowledge related to the alterations in cardiac autonomic control following SCI. With this purpose the review includes the following subheadings: 2. Neuro-anatomical plasticity and cardiac control 2.1 Autonomic nervous system and the heart 2.2 Alteration in autonomic control of the heart following spinal cord injury 3. Spinal shock and neurogenic shock 3.1 Pathophysiology of spinal shock 3.2 Pathophysiology of neurogenic shock 4. Autonomic dysreflexia 4.1 Pathophysiology of autonomic dysreflexia 4.2 Diagnosis of autonomic dysreflexia 5. Heart rate/electrocardiography following spinal cord injury 5.1 Acute phase 5.2 Chronic phase 6. Heart rate variability 6.1 Time domain analysis 6.2 Frequency domain analysis 6.3 QT-variability index 6.4 Nonlinear (fractal) indexes 7. Echocardiography 7.1 Changes in cardiac structure following spinal cord injury 7.2 Changes in cardiac function following spinal cord injury 8. International spinal cord injury cardiovascular basic data set and international standards to document the remaining autonomic function in spinal cord injury.
Goldcamp, E. Michael; Myers, John; Hendricks, Kitty; Layne, Larry; Helmkamp, Jim
Use of all-terrain vehicles (ATVs) in agriculture appears to be growing. Purpose: To provide estimates of ATV ownership and exposure on US farms and an overview of injuries to youths as a result of ATV use on the farm in 2001. Methods: Analysis of the National Institute for Occupational Safety and Health and US Department of Agriculture 2001…
injury . They will supervise the creation of the cervical spine injuries , care of the animals, sacrifice and perfusion fixation, and, after completion...cord injury . They will supervise the creation of the cervical spine injuries , care of the animals, sacrifice and perfusion fixation, and, after...AWARD NUMBER: W81XWH-10-1-0715 TITLE: Magnetic Resonance Characterization of Axonal Response to Spinal Cord Injury PRINCIPAL INVESTIGATOR
Ho, Chester H.; Triolo, Ronald J.; Elias, Anastasia L.; Kilgore, Kevin L.; DiMarco, Anthony F.; Bogie, Kath; Vette, Albert H.; Audu, Musa; Kobetic, Rudi; Chang, Sarah R.; Chan, K. Ming; Dukelow, Sean; Bourbeau, Dennis J.; Brose, Steven W.; Gustafson, Kenneth J.; Kiss, Zelma; Mushahwar, Vivian K.
Synopsis Spinal cord injuries (SCI) can disrupt communications between the brain and the body, leading to a loss of control over otherwise intact neuromuscular systems. The use of electrical stimulation (ES) of the central and peripheral nervous system can take advantage of these intact neuromuscular systems to provide therapeutic exercise options, to allow functional restoration, and even to manage or prevent many medical complications following SCI. The use of ES for the restoration of upper extremity, lower extremity and truncal functions can make many activities of daily living a potential reality for individuals with SCI. Restoring bladder and respiratory functions and preventing pressure ulcers may significantly decrease the morbidity and mortality following SCI. Many of the ES devices are already commercially available and should be considered by all SCI clinicians routinely as part of the lifelong rehabilitation care plan for all eligible individuals with SCI. PMID:25064792
Bazilevskaia, Z V; Golovnykh, L L; Kirkinskaia, T A
In a group of 520 patients with injury to the spine and spinal cord 125 died within 10 years. The highest fatality rate (76.0 +/0 3.8) is recorded in the first year after the injury. In the following 10 years the fatality rate was uniform and ranged between 1.6 and 4.1%. This value increases with the patient's age, the severity of the spinal cord injury, and the degree of damage to the spinal ligamento-bursal apparatus. Among the total number of injured, 76% have a survival period of more than 10 years.
Krause, James S.; Saunders, Lee; Staten, David
The objective of this article was to identify the relationship between race-ethnicity and employment after spinal cord injury (SCI), while evaluating interrelationships with gender, injury severity, and education. The authors used a cohort design using the most current status from a post-injury interview from the National SCI Statistical Center.…
Ueno, Masaki; Ueno-Nakamura, Yuka; Niehaus, Jesse; Popovich, Phillip G.; Yoshida, Yutaka
Spinal cord injury (SCI) at high spinal levels (e.g., above thoracic level 5) causes systemic immune suppression; however, the underlying mechanisms are unknown. Here, we show that profound plasticity develops within spinal autonomic circuitry below the injury, creating a sympathetic anti-inflammatory reflex, and that chemogenetic silencing of this reflex circuitry blocks post-SCI immune suppression. These data provide new insights and potential therapeutic options for limiting the devastating consequences of post-traumatic autonomic hyperreflexia and post-injury immune suppression. PMID:27089020
Whole body /sup 99m/T-pyrophosphate bone scans were obtained and correlated with skeletal radiographs for detection of heterotopic ossification in 135 spinal injury patients. There were 40 patients with recent injury (less than 6 months) and 95 with injury of over 6 months duration. Heterotopic new bone was detected on the bone scan in 33.7% of 95 patients with spinal cord injuries of more than 6 months duration and 30% of 40 patients with injuries of less than 6 months. The radionuclide scan was found to be useful in detection of heterotopic ossification at its early stage and in its differentiation from other complications in spinal cord injury patients.
White-Schenk, Désirée; Shi, Riyi; Leary, James F
Neurological injury, such as spinal cord injury, has a secondary injury associated with it. The secondary injury results from the biological cascade after the primary injury and affects previous uninjured, healthy tissue. Therefore, the mitigation of such a cascade would benefit patients suffering a primary injury and allow the body to recover more quickly. Unfortunately, the delivery of effective therapeutics is quite limited. Due to the inefficient delivery of therapeutic drugs, nanoparticles have become a major field of exploration for medical applications. Based on their material properties, they can help treat disease by delivering drugs to specific tissues, enhancing detection methods, or a mixture of both. Incorporating nanomedicine into the treatment of neuronal injury and disease would likely push nanomedicine into a new light. This review highlights the various pathological issues involved in secondary spinal cord injury, current treatment options, and the improvements that could be made using a nanomedical approach. PMID:25673988
bladder distention between spinal intact and spinal cord injury ...excitability of bladder afferent neurons in rats with spinal cord injury : a role of A-type voltage-gated potassium channels. 110th Annual Meeting AUA...Increased excitability of bladder afferent neurons in rats with spinal cord injury : a role of A-type voltage-gated potassium channels. 110th Annual
pathophysiological basis of neurogenic detrusor overactivity with spinal cord injury (SCI). However, the... bladder distention after SCI. Using adult female rats with chronic spinal cord injury induced by Th4 spinal cord transection, we will investigate: (1...autonomic dysreflexia during bladder distention in rats with spinal cord injury . 111th Annual Meeting AUA, Abstract No. 34, San Diego, May 4-8, 2013.
Spinal cord injury research has greatly expanded in recent years, but our understanding of the mechanisms that underlie the functional recovery that can occur over the weeks and months following the initial injury, is far from complete. To grasp the scope of the problem, it is important to begin by defining the sensorimotor pathways that might be involved by a spinal injury. This is done in the rodent and nonhuman primate, which are two of the most commonly used animal models in basic and translational spinal injury research. Many of the better known experimentally induced models are then reviewed in terms of the pathways they involve and the reorganization and recovery that have been shown to follow. The better understood neuronal mechanisms mediating such post-injury plasticity, including dendritic spine growth and axonal sprouting, are then examined. PMID:19307422
Tator, C. H.; Edmonds, V. E.
There has been an alarming increase in the number of spinal injuries in hockey players. Between 1976 and 1983, 42 were reported to the Committee on Prevention of Spinal Injuries due to Hockey. The median age of the injured players was 17 years. Of the 42 players 28 had spinal cord injuries, and 17 of them had complete paralysis below the vertebral level of the injury. Strikes from behind and collisions with the boards were common mechanisms of injury. Many of the players had suffered a burst fracture of the cervical spine following a blow to the top of the helmet when the neck was slightly flexed. The committee studied a number of possible etiologic factors and made several recommendations regarding prevention. League officials, coaches, players and equipment manufacturers can all play a role in prevention. Images Fig. 1 Fig. 2 PMID:6704840
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.
Cohen, Avis [University of Maryland, College Park, Maryland, United States
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.
Kim, Hee Yul; Ju, Chang Il; Kim, Seok Won
We report an extremely rare case of traumatic cervical spinal subdural hematoma not related to intracranial injury. There has been no report on traumatic cervical spinal subdrual hematoma not related to intracranial injury. A 27-year-old female patient was admitted to our emergency room due to severe neck pain and right arm motor weakness after car collision. On admission, she presented with complete monoplegia and hypoesthesia of right arm. Magnetic resonance imaging (MRI) revealed subdural hematoma compressing spinal cord. Lumbar cerebrospinal fluid (CSF) analysis revealed 210,000 red blood cells/mm(3). She was managed conservatively by administrations of steroid pulse therapy and CSF drainage. Her muscle power of right arm improved to a Grade III 16 days after admission. Follow-up MRI taken 16th days after admission revealed almost complete resolution of the hematoma. Here, the authors report a traumatic cervical spinal SDH not associated with intracranial injury.
Serradj, Najet; Agger, Sydney F; Hollis, Edmund R
Restoring corticospinal function after spinal cord injury is a significant challenge as the corticospinal tract elicits no substantive, spontaneous regeneration, and its interruption leaves a permanent deficit. The corticospinal circuit serves multiple motor and sensory functions within the mammalian nervous system as the direct link between isocortex and spinal cord. Maturation of the corticospinal circuit involves the refinement of projections within the spinal cord and a subsequent refinement of motor maps within the cortex. The plasticity of these cortical motor maps mirrors the acquisition of skilled motor learning, and both the maps and motor skills are disrupted following injury to the corticospinal tract. The motor cortex exhibits the capacity to incorporate changes in corticospinal projections induced by both spontaneous and therapeutic-mediated plasticity of corticospinal axons through appropriate rehabilitation. An understanding of the mechanisms of corticospinal plasticity in motor learning will undoubtedly help inform strategies to improve motor rehabilitation after spinal cord injury.
Progress in the care of people with spinal cord injury (SCI) spans every aspect, from research in neuroregeneration to pharmacologic interventions. This article focuses on advances in rehabilitation interventions, which have employed bioengineering, computerization, and advanced therapeutic techniques. These interventions are being applied to functional deficits of the bladder, bowel, upper extremities, and respiratory system, as well as to improvements in ambulation and mobility. Functional electrical stimulation (FES) is being used to augment the function of the lower extremities, the upper extremities (Freehand System), and the bowel and bladder (Vocare System). Tendon transfer is a reconstructive technique used to improve upper extremity function; it is sometimes combined with FES. Body weight-supported treadmill training is being used to improve ambulation in people with incomplete SCI, and advances in wheelchair technology are expanding options for mobility. Cushion design and pressure mapping are modalities being used to reduce the high risk for pressure ulcers in the SCI population. Research on shoulder stressors is being applied to transfer techniques, exercise regimens, adaptive equipment and wheelchair mechanics to minimize shoulder pain, another common complication. The effectiveness of rehabilitation interventions needs to be documented by evidence-based research. Researchers are focusing on the identification of outcomes measures that will form the basis for established standards of care for individuals with SCI. Perhaps the combination of conventional and newer therapies may enhance neurological recovery. Well-designed studies are needed before we can make this determination.
Bauman, William A; Cardozo, Christopher P
The pathophysiology, clinical considerations, and relevant experimental findings with regard to osteoporosis in individuals with spinal cord injury (SCI) will be discussed. The bone loss that occurs acutely after more neurologically motor complete SCI is unique for its sublesional skeletal distribution and rate, at certain skeletal sites approaching 1% of bone mineral density per week, and its resistance to currently available treatments. The areas of high bone loss include the distal femur, proximal tibia, and more distal boney sites. Evidence from a study performed in monozygotic twins discordant for SCI indicates that sublesional bone loss in the twin with SCI increases for several decades, strongly suggesting that the heightened net bone loss after SCI may persist for an extended period of time. The increased frequency of fragility fracture after paralysis will be discussed, and a few risk factors for such fractures after SCI will be examined. Because vitamin D deficiency, regardless of disability, is a relevant consideration for bone health, as well as an easily reversible condition, the increased prevalence of and treatment target values for vitamin D in this deficiency state in the SCI population will be reviewed. Pharmacological and mechanical approaches to preserving bone integrity in persons with acute and chronic SCI will be reviewed, with emphasis placed on efficacy and practicality. Emerging osteoanabolic agents that improve functioning of WNT/β-catenin signaling after paralysis will be introduced as therapeutic interventions that may hold promise.
Kan, E M; Ling, E A; Lu, J
Spinal cord injury (SCI) damages axons and disrupts myelination interrupting sensory and motor neuronal transmission to and from the brain. Patients suffering from SCI although continue to survive, are often left chronically disabled and with no promise of a cure. Advances in stem cell biology has opened up doors for the use of human embryonic, adult neural and induced pluripotent stem cell strategies for SCI. Despite great promise from animal research, clinical trials have been limited and the jury is still out on its safety and efficacy. This review discusses the advantages and disadvantages of the various stem cell types, barriers hindering translation from animal to humans, and the need for established guidelines for standardization of clinical trials ensuring subsequent implementation. Ultimately, unrealistic expectations of stem cell therapy (SCT) as the elixir for SCI should be managed. The success of SCT for SCI lies in the network of research scientists, medical professionals and patients working cooperatively to build up a knowledge-intensive platform for a comprehensive risk-benefit assessment of SCT for SCI.
Teasell, R.W.; Hsieh, T.J.; Aubut, JA. L.; Eng, J.J.; Krassioukov, A.; Tu, L.
Objective To systematically review the published literature on the treatment of deep venous thromboembolism post-spinal cord injury (SCI). Data Sources MEDLINE/Pubmed, CINAHL, EMBASE, and PsycINFO databases were searched for articles addressing the treatment of deep venous thromboembolism post-SCI. Randomized controlled trials (RCTs) were assessed for methodologic quality using the Physiotherapy Evidence Database Scale, while non-RCTs were assessed using the Downs and Black evaluation tool. Study Selection Studies included RCTs, non-RCTS, cohort, case-control, case series, pre-post, and postinterventional studies. Case studies were included only when no other studies were available. Data Extraction Data extracted included demographics, the nature of the study intervention, and study results. Data Synthesis Levels of evidence were assigned to the interventions using a modified Sackett scale. Conclusions Twenty-three studies met inclusion criteria. Thirteen studies examined various pharmacologic interventions for the treatment or prevention of deep venous thrombosis in SCI patients. There was strong evidence to support the use of low molecular weight heparin in reducing venous thrombosis events, and a higher adjusted dose of unfractionated heparin was found to be more effective than 5000 units administered every 12 hours, although bleeding complication was more common. Nonpharmacologic treatments were also reviewed, but again limited evidence was found to support these treatments. PMID:19236977
Sezer, Nebahat; Akkuş, Selami; Uğurlu, Fatma Gülçin
Spinal cord injury (SCI) is a serious medical condition that causes functional, psychological and socioeconomic disorder. Therefore, patients with SCI experience significant impairments in various aspects of their life. The goals of rehabilitation and other treatment approaches in SCI are to improve functional level, decrease secondary morbidity and enhance health-related quality of life. Acute and long-term secondary medical complications are common in patients with SCI. However, chronic complications especially further negatively impact on patients’ functional independence and quality of life. Therefore, prevention, early diagnosis and treatment of chronic secondary complications in patients with SCI is critical for limiting these complications, improving survival, community participation and health-related quality of life. The management of secondary chronic complications of SCI is also important for SCI specialists, families and caregivers as well as patients. In this paper, we review data about common secondary long-term complications after SCI, including respiratory complications, cardiovascular complications, urinary and bowel complications, spasticity, pain syndromes, pressure ulcers, osteoporosis and bone fractures. The purpose of this review is to provide an overview of risk factors, signs, symptoms, prevention and treatment approaches for secondary long-term complications in patients with SCI. PMID:25621208
Heinemann, Allen; And Others
Hope has motivational importance to individuals who have suffered a major physical loss. Theories of adjustment to a spinal cord injury take one of three approaches: (1) premorbid personality, which highlights the individual's past experiences, personal meanings, and body image; (2) typologies of injury reactions, which range from normal to…
Anson, C. A.; Shepherd, C.
Data from 348 patients (mean age 37) with postacute spinal cord injury revealed that 95% reported at least 1 secondary problem, and 58% reported 3 or more. The number and severity of complications varied with time since the injury. Obesity, pain, spasticity, urinary tract infections, pressure sores, and lack of social integration were common…
Martinez, Marina; Delivet-Mongrain, Hugo; Rossignol, Serge
After a spinal hemisection at thoracic level in cats, the paretic hindlimb progressively recovers locomotion without treadmill training but asymmetries between hindlimbs persist for several weeks and can be seen even after a further complete spinal transection at T13. To promote optimal locomotor recovery after hemisection, such asymmetrical changes need to be corrected. In the present study we determined if the locomotor deficits induced by a spinal hemisection can be corrected by locomotor training and, if so, whether the spinal stepping after the complete spinal cord transection is also more symmetrical. This would indicate that locomotor training in the hemisected period induces efficient changes in the spinal cord itself. Sixteen adult cats were first submitted to a spinal hemisection at T10. One group received 3 wk of treadmill training, whereas the second group did not. Detailed kinematic and electromyographic analyses showed that a 3-wk period of locomotor training was sufficient to improve the quality and symmetry of walking of the hindlimbs. Moreover, after the complete spinal lesion was performed, all the trained cats reexpressed bilateral and symmetrical hindlimb locomotion within 24 h. By contrast, the locomotor pattern of the untrained cats remained asymmetrical, and the hindlimb on the side of the hemisection was still deficient. This study highlights the beneficial role of locomotor training in facilitating bilateral and symmetrical functional plastic changes within the spinal circuitry and in promoting locomotor recovery after an incomplete spinal cord injury.
Jacobs, Patrick L; Nash, Mark S
Persons with spinal cord injury (SCI) exhibit deficits in volitional motor control and sensation that limit not only the performance of daily tasks but also the overall activity level of these persons. This population has been characterised as extremely sedentary with an increased incidence of secondary complications including diabetes mellitus, hypertension and atherogenic lipid profiles. As the daily lifestyle of the average person with SCI is without adequate stress for conditioning purposes, structured exercise activities must be added to the regular schedule if the individual is to reduce the likelihood of secondary complications and/or to enhance their physical capacity. The acute exercise responses and the capacity for exercise conditioning are directly related to the level and completeness of the spinal lesion. Appropriate exercise testing and training of persons with SCI should be based on the individual's exercise capacity as determined by accurate assessment of the spinal lesion. The standard means of classification of SCI is by application of the International Standards for Classification of Spinal Cord Injury, written by the Neurological Standards Committee of the American Spinal Injury Association. Individuals with complete spinal injuries at or above the fourth thoracic level generally exhibit dramatically diminished cardiac acceleration with maximal heart rates less than 130 beats/min. The work capacity of these persons will be limited by reductions in cardiac output and circulation to the exercising musculature. Persons with complete spinal lesions below the T(10) level will generally display injuries to the lower motor neurons within the lower extremities and, therefore, will not retain the capacity for neuromuscular activation by means of electrical stimulation. Persons with paraplegia also exhibit reduced exercise capacity and increased heart rate responses (compared with the non-disabled), which have been associated with circulatory limitations
Straley, Karin S.; Po Foo, Cheryl Wong
Abstract The highly debilitating nature of spinal cord injuries has provided much inspiration for the design of novel biomaterials that can stimulate cellular regeneration and functional recovery. Many experts agree that the greatest hope for treatment of spinal cord injuries will involve a combinatorial approach that integrates biomaterial scaffolds, cell transplantation, and molecule delivery. This manuscript presents a comprehensive review of biomaterial-scaffold design strategies currently being applied to the development of nerve guidance channels and hydrogels that more effectively stimulate spinal cord tissue regeneration. To enhance the regenerative capacity of these two scaffold types, researchers are focusing on optimizing the mechanical properties, cell-adhesivity, biodegradability, electrical activity, and topography of synthetic and natural materials, and are developing mechanisms to use these scaffolds to deliver cells and biomolecules. Developing scaffolds that address several of these key design parameters will lead to more successful therapies for the regeneration of spinal cord tissue. PMID:19698073
develop from 1) aberrant plasticity and 2) the loss of tonic input onto sympathetic preganglionic neurons (SPN) in the spinal cord that drive...life. Another cause of autonomic dysreflexia is aberrant plasticity of spinal circuits that increase activity of the sympathetic preganglionic neurons...modulatory circuitry and pharmacological mitigation of hyperexcitability resulting from aberrant plasticity will result in greater mitigation of
Treatment with the flavonoid quercetin starting 1 h after compression SCI in rats had a var- iable effect on improving locomotor function in that a...Kendall, E., Kamencic, H., Ghong, Z., Griebel, R.W., Juurlink, B.H., 2003. Quercetin promotes functional recovery following acute spinal cord injury. J...Neurotrauma 20 (6), 583-591. Schultke, E., Griebel, R.W., Juurlink, B.H., 2010a. Quercetin attenuates inflammatory pro- cesses after spinal cord
Freund, Patrick; Weiskopf, Nikolaus; Ward, Nick S; Hutton, Chloe; Gall, Angela; Ciccarelli, Olga; Craggs, Michael; Friston, Karl; Thompson, Alan J
The impact of traumatic spinal cord injury on structural integrity, cortical reorganization and ensuing disability is variable and may depend on a dynamic interaction between the severity of local damage and the capacity of the brain for plastic reorganization. We investigated trauma-induced anatomical changes in the spinal cord and brain, and explored their relationship to functional changes in sensorimotor cortex. Structural changes were assessed using cross-sectional cord area, voxel-based morphometry and voxel-based cortical thickness of T1-weighted images in 10 subjects with cervical spinal cord injury and 16 controls. Cortical activation in response to right-sided (i) handgrip; and (ii) median and tibial nerve stimulation were assessed using functional magnetic resonance imaging. Regression analyses explored associations between cord area, grey and white matter volume, cortical activations and thickness, and disability. Subjects with spinal cord injury had impaired upper and lower limb function bilaterally, a 30% reduced cord area, smaller white matter volume in the pyramids and left cerebellar peduncle, and smaller grey matter volume and cortical thinning in the leg area of the primary motor and sensory cortex compared with controls. Functional magnetic resonance imaging revealed increased activation in the left primary motor cortex leg area during handgrip and the left primary sensory cortex face area during median nerve stimulation in subjects with spinal cord injury compared with controls, but no increased activation following tibial nerve stimulation. A smaller cervical cord area was associated with impaired upper limb function and increased activations with handgrip and median nerve stimulation, but reduced activations with tibial nerve stimulation. Increased sensory deficits were associated with increased activations in the left primary sensory cortex face area due to median nerve stimulation. In conclusion, spinal cord injury leads to cord atrophy
Schomberg, Dominic T; Miranpuri, Gurwattan S; Chopra, Abhishek; Patel, Kush; Meudt, Jennifer J; Tellez, Armando; Resnick, Daniel K; Shanmuganayagam, Dhanansayan
Spinal cord injury (SCI) is a physically and psychologically devastating clinical condition. The typical treatment regimens of decompressive surgery and rehabilitation therapy still leave many patients with permanent disability. The development of new therapies and devices can be accelerated if relevant translational animal models are more effectively used in pre-clinical stages. Swine is a highly relevant model for SCI research, especially with respect to spine and spinal cord anatomy, spine vasculature, immune responses to injury, and functional assessments. Several spine injury models have recently been developed for swine and are beginning to be used to evaluate new therapies. Swine models of SCI offer tremendous advantages for efficient translation of pre-clinical discoveries and the development of new therapies and devices. Future swine models will also be enhanced by advances in gene-editing technology to further elucidate the complex pathophysiology associated with SCI and provide a means to engineer specific spinal pathologies.
Wang, Jian-wei; Yang, Jun-feng; Ma, Yong; Hua, Zhen; Guo, Yang; Gu, Xiao-lin; Zhang, Ya-feng
The mechanism involved in neural regeneration after spinal cord injury is unclear. The myelin-derived protein Nogo-A, which is specific to the central nervous system, has been identified to negatively affect the cytoskeleton and growth program of axotomized neurons. Studies have shown that Nogo-A exerts immediate and chronic inhibitory effects on neurite outgrowth. In vivo, inhibitors of Nogo-A have been shown to lead to a marked enhancement of regenerative axon extension. We established a spinal cord injury model in rats using a free-falling weight drop device to subsequently investigate Nogo-A expression. Nogo-A mRNA and protein expression and immunoreactivity were detected in spinal cord tissue using real-time quantitative PCR, immunohistochemistry and western blot analysis. At 24 hours after spinal cord injury, Nogo-A protein and mRNA expression was low in the injured group compared with control and sham-operated groups. The levels then continued to drop further and were at their lowest at 3 days, rapidly rose to a peak after 7 days, and then gradually declined again after 14 days. These changes were observed at both the mRNA and protein level. The transient decrease observed early after injury followed by high levels for a few days indicates Nogo-A expression is time dependent. This may contribute to the lack of regeneration in the central nervous system after spinal cord injury. The dynamic variation of Nogo-A should be taken into account in the treatment of spinal cord injury. PMID:25883620
Schrödel, M; Hertlein, H
Pediatric cervical spine injuries are rare. Knowledge of possible types of injury, physiological development and anomalies is necessary in order to not overlook the injury and to initiate suitable therapy. Description of the clinical assessment, Management of diagnostics and therapy of specific injuries. Based on a selective literature search and taking into consideration our own experience, typical injuries at the upper and lower cervical spine in pediatric patients are depicted. In the presence of neurological deficits, identification of the cause is crucial. Odontoid fractures and injuries to the second cervical vertebra are common in upper cervical spine injuries, compression fractures and facet joint dislocation injuries are common in lower cervical spine injuries. Depending on the location of the injury and on the grade of instability, specific therapy, including conservative treatment (orthosis, halo fixation) and operative treatment (internal fixation, fusion) might be necessary.
Quarrie, Kenneth L; Cantu, Robert C; Chalmers, David J
Injuries to the cervical spine are among the most serious injuries occurring as a result of participation in rugby. Outcomes of such injuries range from complete recovery to death, depending on the degree of spinal cord damage sustained. Much information has been gained regarding the mechanisms and frequency of such injuries, from case reports and case series studies. The most commonly reported mechanism of injury has been hyperflexion of the cervical spine, resulting in fracture dislocation of C4-C5 or C5-C6. Tracking both the trends of incidence of spinal injuries, and the effectiveness of injury prevention initiatives has proved difficult because of a lack of properly conducted epidemiological studies. Within the constraints of the research published to date, it appears that hookers and props have been at disproportionate risk of cervical spine injury, predominantly because of injuries sustained during scrummaging. While the scrum was the phase of play most commonly associated with spinal injuries throughout the 1980s in most rugby playing countries, there has been a trend through the 1990s of an increasing proportion of spinal injuries occurring in the tackle situation. The majority of injuries have occurred early in the season, when grounds tend to be harder, and players are lacking both practice and physical conditioning for the physical contact phases of the sport. A number of injury prevention measures have been launched, including changes to the laws of the game regarding scrummaging, and education programmes aimed at enforcing safe techniques and eliminating illegal play. Calls for case-registers and effective epidemiological studies have been made by researchers and physicians in most countries where rugby is widespread, but it appears to be only recently that definite steps have been made towards this goal. Well-designed epidemiological studies will be able to provide more accurate information about potential risk factors for injury such as age, grade
The World Health Organization together with the Iceland Ministry of Health and Social Security sponsored a conference entitled 'Human Spinal Cord Injury: New and Emerging Approaches to Treatment' held on May 31-June 2, 2001 in Reykjavik, Iceland. To help catalyze the development of new paradigms to address spinal cord injury, the conference's overall goal was to bring in a diversity of perspectives, ranging from state-of-the-art stem cell biology to the ancient wisdom of Eastern Medicine. The purpose of this paper is to summarize the presentations of the conference's 26 speakers.
Saxena, Tarun; Gilbert, Jeremy; Stelzner, Dennis; Hasenwinkel, Julie
The glial scar formed at the site of traumatic spinal cord injury (SCI) has been classically hypothesized to be a potent physical and biochemical barrier to nerve regeneration. One longstanding hypothesis is that the scar acts as a physical barrier due to its increased stiffness in comparison to uninjured spinal cord tissue. However, the information regarding the mechanical properties of the glial scar in the current literature is mostly anecdotal and not well quantified. We monitored the mechanical relaxation behavior of injured rat spinal cord tissue at the site of mid-thoracic spinal hemisection 2 weeks and 8 weeks post-injury using a microindentation test method. Elastic moduli were calculated and a modified standard linear model (mSLM) was fit to the data to estimate the relaxation time constant and viscosity. The SLM was modified to account for a spectrum of relaxation times, a phenomenon common to biological tissues, by incorporating a stretched exponential term. Injured tissue exhibited significantly lower stiffness and elastic modulus in comparison to uninjured control tissue, and the results from the model parameters indicated that the relaxation time constant and viscosity of injured tissue were significantly higher than controls. This study presents direct micromechanical measurements of injured spinal cord tissue post-injury. The results of this study show that the injured spinal tissue displays complex viscoelastic behavior, likely indicating changes in tissue permeability and diffusivity.
Vaidyanathan, Subramanian; Soni, Bakul M; Singh, Gurpreet; Oo, Tun; Hughes, Peter L
Intermittent catheterisation is the preferred method of managing the neurogenic bladder in patients with spinal cord injury. However, spinal cord physicians experienced problems when trying to implement an intermittent catheterisation regime in some spinal cord injury patients in the northwest of England. We present illustrative cases to describe practical difficulties encountered by patients while trying to adopt an intermittent catheterisation regime. Barriers to intermittent catheterisation are (1) caregivers or nurses are not available to carry out five or six catheterisations a day; (2) lack of time to perform intermittent catheterisations; (3) unavailability of suitable toilet facilities in public places, including restaurants and offices; (4) redundant prepuce in a male patient, which prevents ready access to urethral meatus; (5) urethral false passage; (6) urethral sphincter spasm requiring the use of flexible-tip catheters and á-adrenoceptor-blocking drugs; (7) reluctance to perform intermittent catheterisation in patients >60 years by some health professionals; and (8) difficulty in accessing the urethral meatus for catheterisation while the patient is sitting up, especially in female patients. These cases demonstrate the urgent need for provision of trained caregivers who can perform intermittent catheterisation, and improvement in public facilities that are suitable for performing catheterisation in spinal cord injury patients. Further, vigilance should be exercised during each catheterisation in order to prevent complications, such as urethral trauma and consequent false passages. Health professionals should make additional efforts to implement intermittent catheterisation in female spinal cord injury patients and in those >60 years.
individual. In addition, the immune genes that encode these key inflammatory mediators are highly polymorphic. Hence, an individual may have a genetic ...Critically, this genetic variability may significantly impact the long-term health and quality of life of the individual. Thus both genetics and drug...agents and genetic variability on the occurrence of chronic pain following spinal cord injury. KEYWORDS Pain, spinal cord injury, opioid, glia, innate
Sabapathy, Vikram; Tharion, George; Kumar, Sanjay
The spinal cord injury leads to enervation of normal tissue homeostasis ultimately leading to paralysis. Until now there is no proper cure for the treatment of spinal cord injury. Recently, cell therapy in animal spinal cord injury models has shown some progress of recovery. At present, clinical trials are under progress to evaluate the efficacy of cell transplantation for the treatment of spinal cord injury. Different types of cells such as pluripotent stem cells derived neural cells, mesenchymal stromal cells, neural stem cells, glial cells are being tested in various spinal cord injury models. In this review we highlight both the advances and lacuna in the field of spinal cord injury by discussing epidemiology, pathophysiology, molecular mechanism, and various cell therapy strategies employed in preclinical and clinical injury models and finally we discuss the limitations and ethical issues involved in cell therapy approach for treating spinal cord injury. PMID:26240569
Shields, Richard K
Spinal cord injury is associated with adaptations to the muscular, skeletal, and spinal systems. Experimental data are lacking regarding the extent to which rehabilitative methods may influence these adaptations. An understanding of the plasticity of the muscular, skeletal, and spinal systems after paralysis may be important as new rehabilitative technologies emerge in the 21st century. Moreover, individuals injured today may become poor candidates for future scientific advancements (cure) if their neuromusculoskeletal systems are irreversibly impaired. The primary purpose of this paper is to explore the physiological properties of skeletal muscle as a result of spinal cord injury; secondarily, to consider associated changes at the skeletal and spinal levels. Muscular adaptations include a transformation to faster myosin, increased contractile speeds, shift to the right on the torque-frequency curve, increased fatigue, and enhanced doublet potentiation. These muscular adaptations may be prevented in individuals with acute paralysis and partially reversed in individuals with chronic paralysis. Moreover, the muscular changes may be coordinated with motor unit and spinal circuitry adaptations. Concurrently, skeletal adaptations, as measured by bone mineral density, show extensive loss within the first six months after paralysis. The underlying science governing neuromusculoskeletal adaptations after paralysis will help guide professionals as new rehabilitation strategies evolve in the future.
Moxon, Karen A.; Oliviero, Antonio; Aguilar, Juan; Foffani, Guglielmo
Plasticity constitutes the basis of behavioral changes as a result of experience. It refers to neural network shaping and re-shaping at the global level and to synaptic contacts remodeling at the local level, either during learning or memory encoding, or as a result of acute or chronic pathological conditions. ‘Plastic’ brain reorganization after central nervous system lesions has a pivotal role in the recovery and rehabilitation of sensory and motor dysfunction, but can also be “maladaptive”. Moreover, it is clear that brain reorganization it is not a “static” phenomenon but rather a very dynamic process. Spinal cord injury immediately initiates a change in brain state and starts cortical reorganization. In the long term, the impact of injury – with or without accompanying therapy – on the brain is a complex balance between supraspinal reorganization and spinal recovery. The degree of cortical reorganization after spinal cord injury is highly variable, and can range from no reorganization (i.e. “silencing”) to massive cortical remapping. This variability critically depends on the species, the age of the animal when the injury occurs, the time after the injury has occurred, and the behavioral activity and possible therapy regimes after the injury. We will briefly discuss these dependencies, trying to highlight their translational value. Overall, it is not only necessary to better understand how the brain can reorganize after injury with or without therapy, it is also necessary to clarify when and why brain reorganization can be either “good” or “bad” in terms of its clinical consequences. This information is critical in order to develop and optimize cost-effective therapies to maximize functional recovery while minimizing maladaptive states after spinal cord injury. PMID:24997269
Humanes-Valera, Desiré; Alonso-Calviño, Elena; Yague, Josué G.; Moxon, Karen A.; Oliviero, Antonio
Spinal cord injury can produce extensive long-term reorganization of the cerebral cortex. Little is known, however, about the sequence of cortical events starting immediately after the lesion. Here we show that a complete thoracic transection of the spinal cord produces immediate functional reorganization in the primary somatosensory cortex of anesthetized rats. Besides the obvious loss of cortical responses to hindpaw stimuli (below the level of the lesion), cortical responses evoked by forepaw stimuli (above the level of the lesion) markedly increase. Importantly, these increased responses correlate with a slower and overall more silent cortical spontaneous activity, representing a switch to a network state of slow-wave activity similar to that observed during slow-wave sleep. The same immediate cortical changes are observed after reversible pharmacological block of spinal cord conduction, but not after sham. We conclude that the deafferentation due to spinal cord injury can immediately (within minutes) change the state of large cortical networks, and that this state change plays a critical role in the early cortical reorganization after spinal cord injury. PMID:20519527
Denervation of the spinal cord below the level of injury leads to complications producing malnutrition. Nutritional status affects mortality and pathology of injured subjects and it has been reported that two thirds of individuals enrolled in rehabilitation units are malnourished. Therefore, the aim should be either to maintain an optimal nutritional status, or supplement these subjects in order to overcome deficiencies in nutrients or prevent obesity. This paper reviews methods of nutritional assessment and describes the physiopathological mechanisms of malnutrition based on the assumption that spinal cord injured subjects need to receive adequate nutrition to promote optimal recovery, placing nutrition as a first line treatment and not an afterthought in the rehabilitation of spinal cord injury. PMID:22870169
Hoh, Daniel J.; Mercier, Lynne M.; Hussey, Shaunn P.; Lane, Michael A.
Respiratory dysfunction is one of the most devastating consequences of cervical spinal cord injury (SCI) with impaired breathing being a leading cause of morbidity and mortality in this population. However, there is mounting experimental and clinical evidence for moderate spontaneous respiratory recovery, or “plasticity”, after some spinal cord injuries. Pre-clinical models of respiratory dysfunction following SCI have demonstrated plasticity at neural and behavioral levels that result in progressive recovery of function. Temporal changes in respiration after human SCI have revealed some functional improvements suggesting plasticity paralleling that seen in experimental models – a concept that has been previously under-appreciated. While the extent of spontaneous recovery remains limited, it is possible that enhancing or facilitating neuroplastic mechanisms may have significant therapeutic potential. The next generation of treatment strategies for SCI and related respiratory dysfunction should aim to optimize these recovery processes of the injured spinal cord for lasting functional restoration. PMID:23891679
Duan, Hongmei; Song, Wei; Zhao, Wen; Gao, Yudan; Yang, Zhaoyang; Li, Xiaoguang
During the whole life cycle of mammals, new neurons are constantly regenerated in the subgranular zone of the dentate gyrus and in the subventricular zone of the lateral ventricles. Thanks to emerging methodologies, great progress has been made in the characterization of spinal cord endogenous neural stem cells (ependymal cells) and identification of their role in adult spinal cord development. As recently evidenced, both the intrinsic and extrinsic molecular mechanisms of ependymal cells control the sequential steps of the adult spinal cord neurogenesis. This review introduces the concept of adult endogenous neurogenesis, the reaction of ependymal cells after adult spinal cord injury (SCI), the heterogeneity and markers of ependymal cells, the factors that regulate ependymal cells, and the niches that impact the activation or differentiation of ependymal cells.
He, Zili; Zou, Shuang; Wang, Qingqing; Li, Jiawei; Zheng, Zengming; Chen, Jian; Wu, Fenzan; Gong, Fanhua; Zhang, Hongyu; Xu, Huazi; Xiao, Jian
Spinal cord injury induces the disruption of blood-spinal cord barrier and triggers a complex array of tissue responses, including endoplasmic reticulum (ER) stress and autophagy. However, the roles of ER stress and autophagy in blood-spinal cord barrier disruption have not been discussed in acute spinal cord trauma. In the present study, we respectively detected the roles of ER stress and autophagy in blood-spinal cord barrier disruption after spinal cord injury. Besides, we also detected the cross-talking between autophagy and ER stress both in vivo and in vitro. ER stress inhibitor, 4-phenylbutyric acid, and autophagy inhibitor, chloroquine, were respectively or combinedly administrated in the model of acute spinal cord injury rats. At day 1 after spinal cord injury, blood-spinal cord barrier was disrupted and activation of ER stress and autophagy were involved in the rat model of trauma. Inhibition of ER stress by treating with 4-phenylbutyric acid decreased blood-spinal cord barrier permeability, prevented the loss of tight junction (TJ) proteins and reduced autophagy activation after spinal cord injury. On the contrary, inhibition of autophagy by treating with chloroquine exacerbated blood-spinal cord barrier permeability, promoted the loss of TJ proteins and enhanced ER stress after spinal cord injury. When 4-phenylbutyric acid and chloroquine were combinedly administrated in spinal cord injury rats, chloroquine abolished the blood-spinal cord barrier protective effect of 4-phenylbutyric acid by exacerbating ER stress after spinal cord injury, indicating that the cross-talking between autophagy and ER stress may play a central role on blood-spinal cord barrier integrity in acute spinal cord injury. The present study illustrates that ER stress induced by spinal cord injury plays a detrimental role on blood-spinal cord barrier integrity, on the contrary, autophagy induced by spinal cord injury plays a furthersome role in blood-spinal cord barrier integrity in
Zhou, Yulong; Wu, Yanqing; Liu, Yanlong; He, Zili; Zou, Shuang; Wang, Qingqing; Li, Jiawei; Zheng, Zengming; Chen, Jian; Wu, Fenzan; Gong, Fanhua; Zhang, Hongyu; Xu, Huazi; Xiao, Jian
Spinal cord injury induces the disruption of blood-spinal cord barrier and triggers a complex array of tissue responses, including endoplasmic reticulum (ER) stress and autophagy. However, the roles of ER stress and autophagy in blood-spinal cord barrier disruption have not been discussed in acute spinal cord trauma. In the present study, we respectively detected the roles of ER stress and autophagy in blood-spinal cord barrier disruption after spinal cord injury. Besides, we also detected the cross-talking between autophagy and ER stress both in vivo and in vitro. ER stress inhibitor, 4-phenylbutyric acid, and autophagy inhibitor, chloroquine, were respectively or combinedly administrated in the model of acute spinal cord injury rats. At day 1 after spinal cord injury, blood-spinal cord barrier was disrupted and activation of ER stress and autophagy were involved in the rat model of trauma. Inhibition of ER stress by treating with 4-phenylbutyric acid decreased blood-spinal cord barrier permeability, prevented the loss of tight junction (TJ) proteins and reduced autophagy activation after spinal cord injury. On the contrary, inhibition of autophagy by treating with chloroquine exacerbated blood-spinal cord barrier permeability, promoted the loss of TJ proteins and enhanced ER stress after spinal cord injury. When 4-phenylbutyric acid and chloroquine were combinedly administrated in spinal cord injury rats, chloroquine abolished the blood-spinal cord barrier protective effect of 4-phenylbutyric acid by exacerbating ER stress after spinal cord injury, indicating that the cross-talking between autophagy and ER stress may play a central role on blood-spinal cord barrier integrity in acute spinal cord injury. The present study illustrates that ER stress induced by spinal cord injury plays a detrimental role on blood-spinal cord barrier integrity, on the contrary, autophagy induced by spinal cord injury plays a furthersome role in blood-spinal cord barrier integrity in
Dworkin, Gerald M.
Water-related activities are the number one cause of spinal cord injuries resulting from sports and recreation activities. This article discusses principles of safe diving; principles of safe water sliding; ways to reduce springboard diving accidents; factors contributing to springboard diving accidents; and safety recommendations for open water…
Heinemann, Allen W.; And Others
Substance use histories were obtained from 103 persons (16 to 63 years of age) with recent spinal cord injuries (SCI). Lifetime exposure to and current use of substances with abuse potential were substantially greater in this sample compared to a like-age national sample. Exposure to and recent use of substances with abuse potential was…
Gurcay, Eda; Bal, Ajda; Eksioglu, Emel; Cakci, Aytul
The primary objective of this study was to assess the quality of life (QoL) in spinal cord injury (SCI) survivors. Secondary objectives were to determine the effects of various sociodemographic and clinical characteristics on QoL. This cross-sectional study included 54 patients with SCI. The Turkish version of the Short-Form-36 Health Survey was…
Yuksel, Kasım Zafer
Study Design Retrospective review. Purpose We retrospectively reviewed our patients with ankylosing spondylitis (AS) to identify their patterns of spinal fractures to help clarify management strategies and the morbidity and mortality rates associated with this group of patients. Overview of Literature Because of the brittleness of bone and long autofused spinal segments in AS, spinal fractures are common even after minor trauma and often associated with overt instability. Methods Between January 1, 1998 and March 2011, 30 patients (23 males, 7 females; mean age, 70.43 years; range, 45 to 95 years) with the radiographic diagnosis of AS of the spinal column had 42 fractures. Eight patients presented with significant trauma, 17 after falls, and 5 after minor falls or no recorded trauma. Eleven patients presented with a neurological injury, ranging from mild sensory loss to quadriplegia. Results There were 16 compression and 10 transverse fractures, two Jefferson's fractures, one type II and two type III odontoid process fractures, and five fractures of the posterior spinal elements (including lamina and/or facet, three spinous process fractures, three transverse process fractures). Twenty-four fractures affected the craniocervical junction and/or cervical vertebrae, 17 were thoracic, and one involved the lumbar spine. The most affected vertebrae were C6 and T10. The mean follow-up was 29.9 months. One patient was lost to follow-up. Eighteen patients were treated conservatively with bed rest and bracing. Twelve patients underwent surgery for spinal stabilization either with an anterior, posterior or combined approach. Conclusions Nonsurgical treatment can be considered especially in the elderly patients with AS and spinal trauma but without instability or major neurological deficits. The nonfusion rate in conservatively treated patients is low. When treatment is selected for patients with spinal fractures and AS, the pattern of injury must be considered and the need
Taylor, T K; Coolican, M R
A review of 107 footballers who suffered a spinal-cord injury between 1960 and 1985 has been undertaken. Since 1977, the number of such injuries in Rugby Union, Rugby League and Australian Rules has increased, from an average of about two injuries a year before 1977 to over eight injuries a year since then. Rugby Union is clearly the most dangerous game, particularly for schoolboys; all of the injuries in schoolboy games for this code have occurred since 1977. This study has shown that collision at scrum engagement, and not at scrum collapse, is the way in which the majority of scrum injuries are sustained. These injuries are largely preventable, and suggestions for rule changes are made. Half the injured players recovered to Frankel grades D or E. The financial entitlements of those injured were grossly inadequate; this warrants action. A national register for spinal-cord injuries from football should be established to monitor the effects of desirable rule changes in Rugby Union and Rugby League.
Wadsworth, Brooke; Ross, Jack
Spinal cord injury (SCI) is characterised by profound respiratory compromise secondary to the level of loss of motor, sensory and autonomic control associated with the injury. This review aims to detail these anatomical and physiological changes after SCI, and outline their impact on respiratory function. Injury-related impairments in strength substantially alter pulmonary mechanics, which in turn affect respiratory management and care. Options for treatments must therefore be considered in light of these limitations. Key points Respiratory impairment following spinal cord injury (SCI) is more severe in high cervical injuries, and is characterised by low lung volumes and a weak cough secondary to respiratory muscle weakness. Autonomic dysfunction and early-onset sleep disordered breathing compound this respiratory compromise. The mainstays of management following acute high cervical SCI are tracheostomy and ventilation, with noninvasive ventilation and assisted coughing techniques being important in lower cervical and thoracic level injuries. Prompt investigation to ascertain the extent of the SCI and associated injuries, and appropriate subsequent management are important to improve outcomes. Educational aims To describe the anatomical and physiological changes after SCI and their impact on respiratory function. To describe the changes in respiratory mechanics seen in cervical SCI and how these changes affect treatments. To discuss the relationship between injury level and respiratory compromise following SCI, and describe those at increased risk of respiratory complications. To present the current treatment options available and their supporting evidence. PMID:28270863
Hou, Shaoping; Carson, David M; Wu, Di; Klaw, Michelle C; Houlé, John D; Tom, Veronica J
Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH)(+) neurons in the autonomic nuclei and superficial dorsal horn in L6-S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH)(-) and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH(+) neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D2-like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH(+) neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH(+) cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH(+) neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI.
Mathew, Bruce; Laden, Gerard
There is an increasing body of evidence that drainage of lumbar cerebrospinal fluid (CSF) improves functional neurological outcome after reperfusion injury to the spinal cord that occasionally follows aortic reconstructive surgery. This beneficial effect is considered owing to lowering of the CSF pressure thereby normalising spinal cord blood flow and reducing the 'secondary' cord injury caused by vascular congestion and cord swelling in the relatively confined spinal canal. Whilst lacking definitive proof, there are convincing randomised controlled trials (RCTs), cohort data and systematic reviews supporting this intervention. The therapeutic window for lumbar CSF drainage requires further elucidation; however, it appears to be days rather than hours post insult. We contend that the same benefit is likely to be achieved following other primary spinal cord injuries that cause cord swelling and elicit the 'secondary' injury. Traditionally the concept of CSF drainage has been considered more applicable to the brain as contained in a 'closed box' by lowering intracranial pressure (ICP) to improve cerebral perfusion pressure (CPP). The control of CPP is intended to limit 'secondary' brain injury and is a key concept of brain injury management. Using microdialysis in the spinal cords of trauma patients, it has been shown that intraspinal pressure (ISP) needs to be kept below 20 mmHg and spinal cord perfusion pressure (SCPP) above 70 mmHg to avoid biochemical evidence of secondary cord damage. Vasopressor have also been used in spinal cord injury to improve perfusion, however complications are common, typically cardiac in nature, and require very careful monitoring; the evidence supporting this approach is notably less convincing. Decompression illness (DCI) of the spinal cord is treated with recompression, hyperbaric oxygen, various medications designed to reduce the inflammatory response and fluid administration to normalise blood pressure and haematocrit. These
Louisville, KY After spinal cord injury (SCI) patients commonly develop spasticity and contractures as secondary complications of “upper motor neuron...lesions. Physical therapists use stretching maneuvers to maintain extensibility of soft tissues and to manage spasticity . Previous studies in our lab
Taghva, Alexander; Hoh, Daniel J; Lauryssen, Carl L
Spinal cord injury (SCI) is a significant public problem, with recent data suggesting that over 1 million people in the U.S.A. alone are affected by paralysis resulting from SCI. Recent advances in prehospital care have improved survival as well as reduced incidence and severity of SCI following spine trauma. Furthermore, increased understanding of the secondary mechanisms of injury following SCI has provided improvements in critical care and acute management in patients suffering from SCI, thus limiting morbidity following injury. In addition, improved technology and biomechanical understanding of the mechanisms of spine trauma have allowed further advances in available techniques for spinal decompression and stabilization. In this chapter we review the most recent data and salient literature regarding SCI and address current controversies, including the use of pharmacological adjuncts in the setting of acute SCI. We will also attempt to provide a reader with basic understanding of the classifications of SCI and spinal column injury. Finally, we review advances in spinal column stabilization including improvements in instrumented fusion and minimally invasive surgery.
Leskovar, A; Turek, J; Borgens, R B
Using a cell-isolation and -culture procedure specific for macrophages, we report the existence of giant (more than 50 microm diameter), multinucleated macrophages within an acute, 5-day-old adult rat spinal cord injury. The size and multinuclearity of these isolated giant cells was confirmed using transmission electron microscopy. Giant macrophages are markers for long-term infection, disease, and chronic injury in other soft tissues and are unexpected in the acute inflammatory stage of central nervous system injury. To our knowledge, this descriptive report is the first confirming the existence of giant macrophages in any injured nervous tissue, with additional data suggesting some of these cells to be multinucleated.
DeVivo, M J; Kartus, P L; Stover, S L; Rutt, R D; Fine, P R
An epidemiologic study of 5131 patients sustaining spinal cord injuries between 1973 and 1980 was conducted to determine and characterize the leading causes of death in this population. Patients who were studied had been admitted to one of seven federally designated regional spinal cord injury care systems and they survived for at least 24 hours after injury. When follow-up was terminated, 459 patients (9%) had died. Overall, the leading cause of death was pneumonia, followed by other subsequent unintentional injuries and suicides. The highest ratios of actual to expected deaths were for septicemia, pulmonary emboli, and pneumonia. Pneumonia was the leading cause of death among quadriplegics and persons at least 55 years of age, while among paraplegics and persons who were less than 55 years of age, subsequent unintentional injuries and suicides were the leading causes of death. While there is conclusive evidence that mortality rates for spinal-cord injured persons have declined dramatically since the end of World War II, many cause-specific mortality rates remain substantially above normal.
Kim, David H; Vaccaro, Alexander R; Berta, Scott C
Improvements in helmet and equipment design have led to significant decreases in overall injury incidence, but no available helmet can prevent catastrophic injury to the neck and cervical spine. The most effective strategy for preventing this type of injury appears to be careful instruction, training, and regulations designed to eliminate head-first contact. The incidence of football-related quadriplegia has decreased from a peak of 13 cases per one million players between 1976 and 1980 to 3 per million from 1991 to 1993, mostly as a result of systematic research and an organized effort to eliminate high-risk behavior. An episode of transient quadriparesis does not appear to be a risk factor for catastrophic spinal cord injury. Torg reported that 0 of 117 quadriplegics in the National Football Head and Neck Injuries Registry recalled a prior episode of transient quadriparesis, and 0 of the 45 patients originally studied in his transient quadriparesis cohort have subsequently suffered quadriplegia. The significance of developmental spinal stenosis is unclear. Plain radiographic identification of a narrow spinal canal in a player sustaining cervical cord neurapraxia warrants further evaluation by MRI to rule out functional stenosis. The presence of actual cord deformation or compression on MRI should preclude participation in high-risk contact or collision sports.
elicits a number of changes in the activity, properties and transmitter content of pain -pathway neurons2. This central sensitization to nociceptive ...AD______ Award Number: W81XHW-11-1-0806 TITLE: Chronic pain following spinal cord injury. The...role of immunogenetics and time of injury pain treatment. PRINCIPAL INVESTIGATOR: Dr. Mark Hutchinson CONTRACTING ORGANIZATION: The
Pollard, Henry; Fernandez, Matt
Objectives: To review the biomechanics of the swimming stroke and examine common injuries which occur in swimming. A review of diagnosis and management strategies of these injuries is also performed. Background: Most injuries and complaints encountered in swimming athletes occur because of repetitive microtrauma or overuse, with many injuries originating from faulty technique and poor swimming biomechanics. As a result, assessment of an injured athlete requires the practitioner to have an understanding of the four swimming strokes and hydrodynamics. Methods: A Literature search of the MEDLINE and MANTIS databases was performed on all swimming related articles. Results: Twenty seven journal articles and 7 text books were chosen that satisfied the search criteria and related to the aims of this review. Discussion: The correct swimming technique is discussed and predisposing factors to injury in the stroke are identified. Specific injury sites are examined and pathologies to these areas are detailed. Conclusion: The shoulder, neck and back are the injuries considered in this review. These regions are considered in the total training program of the athlete to identify other factors, such as weight training or other dry land programs that may be contributing to injury. However, whilst rest or reduced training may be necessary for recovery, every effort must be made to keep the swimmer “in the water” as cessation of training may lead to a rapid detraining effect and loss of competitive advantage. PMID:17987215
Steward, Oswald; Willenberg, Rafer
For over a century, axon regeneration has been considered the Holy Grail for spinal cord injury (SCI) repair. Although there are other factors that could contribute to improving function, restoring the long motor and sensory tracts that are interrupted by SCI has the greatest potential for actually reversing paralysis, restoring the brain's control of autonomic functions mediated by sympathetic and parasympathetic circuits of the spinal cord and restoring sensation. Accordingly and in keeping with the overall theme of this special issue, this review focuses narrowly on rodent SCI models for studies of axon regeneration.
Reintegration of Service-Members and Veterans with Spinal Cord Injury PRINCIPAL INVESTIGATOR: Seth D. Messinger...SUBTITLE Developing a Meaningful Life: Social Reintegration of Service- Social Reintegration of Service Me Members and Veterans with Spinal Cord...communities and cultural identities that is key to long-term success . 15. SUBJECT TERMS Spinal Cord Injury, Community Reintegration , Qualitative
... AFFAIRS Agency Information Collection (Spinal Cord Injury Patient Care Survey) Under OMB Review AGENCY.... 2900-New (VA Form 10-0515).'' SUPPLEMENTARY INFORMATION: Title: Spinal Cord Injury Patient Care Survey... Collection. Abstract: Information collected on VA Form 10-0515 will be used to determine spinal cord...
Zhang, Guanghao; Huo, Xiaolin; Wang, Aihua; Wu, Changzhe; Zhang, Cheng; Bai, Jinzhu
An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This injury potential, as well as injury current, can be modulated by direct current field stimulation; however, the appropriate parameters of the electrical field are hard to define. In this paper, injury potential is used as a parameter to adjust the intensity of electrical stimulation. Injury potential could be modulated to slightly above 0 mV (as the anode-centered group) by placing the anodes at the site of the injured spinal cord and the cathodes at the rostral and caudal sections, or around –70 mV, which is resting membrane potential (as the cathode-centered group) by reversing the polarity of electrodes in the anode-centered group. In addition, rats receiving no electrical stimulation were used as the control group. Results showed that the absolute value of the injury potentials acquired after 30 minutes of electrical stimulation was higher than the control group rats and much lower than the initial absolute value, whether the anodes or the cathodes were placed at the site of injury. This phenomenon illustrates that by changing the polarity of the electrical field, electrical stimulation can effectively modulate the injury potentials in rats after spinal cord injury. This is also beneficial for the spontaneous repair of the cell membrane and the reduction of cation influx. PMID:25206563
Macedonia, Christian; Zamisch, Monica; Judy, Jack; Ling, Geoffrey
The repair of traumatic injuries to the central nervous system remains among the most challenging and exciting frontiers in medicine. In both traumatic brain injury and spinal cord injuries, the ultimate goals are to minimize damage and foster recovery. Numerous DARPA initiatives are in progress to meet these goals. The PREventing Violent Explosive Neurologic Trauma program focuses on the characterization of non-penetrating brain injuries resulting from explosive blast, devising predictive models and test platforms, and creating strategies for mitigation and treatment. To this end, animal models of blast induced brain injury are being established, including swine and non-human primates. Assessment of brain injury in blast injured humans will provide invaluable information on brain injury associated motor and cognitive dysfunctions. The Blast Gauge effort provided a device to measure warfighter's blast exposures which will contribute to diagnosing the level of brain injury. The program Cavitation as a Damage Mechanism for Traumatic Brain Injury from Explosive Blast developed mathematical models that predict stresses, strains, and cavitation induced from blast exposures, and is devising mitigation technologies to eliminate injuries resulting from cavitation. The Revolutionizing Prosthetics program is developing an avant-garde prosthetic arm that responds to direct neural control and provides sensory feedback through electrical stimulation. The Reliable Neural-Interface Technology effort will devise technologies to optimally extract information from the nervous system to control next generation prosthetic devices with high fidelity. The emerging knowledge and technologies arising from these DARPA programs will significantly improve the treatment of brain and spinal cord injured patients.
van Middendorp, Joost J.; Goss, Ben; Urquhart, Susan; Atresh, Sridhar; Williams, Richard P.; Schuetz, Michael
Despite promising advances in basic spinal cord repair research, no effective therapy resulting in major neurological or functional recovery after traumatic spinal cord injury (tSCI) is available to date. The neurological examination according to the International Standards for Neurological and Functional Classification of Spinal Cord Injury Patients (International Standards) has become the cornerstone in the assessment of the severity and level of the injury. Based on parameters from the International Standards, physicians are able to inform patients about the predicted long-term outcomes, including the ability to walk, with high accuracy. In those patients who cannot participate in a reliable physical neurological examination, magnetic resonance imaging and electrophysiological examinations may provide useful diagnostic and prognostic information. As clinical research on this topic continues, the prognostic value of the reviewed diagnostic assessments will become more accurate in the near future. These advances will provide useful information for physicians to counsel tSCI patients and their families during the catastrophic initial phase after the injury. PMID:24353930
Vierck, Charles J; Cannon, Richard L; Acosta-Rua, Antonio J
Operant escape from nociceptive thermal stimulation of 13 Long-Evans rats was compared before and after lateral spinal hemisection, to determine whether this lesion configuration provides an appropriate preclinical model of the hyperalgesia that can be associated with human spinal cord injury. Escape from 44 °C and from 47 °C stimulation was not affected following sham spinal surgery but was significantly reduced over 20 weeks of postoperative testing following lateral spinal hemisection. This result is opposite to previous reports of enhanced reflex withdrawal in response to thermal stimulation of rats following lateral spinal hemisection. In addition, the latency of reflexive lick/guard responses to 44 °C was increased and the duration of lick/guard responding was decreased in the present study (hyporeflexia). Thus, previous assessments of simple withdrawal reflexes have described a hyperreflexia following lateral spinal hemisection that was not replicated by lick/guard testing, and postoperative escape responding revealed hypoalgesia rather than the increased pain sensitivity expected in a model of chronic pain.
Fu, Juanjuan; Deng, Lingxiao; Li, Jianan
The exercise training is an effective therapy for spinal cord injury which has been applied to clinic. Traditionally, the exercise training has been considered to improve spinal cord function only through enhancement, compensation, and replacement of the remaining function of nerve and muscle. Recently, accumulating evidences indicated that exercise training can improve the function in different levels from end-effector organ such as skeletal muscle to cerebral cortex through reshaping skeletal muscle structure and muscle fiber type, regulating physiological and metabolic function of motor neurons in the spinal cord and remodeling function of the cerebral cortex. We compiled published data collected in different animal models and clinical studies into a succinct review of the current state of knowledge. PMID:28050288
Smith, AC; Parrish, TB; Hoggarth, MA; McPherson, JG; Tysseling, VM; Wasielewski, M; Kim, HE; Hornby, TG; Elliott, JM
Study Design: This research utilized a cross-sectional design with control group inclusion. Objectives: Preliminary evidence suggests that a portion of the patient population with chronic whiplash may have sustained spinal cord damage. Our hypothesis is that in some cases of chronic whiplash-associated disorders (WAD), observed muscle weakness in the legs will be associated with local signs of a partial spinal cord injury of the cervical spine. Setting: University based laboratory in Chicago, IL, USA. Methods: Five participants with chronic WAD were compared with five gender/age/height/weight/body mass index (BMI) control participants. For a secondary investigation, the chronic WAD group was compared with five unmatched participants with motor incomplete spinal cord injury (iSCI). Spinal cord motor tract integrity was assessed using magnetization transfer imaging. Muscle fat infiltration (MFI) was quantified using fat/water separation magnetic resonance imaging. Central volitional muscle activation of the plantarflexors was assessed using a burst superimposition technique. Results: We found reduced spinal cord motor tract integrity, increased MFI of the neck and lower extremity muscles and significantly impaired voluntary plantarflexor muscle activation in five participants with chronic WAD. The lower extremity structural changes and volitional weakness in chronic WAD were comparable to participants with iSCI. Conclusion: The results support the position that a subset of the chronic whiplash population may have sustained partial damage to the spinal cord. Sponsorship: NIH R01HD079076-01A1, NIH T32 HD057845 and the Foundation for Physical Therapy Promotion of Doctoral Studies program. PMID:27630770
Züchner, Mark; Glover, Joel C.; Boulland, Jean-Luc
Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal cord. A major current area of research is focused on the mechanisms of adaptive plasticity that underlie spontaneous or induced functional recovery following SCI. Spontaneous functional recovery is reported to be greater early in life, raising interesting questions about how adaptive plasticity changes as the spinal cord develops. To facilitate investigation of this dynamic, we have developed a SCI model in the neonatal mouse. The model has relevance for pediatric SCI, which is too little studied. Because neural plasticity in the adult involves some of the same mechanisms as neural plasticity in early life1, this model may potentially have some relevance also for adult SCI. Here we describe the entire procedure for generating a reproducible spinal cord compression (SCC) injury in the neonatal mouse as early as postnatal (P) day 1. SCC is achieved by performing a laminectomy at a given spinal level (here described at thoracic levels 9-11) and then using a modified Yasargil aneurysm mini-clip to rapidly compress and decompress the spinal cord. As previously described, the injured neonatal mice can be tested for behavioral deficits or sacrificed for ex vivo physiological analysis of synaptic connectivity using electrophysiological and high-throughput optical recording techniques1. Earlier and ongoing studies using behavioral and physiological assessment have demonstrated a dramatic, acute impairment of hindlimb motility followed by a complete functional recovery within 2 weeks, and the first evidence of changes in functional circuitry at the level of identified descending synaptic connections1. PMID:27078037
Ross, Christina L; Syed, Ishaq; Smith, Thomas L; Harrison, Benjamin S
Traumatic spinal cord injury (SCI) is typically the result of direct mechanical impact to the spine, leading to fracture and/or dislocation of the vertebrae along with damage to the surrounding soft tissues. Injury to the spinal cord results in disruption of axonal transmission of signals. This primary trauma causes secondary injuries that produce immunological responses such as neuroinflammation, which perpetuates neurodegeneration and cytotoxicity within the injured spinal cord. To date there is no FDA-approved pharmacological agent to prevent the development of secondary SCI and induce regenerative processes aimed at healing the spinal cord and restoring neurological function. An alternative method to electrically activate spinal circuits is the application of a noninvasive electromagnetic field (EMF) over intact vertebrae. The EMF method of modulating molecular signaling of inflammatory cells emitted in the extra-low frequency range of <100 Hz, and field strengths of <5 mT, has been reported to decrease inflammatory markers in macrophages, and increase endogenous mesenchymal stem cell (MSC) proliferation and differentiation rates. EMF has been reported to promote osteogenesis by improving the effects of osteogenic media, and increasing the proliferation of osteoblasts, while inhibiting osteoclast formation and increasing bone matrix in vitro. EMF has also been shown to increase chondrogenic markers and collagen and induce neural differentiation, while increasing cell viability by over 50%. As advances are made in stem cell technologies, stabilizing the cell line after differentiation is crucial to SCI repair. Once cell-seeded scaffolds are implanted, EMF may be applied outside the wound for potential continued adjunct treatment during recovery.
1 sheds light on the dynamic changes that occur with oxygenation , blood flow, and metabolic responses in the penumbra of the traumatic spinal cord...critical reduction of substrate (glucose/ oxygen ) delivery. Following decompression only partially recovery was observed for blood flow, oxygen and glucose...and persisted for several hours. Distal to the injury we also observed a decrease in spinal cord oxygenation although more progressive over time
Noonan, Vanessa K; Thorogood, Nancy P; Fingas, Matthew; Batke, Juliet; Bélanger, Lise; Kwon, Brian K; Dvorak, Marcel F
International Classification of Diseases (ICD) codes are used to document patient morbidity in administrative databases. Although administrative data are used for research purposes, the validity of the data to accurately describe clinical diagnostic information is uncertain. We compared the clinical diagnoses for spinal cord and column injuries from a longitudinal patient registry, the Rick Hansen Spinal Cord Injury Registry (RHSCIR), to the ICD-10 spinal injury codes from the Discharge Abstract Database (DAD) at one institution. There were 603 RHSCIR participants with data describing the spinal cord injury, and 341 had data on the spinal column injury. The validity of DAD data to describe spinal injuries was evaluated using the sensitivity and positive predictive values of specific ICD-10 codes; 5.3% of the spinal column injuries and 10.9% of the spinal cord injuries documented in RHSCIR were missed in data from the DAD using ICD-10 codes. The most problematic spinal column ICD-10 code was the dislocation of the cervical vertebra (S13.1); only 14.0% of the dislocations of the cervical vertebrae in RHSCIR were correctly coded in the DAD. The most problematic spinal cord injury ICD-10 code was the incomplete lesion of the lumbar spinal cord (S34.1X); 66.7% of incomplete lesions of the lumbar spinal cord in RHSCIR were correctly coded in the DAD. The validity of DAD data to code spinal injuries is variable, and cannot be reliably used to classify all types of spinal injuries. Patient registries, such as RHSCIR, should be used if accurate detailed diagnostic data are required.
... AFFAIRS Proposed Information Collection (Spinal Cord Injury Patient Care Survey) Activity: Comment Request... spinal cord patients' satisfaction with VA rehabilitation and health care system. Affected Public... of automated collection techniques or the use of other forms of information technology. Title:...
Hawthorne, Alicia L; Popovich, Phillip G
Traumatic spinal cord injury (SCI) affects the activation, migration, and function of microglia, neutrophils and monocyte/macrophages. Because these myeloid cells can positively and negatively affect survival of neurons and glia, they are among the most commonly studied immune cells. However, the mechanisms that regulate myeloid cell activation and recruitment after SCI have not been adequately defined. In general, the dynamics and composition of myeloid cell recruitment to the injured spinal cord are consistent between mammalian species; only the onset, duration, and magnitude of the response vary. Emerging data, mostly from rat and mouse SCI models, indicate that resident and recruited myeloid cells are derived from multiple sources, including the yolk sac during development and the bone marrow and spleen in adulthood. After SCI, a complex array of chemokines and cytokines regulate myelopoiesis and intraspinal trafficking of myeloid cells. As these cells accumulate in the injured spinal cord, the collective actions of diverse cues in the lesion environment help to create an inflammatory response marked by tremendous phenotypic and functional heterogeneity. Indeed, it is difficult to attribute specific reparative or injurious functions to one or more myeloid cells because of convergence of cell function and difficulties in using specific molecular markers to distinguish between subsets of myeloid cell populations. Here we review each of these concepts and include a discussion of future challenges that will need to be overcome to develop newer and improved immune modulatory therapies for the injured brain or spinal cord.
Tian, Mei; Zhang, Hong
Spinal cord injury (SCI) is a serious disease of the center nervous system (CNS). It is a devastating injury with sudden loss of motor, sensory, and autonomic function distal to the level of trauma and produces great personal and societal costs. Currently, there are no remarkable effective therapies for the treatment of SCI. Compared to traditional treatment methods, stem cell transplantation therapy holds potential for repair and functional plasticity after SCI. However, the mechanism of stem cell therapy for SCI remains largely unknown and obscure partly due to the lack of efficient stem cell trafficking methods. Molecular imaging technology including positron emission tomography (PET), magnetic resonance imaging (MRI), optical imaging (i.e., bioluminescence imaging (BLI)) gives the hope to complete the knowledge concerning basic stem cell biology survival, migration, differentiation, and integration in real time when transplanted into damaged spinal cord. In this paper, we mainly review the molecular imaging technology in stem cell therapy for SCI. PMID:24701583
Scher, A T
In reports from the UK and New Zealand, it is noted that the incidence of rugby injuries to the cervical spinal cord has dropped and that the percentage of players injured in the tackle has similarly decreased. In contrast, this does not appear to be the pattern in South Africa and an analysis has therefore been made of 40 rugby players sustaining injuries to the spinal cord during the period 1985 to 1989. The radiological appearances on admission have been correlated with the circumstances of injury, associated orthopaedic injuries and neurological deficits. The tackle was responsible for the majority of injuries, causing more than the scrum. Tackles were also responsible for more cases of complete, permanent quadriplegia than the scrum. The commonest cause of injury in players being tackled was the high tackle around the neck, while the commonest cause of injury in players making the tackle was the dive tackle. This survey has shown that the tackle is now the major cause of spinal cord injury in South African rugby, in contrast to earlier analyses in which the scrum was identified as the most common cause.
Donnelly, Catherine; Eng, Janice J
Study Design Prospective, correlational Objectives 1) describe how pain changes over recovery from admission to spinal cord injury (SCI) rehabilitation, discharge and after 6 months of community living and 2) examine the relationship between pain and community integration at 6 months of community living. Setting Tertiary rehabilitation centre, spinal cord injury unit, Vancouver, Canada. Methods Subjects from 66 consecutive admissions to the Spinal Cord Injury Program of a tertiary rehabilitation centre for the treatment of a traumatic spinal cord injury during the years 2000 to 2002 were followed using data from the National Rehabilitation Reporting System (NRRS). Information was obtained from NRRS standardized assessments performed on admission, discharge and 6 month community living. Early community living was defined as 6-months post-discharge. Community re-integration was assessed by the Reintegration to Normal Living Index (RNL). Pain presence, pain impact and pain intensity were assessed using single item Likhert type scales. Results 86% of individuals with a SCI reported pain at 6-months post discharge, with 27% of these individuals reporting pain that impacted on many or most activities. Pain impact and pain intensity were related to the community re-integration (r=−0.39 and r=−0.55, p<.001), with pain intensity accounting for 25% of the variance in RNL scores. Conclusions Pain is a major consequence of a SCI, impacting on an individual’s activities and perception of how well they are integrated into the community. The results of this study highlight the need to address pain during both the rehabilitation phase of treatment and the early transition into the community. PMID:15570317
Infertility in individuals with neurologic disorders is complex in etiology and manifestation. Its management therefore often requires a multimodal approach. This review addresses the implications of spinal cord injury (SCI) and other neurologic disease on fertility, including the high prevalence of sexual dysfunction, ejaculation disorders and compromised semen parameters. Available treatment approaches discussed include assisted ejaculation techniques and assisted reproductive technology including surgical sperm retrieval and intracytoplasmic sperm injection (ICSI). PMID:26904416
Trofimenko, Vera; Hotaling, James M
Infertility in individuals with neurologic disorders is complex in etiology and manifestation. Its management therefore often requires a multimodal approach. This review addresses the implications of spinal cord injury (SCI) and other neurologic disease on fertility, including the high prevalence of sexual dysfunction, ejaculation disorders and compromised semen parameters. Available treatment approaches discussed include assisted ejaculation techniques and assisted reproductive technology including surgical sperm retrieval and intracytoplasmic sperm injection (ICSI).
Hachmann, Jan T.; Calvert, Jonathan S.; Grahn, Peter J.; Drubach, Dina I.; Lee, Kendall H.; Lavrov, Igor A.
Spinal cord injury (SCI) remains a debilitating condition for which there is no cure. In addition to loss of somatic sensorimotor functions, SCI is also commonly associated with impairment of autonomic function. Importantly, cough dysfunction due to paralysis of expiratory muscles in combination with respiratory insufficiency can render affected individuals vulnerable to respiratory morbidity. Failure to clear sputum can aggravate both risk for and severity of respiratory infections, accounting for frequent hospitalizations and even mortality. Recently, epidural stimulation of the lower thoracic spinal cord has been investigated as novel means for restoring cough by evoking expiratory muscle contraction to generate large positive airway pressures and expulsive air flow. This review article discusses available preclinical and clinical evidence, current challenges and clinical potential of lower thoracic spinal cord stimulation (SCS) for restoring cough in individuals with SCI.
Hubli, Michèle; Krassioukov, Andrei V
Trauma to the spinal cord often results not only in sensorimotor but also autonomic impairments. The loss of autonomic control over the cardiovascular system can cause profound blood pressure (BP) derangements in subjects with spinal cord injury (SCI) and may therefore lead to increased cardiovascular disease (CVD) risk in this population. The use of ambulatory blood pressure monitoring (ABPM) allows insights into circadian BP profiles, which have been shown to be of good prognostic value for cardiovascular morbidity and mortality in able-bodied subjects. Past studies in SCI subjects using ABPM have shown that alterations in circadian BP patterns are dependent on the spinal lesion level. Tetraplegic subjects with sensorimotor complete lesions have a decreased daytime arterial BP, loss of the physiological nocturnal BP dip, and higher circadian BP variability, including potentially life-threatening hypertensive episodes known as autonomic dysreflexia (AD), compared with paraplegic and able-bodied subjects. The proposed underlying mechanisms of these adverse BP alterations mainly are attributed to a lost or decreased central drive to sympathetic spinal preganglionic neurons controlling the heart and blood vessels. In addition, several maladaptive anatomical changes within the spinal cord and the periphery, as well as the general decrease of physical daily activity in SCI subjects, account for adverse BP changes. ABPM enables the identification of adverse BP profiles and the associated increased risk for CVD in SCI subjects. Concurrently, it also might provide a useful clinical tool to monitor improvements of AD and lost nocturnal dip after appropriate treatments in the SCI population.
Thibault-Halman, Ginette; Casha, Steven
Abstract A systematic review of the literature was performed to address pertinent clinical questions regarding deep vein thrombosis (DVT) prophylaxis in the setting of acute spinal cord injury (SCI). Deep vein thromboses are a common occurrence following SCI. Administration of low-molecular-weight heparin (LMWH) within 72 h of injury is recommended to minimize the occurrence of DVT. Furthermore, when surgical intervention is required, LMWH should be held the morning of surgery, and resumed within 24 h post-operatively. PMID:20795870
Szarek, Dariusz; Marycz, Krzysztof; Lis, Anna; Zawada, Zbigniew; Tabakow, Paweł; Laska, Jadwiga; Jarmundowicz, Włodzimierz
Spinal cord injury (SCI) is a well-known devastating lesion that sadly is very resistant to all treatment attempts. This fact has stimulated the exploration of multiple regenerative strategies that are examined at both the basic and clinical level. For laboratory research, differentin vivomodels are used, but each has many important limitations. The main limitation of these models is the high level of animal suffering related to the inflicted neurologic injury. It has caused a growing tendency to limit the injury, but this, in turn, produces incomplete SCI models and uncertainties in the neuroregeneration interpretation. To overcome such limitations, a new experimental SCI model is proposed. Geckos have been extensively examined as a potential animal model of SCI. Their spinal cord extends into the tail and can be transected without causing the typical neurologic consequences observed in rat models. In this study, we compared the gecko tail SCI model with the rat model of thoracic SCI. Anatomic and histologic analyses showed comparability between the gecko and rat in diameter of spinal canal and spinal cord, as well as applicability of multiple staining techniques (hematoxylin and eosin, immunostaining, and scanning and transmission electron microscopy). We tested the suitability ofin vivostudy with 3 prototype implants for the reconstruction of SCI: a multichannel sponge, a multilaminar tube, and a gel cylinder. These were compared with a spinal cord excision (control). A 20-wk observation revealed no adverse effects of SCI on the animals' well-being. The animals were easily housed and observed. Histologic analysis showed growth of nervous tissue elements on implant surface and implant cellular colonization. The study showed that the gecko SCI model can be used as a primary model for the assessment of SCI treatment methods. It provides a platform for testing multiple solutions with limited animal suffering before performing tests on mammals. Detailed results of
Masmiquel, L; Simó, R; Galofré, P; Mesa, J
Cervical cord compression due to local extension of differentiated thyroid carcinoma (DTC) is an extremely rare condition and, to our knowledge, only one case has been reported in the literature. Among 256 patients with DTC treated at our hospital, we have observed 3 cases of spinal injury due to local extension of DTC. A Brown-Séquard syndrome was detected at physical examination in 2 cases. In both patients, cervical cord compression precipitated a fatal event. In the remaining patient, a radiculopathy C5-C7 was observed. Magnetic resonance imaging was very successful in outlining the mass, clearly differentiating the extrinsic invasion from a metastasis, and allowing the surgical possibilities to be evaluated. Poor cervical uptake of 131I was observed on scans performed in two cases, suggesting a certain degree of cell dedifferentiation. We suggest that cervical spinal injury due to local extension of DTC may be an underreported complication of DTC that seems to condition the patient's outcome. Careful neurological examination is warranted in patients with DTC at stages III-IV and magnetic resonance imaging must be performed when spinal injury is suspected.
ABSTRACT Essentially all spinal cord injured patients receive stretching therapies beginning within the first few weeks post-injury. Despite this fact...that stretching for short periods of time (4-5 weeks ) allows substantial recovery to occur once stretching is stopped, and both acute and chronic...4hours after one stretching session and then on Friday afternoon 3-4hours after the final stretching session of the week (the lowest scores). As seen
Anderberg, Leif; Aldskogius, Håkan; Holtz, Anders
The history of spinal cord injuries starts with the ancient Egyptian medical papyrus known as the Edwin Smith Surgical Papyrus. The papyrus written about 2500 B.C.by the physician and architect of the Sakkara pyramids Imhotep, describes "crushed vertebra in his neck" as well as symptoms of neurological deterioration. An ailment not to be treated was the massage to the patients at that time. This fatalistic attitude remained until the end of World War II when the first rehabilitation centre focused on the rehabilitation of spinal cord injured patients was opened. Our knowledge of the pathophysiological processes, both the primary as well as the secondary, has increased tremendously. However, all this knowledge has only led to improved medical care but not to any therapeutic method to restore, even partially, the neurological function. Neuroprotection is defined as measures to counteract secondary injury mechanisms and/or limit the extent of damage caused by self-destructive cellular and tissue processes. The co-existence of several distinctly different injury mechanisms after trauma has provided opportunities to explore a large number of potentially neuroprotective agents in animal experiments such as methylprednisolone sodium succinate. The results of this research have been very discouraging and pharmacological neuroprotection for patients with spinal cord injury has fallen short of the expectations created by the extensive research and promising observations in animal experiments. The focus of research has now, instead, been transformed to the field of neural regeneration. This field includes the discovery of regenerating obstacles in the nerve cell and/or environmental factors but also various regeneration strategies such as bridging the gap at the site of injury as well as transplantation of foetal tissue and stem cells. The purpose of this review is to highlight selected experimental and clinical studies that form the basis for undertaking future challenges in
Reintegration of Service-Members and Veterans with Spinal Cord Injury PRINCIPAL INVESTIGATOR: Seth D. Messinger, PhD... Reintegration of Service- 5a. CONTRACT NUMBER Members and Veterans with Spinal Cord Injury 5b. GRANT NUMBER W81XWH-11-1-0811 5c. PROGRAM ELEMENT... success . 15. SUBJECT TERMS Spinal Cord Injury, Community Reintegration , Qualitative Research 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF
AWARD NUMBER: W81XWH-14-2-0013 TITLE: DEVELOPMENT OF AN ANIMAL MODEL OF THORACOLUMBAR BURST FRACTURE - INDUCED ACUTE SPINAL CORD INJURY...2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER DEVELOPMENT OF AN ANIMAL MODEL OF THORACOLUMBAR BURST FRACTURE -INDUCED ACUTE SPINAL CORD INJURY 5b...leads to permanent disability following traumatic spine injury. A dramatic increase in blast related spinal burst fracture has been observed in
AWARD NUMBER: W81XWH-12-1-0559 TITLE: Treatment of Pain and Autonomic Dysreflexia in Spinal Cord Injury with Deep Brain Stimulation...Sep 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Treatment of Pain and Autonomic Dysreflexia in Spinal Cord Injury with Deep Brain...as a method for treating pain and autonomic dysreflexia in patients with chronic spinal cord injury (SCI). It is collaboration between the
Award Number: W81XWH-11-2-0213 TITLE: Family Caregivers for Veterans with Spinal Cord Injury: Exploring the Stresses and Benefits PRINCIPAL...TITLE AND SUBTITLE Family Caregivers for Veterans with Spinal Cord Injury: Exploring the Stresses 5a. CONTRACT NUMBER and Benefits 5b. GRANT NUMBER...Unfortunately, there are few studies that examine the intricacies of caregiving for people with spinal cord injuries. The purpose of this study is to
Wong, Kenneth H.; Choi, Jae; Wilson, William; Berry, Joel; Henderson, Fraser C., Sr.
Abnormal stretch and strain is a major cause of injury to the spinal cord and brainstem. Such forces can develop from age-related degeneration, congenital malformations, occupational exposure, or trauma such as sporting accidents, whiplash and blast injury. While current imaging technologies provide excellent morphology and anatomy of the spinal cord, there is no validated diagnostic tool to assess mechanical stresses exerted upon the spinal cord and brainstem. Furthermore, there is no current means to correlate these stress patterns with known spinal cord injuries and other clinical metrics such as neurological impairment. We have therefore developed the spinal cord stress injury assessment (SCOSIA) system, which uses imaging and finite element analysis to predict stretch injury. This system was tested on a small cohort of neurosurgery patients. Initial results show that the calculated stress values decreased following surgery, and that this decrease was accompanied by a significant decrease in neurological symptoms. Regression analysis identified modest correlations between stress values and clinical metrics. The strongest correlations were seen with the Brainstem Disability Index (BDI) and the Karnofsky Performance Score (KPS), whereas the weakest correlations were seen with the American Spinal Injury Association (ASIA) scale. SCOSIA therefore shows encouraging initial results and may have wide applicability to trauma and degenerative disease involving the spinal cord and brainstem.
Côté, Marie-Pascale; Gandhi, Sapan; Zambrotta, Marina; Houlé, John D
Activity-based therapies are routinely integrated in spinal cord injury (SCI) rehabilitation programs because they result in a reduction of hyperreflexia and spasticity. However, the mechanisms by which exercise regulates activity in spinal pathways to reduce spasticity and improve functional recovery are poorly understood. Persisting alterations in the action of GABA on postsynaptic targets is a signature of CNS injuries, including SCI. The action of GABA depends on the intracellular chloride concentration, which is determined largely by the expression of two cation-chloride cotransporters (CCCs), KCC2 and NKCC1, which serve as chloride exporters and importers, respectively. We hypothesized that the reduction in hyperreflexia with exercise after SCI relies on a return to chloride homeostasis. Sprague Dawley rats received a spinal cord transection at T12 and were assigned to SCI-7d, SCI-14d, SCI-14d+exercise, SCI-28d, SCI-28d+exercise, or SCI-56d groups. During a terminal experiment, H-reflexes were recorded from interosseus muscles after stimulation of the tibial nerve and the low-frequency-dependent depression (FDD) was assessed. We provide evidence that exercise returns spinal excitability and levels of KCC2 and NKCC1 toward normal levels in the lumbar spinal cord. Acutely altering chloride extrusion using the KCC2 blocker DIOA masked the effect of exercise on FDD, whereas blocking NKCC1 with bumetanide returned FDD toward intact levels after SCI. Our results indicate that exercise contributes to reflex recovery and restoration of endogenous inhibition through a return to chloride homeostasis after SCI. This lends support for CCCs as part of a pathway that could be manipulated to improve functional recovery when combined with rehabilitation programs.
Omar, N.; Srinivasan, M. S.
Whiplash injuries from motor vehicle accidents are very common. The usual presentation and course of this condition normally results in resolution of symptoms within a few weeks. Brachial plexus traction injuries without any bone or joint lesion of the cervical spine have been reported before. We report a case where a gentleman was involved in a rear end vehicle collision, sustained a whiplash injury and was later found to have a long thoracic nerve palsy and spinal accessory nerve palsy. Although isolated injuries of both nerves following a whiplash injury have been reported, combined injury of the two nerves following a whiplash injury is very uncommon and is being reported for the first time. PMID:17587067
Oshima, Toru; Hayashida, Mitsumasa; Ohtani, Maki; Hashimoto, Manabu; Takahashi, Satoshi; Ishiyama, Koichi; Otani, Takahiro; Koga, Makoto; Sugawara, Makoto; Mimasaka, Sohtaro
Although spine injuries are not always detectable on postmortem computed tomography (PMCT), spinal hyperostosis, an important risk factor for spine injury, is relatively easily detectable on PMCT. We therefore examined the utility of the detection of spinal hyperostosis on PMCT as an indicator of spine injury. Full-body PMCT images of 88 autopsy cases with a bruise on the face or forehead but no identifiable skull fracture were reviewed prior to autopsy for the identification and classification of spinal hyperostosis. Spine injuries were observed in 56.0% of cases with spinal hyperostosis and 1.6% of cases without spinal hyperostosis. Among the cases with spinal hyperostosis, spine injuries were observed in 66.7% of cases at stage 2 or 3 and in 88.9% of cases at stage 3. Spine injuries were diagnosed on PMCT in 33.3% of cases prior to autopsy. A significant association was found between spinal hyperostosis and presence of spine injury that cannot be detected on PMCT, indicating that the identification of spinal hyperostosis on PMCT may assist in detecting spine injuries. This finding suggests that investigation of the presence of spine injury based on the identification of spinal hyperostosis on PMCT may assist in determining the correct cause of death by autopsy.
Doulames, Vanessa M.; Plant, Giles W.
Cervical-level injuries account for the majority of presented spinal cord injuries (SCIs) to date. Despite the increase in survival rates due to emergency medicine improvements, overall quality of life remains poor, with patients facing variable deficits in respiratory and motor function. Therapies aiming to ameliorate symptoms and restore function, even partially, are urgently needed. Current therapeutic avenues in SCI seek to increase regenerative capacities through trophic and immunomodulatory factors, provide scaffolding to bridge the lesion site and promote regeneration of native axons, and to replace SCI-lost neurons and glia via intraspinal transplantation. Induced pluripotent stem cells (iPSCs) are a clinically viable means to accomplish this; they have no major ethical barriers, sources can be patient-matched and collected using non-invasive methods. In addition, the patient’s own cells can be used to establish a starter population capable of producing multiple cell types. To date, there is only a limited pool of research examining iPSC-derived transplants in SCI—even less research that is specific to cervical injury. The purpose of the review herein is to explore both preclinical and clinical recent advances in iPSC therapies with a detailed focus on cervical spinal cord injury. PMID:27070598
Yun, Hyun-Sik; Sun, Hyung-Seok; Seon, Hyo-Jeong; Han, Jae-Young; Choi, In-Sung
A 49-year-old man received prolotherapy in the upper cervical region at a local medical clinic. Immediately after the procedure, he felt a sensation resembling an electric shock in his right upper and lower extremities, and continuously complained of numbness and discomfort in the right hemibody. He visited our clinic a week later. Upon physical examination, there were no significant abnormal findings. The visual analog scale was 60 points. T2-weight magnetic resonance images of the cervical spine showed a 0.7 cm sized bright oval spot on the right side of the spinal cord at the level of C4-C5 disc, suggesting spinal cord injury. There were no definite electrodiagnostic abnormalities. Digital infrared thermal images showed moderately decreased surface temperature on lateral aspect of the right forearm and dorsum of the right hand compared with the other side. Considering that very rare complications like spinal cord injury may develop after prolotherapy, we suggest that special interventions such as prolotherapy be performed by professional experts. PMID:22506175
Yang, Cheng-Chang; Jou, I-Ming
Spinal cord injury (SCI) often results in some form of paralysis. Recently, SCI therapy has been focused on preventing secondary injury to reduce both neuroinflammation and lesion size so that functional outcome after an SCI may be improved. Previous studies have shown that adenosine receptors (AR) are a major regulator of inflammation after an SCI. The current study was performed to examine the effect of caffeine, a pan-AR blocker, on spontaneous functional recovery after an SCI. Animals were assigned into 3 groups randomly, including sham, PBS and caffeine groups. The rat SCI was generated by an NYU impactor with a 10 g rod dropped from a 25 mm height at thoracic 9 spinal cord level. Caffeine and PBS were injected daily during the experiment period. Hind limb motor function was evaluated by the Basso, Beattie, Bresnahan (BBB) locomotor rating scale at 1 week and 4 weeks after the SCI. Spinal cord segments were collected after final behavior evaluation for morphological analysis. The tissue sparing was evaluated by luxol fast blue staining. Immunofluorescence stain was employed to assess astrocyte activation and neurofilament positioning, while microglia activation was examined by immunohistochemistry stain.The results showed that spontaneous functional recovery was blocked after the animals were subjected caffeine daily. Moreover, caffeine administration increased the demyelination area, promoted astrocyte and microglia activation and decreased the quantity of neurofilaments. These findings suggest that the neurotoxicity effect of caffeine may be associated with the inhibition of neural repair and the promotion of neuroinflammation.
Popowitz, Richard L; Zvijac, John E; Uribe, John W; Hechtman, Keith S; Schürhoff, Matthias R; Green, Jeremy B
Previous studies on the treatment of rotator cuff tears in wheelchair-bound patients have concentrated on nonsurgical management. We conducted a retrospective review to determine the effectiveness of surgical repair of rotator cuff tears in spinal cord-injured patients. Five male patients with rotator cuff tears confirmed by physical examination and magnetic resonance imaging underwent rotator cuff repair. Two of eight shoulders were revisions. The patients were evaluated postoperatively with the American Shoulder and Elbow Surgeons Scoring System. These results were compared with preoperative functional assessment. Patients were given a subjective questionnaire to assess their overall experience. Postoperative range of motion improved in 6 of 8 shoulders. Strength was increased in 6 of 8 shoulders. Patients reported satisfaction with the results in 7 of 8 shoulders, and all 5 patients would recommend the procedure to other spinal cord injury patients. At recent follow-up, 7 of 8 shoulders returned to their preinjury level of function. Surgery for spinal cord injury patients with rotator cuff tears can improve their functional capability and autonomy while reducing their pain. Compliance with the demanding postoperative rehabilitation is essential; therefore proper patient selection is crucial for optimal results.
Aloe, Luigi; Bianchi, Patrizia; De Bellis, Alberto; Soligo, Marzia; Rocco, Maria Luisa
The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an increased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deficits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells. PMID:25206755
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. PMID:27303641
Cariga, P; Catley, M; Mathias, C; Savic, G; Frankel, H; Ellaway, P
Objectives: The sympathetic skin response (SSR) is a technique to assess the sympathetic cholinergic pathways, and it can be used to study the central sympathetic pathways in spinal cord injury (SCI). This study investigated the capacity of the isolated spinal cord to generate an SSR, and determined the relation between SSR, levels of spinal cord lesion, and supraspinal connections. Methods: Palmar and plantar SSR to peripheral nerve electrical stimulation (median or supraorbital nerve above the lesion, and peroneal nerve below the lesion) were recorded in 29 patients with SCI at various neurological levels and in 10 healthy control subjects. Results: In complete SCI at any neurological level, SSR was absent below the lesion. Palmar SSR to median nerve stimuli was absent in complete SCI with level of lesion above T6. Plantar SSR was absent in all patients with complete SCI at the cervical and thoracic level. In incomplete SCI, the occurrence of SSR was dependent on the preservation of supraspinal connections. For all stimulated nerves, there was no difference between recording from ipsilateral and contralateral limbs. Conclusions: No evidence was found to support the hypothesis that the spinal cord isolated from the brain stem could generate an SSR. The results indicate that supraspinal connections are necessary for the SSR, together with integrity of central sympathetic pathways of the upper thoracic segments for palmar SSR, and possibly all thoracic segments for plantar SSR. PMID:11861696
Myers, Scott A.; Andres, Kariena R.; Hagg, Theo; Whittemore, Scott R.
CD36 is a pleiotropic receptor involved in several pathophysiological conditions, including cerebral ischemia, neurovascular dysfunction and atherosclerosis, and recent reports implicate its involvement in the endoplasmic reticulum stress response (ERSR). We hypothesized that CD36 signaling contributes to the inflammation and microvascular dysfunction following spinal cord injury. Following contusive injury, CD36−/− mice demonstrated improved hindlimb functional recovery and greater white matter sparing than CD36+/+ mice. CD36−/− mice exhibited a reduced macrophage, but not neutrophil, infiltration into the injury epicenter. Fewer infiltrating macrophages were either apoptotic or positive for the ERSR marker, phospho-ATF4. CD36−/− mice also exhibited significant improvements in injury heterodomain vascularity and function. These microvessels accumulated less of the oxidized lipid product 4-hydroxy-trans-2-nonenal (4HNE) and exhibited a reduced ERSR, as detected by vascular phospho-ATF4, CHOP and CHAC-1 expression. In cultured primary endothelial cells, deletion of CD36 diminished 4HNE-induced phospho-ATF4 and CHOP expression. A reduction in phospho-eIF2α and subsequent increase in KDEL-positive, ER-localized proteins suggest that 4HNE-CD36 signaling facilitates the detection of misfolded proteins upstream of eIF2α phosphorylation, ultimately leading to CHOP-induced apoptosis. We conclude that CD36 deletion modestly, but significantly, improves functional recovery from spinal cord injury by enhancing vascular function and reducing macrophage infiltration. These phenotypes may, in part, stem from reduced ER stress-induced cell death within endothelial and macrophage cells following injury. PMID:24690303
Gazdic, Marina; Volarevic, Vladislav; Arsenijevic, Aleksandar; Erceg, Slaven; Moreno-Manzano, Victoria; Arsenijevic, Nebojsa; Stojkovic, Miodrag
Spinal cord injury (SCI) is a devastating condition that usually results in sudden and long-lasting locomotor and sensory neuron degeneration below the lesion site. During the last two decades, the search for new therapies has been revolutionized with the improved knowledge of stem cell (SC) biology. SCs therapy offers several attractive strategies for spinal cord repair. The transplantation of SCs promotes remyelination, neurite outgrowth and axonal elongation, and activates resident or transplanted progenitor cells across the lesion cavity. However, optimized growth and differentiation protocols along with reliable safety assays should be established prior to the clinical application of SCs. Additionally, the ideal method of SCs labeling for efficient cell tracking after SCI remains a challenging issue that requires further investigation. This review summarizes the current findings on the SCs-based therapeutic strategies, and compares different SCs labeling approaches for SCI. PMID:28035961
Tator, Charles H.; Edmonds, Virginia E.
Sports and recreation rose from the third to the second leading cause of spinal injuries treated in two Toronto hospitals between 1948 and 1983. Separate surveys of diving and hockey injuries are also reported. (Author/MT)
Albright, Theodore H.; Grabel, Zachary; DePasse, J. Mason; Palumbo, Mark A.
Sexual and reproductive health is important quality of life outcomes, which can have a major impact on patient satisfaction. Spinal pathology arising from trauma, deformity, and degenerative disease processes may be detrimental to sexual and reproductive function. Furthermore, spine surgery may impact sexual and reproductive function due to post-surgical mechanical, neurologic, and psychological factors. The aim of this paper is to provide a concise evidence-based review on the impact that spine surgery and pathology can have on sexual and reproductive function. A review of published literature regarding sexual and reproductive function in spinal injury and spinal surgery patients was performed. We have found that sexual and reproductive dysfunction can occur due to numerous etiological factors associated with spinal pathology. Numerous treatment options are available for those patients, depending on the degree of dysfunction. Spine surgeons and non-operative healthcare providers should be aware of the issues surrounding sexual and reproductive function as related to spine pathology and spine surgery. It is important for spine surgeons to educate their patients on the operative risks that spine surgery encompasses with regard to sexual dysfunction, although current data examining these topics largely consists of level IV data. PMID:26605025
Li, Ping; Teng, Zhao-Qian
Spinal cord injury is a devastating disease which disrupts the connections between the brain and spinal cord, often resulting in the loss of sensory and motor function below the lesion site. Most injured neurons fail to regenerate in the central nervous system after injury. Multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration after injury. MicroRNAs can modulate multiple genes' expression and are tightly controlled during nerve development or the injury process. Evidence has demonstrated that microRNAs and their signaling pathways play important roles in mediating axon regeneration and glial scar formation after spinal cord injury. This article reviews the role and mechanism of differentially expressed microRNAs in regulating axon regeneration and glial scar formation after spinal cord injury, as well as their therapeutic potential for promoting axonal regeneration and repair of the injured spinal cord. PMID:27818801
Abstract Trauma to the spinal cord often results not only in sensorimotor but also autonomic impairments. The loss of autonomic control over the cardiovascular system can cause profound blood pressure (BP) derangements in subjects with spinal cord injury (SCI) and may therefore lead to increased cardiovascular disease (CVD) risk in this population. The use of ambulatory blood pressure monitoring (ABPM) allows insights into circadian BP profiles, which have been shown to be of good prognostic value for cardiovascular morbidity and mortality in able-bodied subjects. Past studies in SCI subjects using ABPM have shown that alterations in circadian BP patterns are dependent on the spinal lesion level. Tetraplegic subjects with sensorimotor complete lesions have a decreased daytime arterial BP, loss of the physiological nocturnal BP dip, and higher circadian BP variability, including potentially life-threatening hypertensive episodes known as autonomic dysreflexia (AD), compared with paraplegic and able-bodied subjects. The proposed underlying mechanisms of these adverse BP alterations mainly are attributed to a lost or decreased central drive to sympathetic spinal preganglionic neurons controlling the heart and blood vessels. In addition, several maladaptive anatomical changes within the spinal cord and the periphery, as well as the general decrease of physical daily activity in SCI subjects, account for adverse BP changes. ABPM enables the identification of adverse BP profiles and the associated increased risk for CVD in SCI subjects. Concurrently, it also might provide a useful clinical tool to monitor improvements of AD and lost nocturnal dip after appropriate treatments in the SCI population. PMID:24175653
Franz, Steffen; Ciatipis, Mareva; Pfeifer, Kathrin; Kierdorf, Birthe; Sandner, Beatrice; Bogdahn, Ulrich; Blesch, Armin; Winner, Beate; Weidner, Norbert
After spinal cord injury, transected axons fail to regenerate, yet significant, spontaneous functional improvement can be observed over time. Distinct central nervous system regions retain the capacity to generate new neurons and glia from an endogenous pool of progenitor cells and to compensate neural cell loss following certain lesions. The aim of the present study was to investigate whether endogenous cell replacement (neurogenesis or gliogenesis) in the brain (subventricular zone, SVZ; corpus callosum, CC; hippocampus, HC; and motor cortex, MC) or cervical spinal cord might represent a structural correlate for spontaneous locomotor recovery after a thoracic spinal cord injury. Adult Fischer 344 rats received severe contusion injuries (200 kDyn) of the mid-thoracic spinal cord using an Infinite Horizon Impactor. Uninjured rats served as controls. From 4 to 14 days post-injury, both groups received injections of bromodeoxyuridine (BrdU) to label dividing cells. Over the course of six weeks post-injury, spontaneous recovery of locomotor function occurred. Survival of newly generated cells was unaltered in the SVZ, HC, CC, and the MC. Neurogenesis, as determined by identification and quantification of doublecortin immunoreactive neuroblasts or BrdU/neuronal nuclear antigen double positive newly generated neurons, was not present in non-neurogenic regions (MC, CC, and cervical spinal cord) and unaltered in neurogenic regions (dentate gyrus and SVZ) of the brain. The lack of neuronal replacement in the brain and spinal cord after spinal cord injury precludes any relevance for spontaneous recovery of locomotor function. Gliogenesis was increased in the cervical spinal cord remote from the injury site, however, is unlikely to contribute to functional improvement.
Pfeifer, Kathrin; Kierdorf, Birthe; Sandner, Beatrice; Bogdahn, Ulrich; Blesch, Armin; Winner, Beate; Weidner, Norbert
After spinal cord injury, transected axons fail to regenerate, yet significant, spontaneous functional improvement can be observed over time. Distinct central nervous system regions retain the capacity to generate new neurons and glia from an endogenous pool of progenitor cells and to compensate neural cell loss following certain lesions. The aim of the present study was to investigate whether endogenous cell replacement (neurogenesis or gliogenesis) in the brain (subventricular zone, SVZ; corpus callosum, CC; hippocampus, HC; and motor cortex, MC) or cervical spinal cord might represent a structural correlate for spontaneous locomotor recovery after a thoracic spinal cord injury. Adult Fischer 344 rats received severe contusion injuries (200 kDyn) of the mid-thoracic spinal cord using an Infinite Horizon Impactor. Uninjured rats served as controls. From 4 to 14 days post-injury, both groups received injections of bromodeoxyuridine (BrdU) to label dividing cells. Over the course of six weeks post-injury, spontaneous recovery of locomotor function occurred. Survival of newly generated cells was unaltered in the SVZ, HC, CC, and the MC. Neurogenesis, as determined by identification and quantification of doublecortin immunoreactive neuroblasts or BrdU/neuronal nuclear antigen double positive newly generated neurons, was not present in non-neurogenic regions (MC, CC, and cervical spinal cord) and unaltered in neurogenic regions (dentate gyrus and SVZ) of the brain. The lack of neuronal replacement in the brain and spinal cord after spinal cord injury precludes any relevance for spontaneous recovery of locomotor function. Gliogenesis was increased in the cervical spinal cord remote from the injury site, however, is unlikely to contribute to functional improvement. PMID:25050623
Pahys, Joshua M; Mulcahey, M.J; Hutchinson, David; Betz, Randal R
Background: Severe scapular instability can be a considerable problem for people with high-level cervical spinal cord injury. Scapular instability reduces the effectiveness of the already weakened shoulder flexors and abductors, thereby limiting hand-to-mouth and hand-to-head activities. The winged scapula may cause inferior pole skin breakdown, as well as neck and shoulder pain. Objective: To report the efficacy of a fusionless scapular stabilization procedure as a means to enhance function in a consecutive group of patients with high-level cervical spinal cord injury. Methods: Four people with spinal cord injury at C4–C5 (2 male, 2 female; mean age = 17.3 years, range = 14–20 years) underwent scapular stabilization via scapulothoracic fusion (N = 2) or by tethering the scapula to the rib cage with Mersilene tape as a fusionless stabilization (N = 2). One patient died of unrelated causes 18 months after surgery, and the remaining 3 were followed for 26, 39, and 41 months, respectively. Data collection included radiographic analysis, active range of motion measures, and functional assessment. Results: Active shoulder flexion and abduction remained unchanged in 2 patients, but functional scores improved with regard to feeding and grooming capability. All patients reported satisfaction with postoperative appearance, and 3 patients reported considerable reduction in shoulder pain after surgery. Radiographs demonstrated maintenance of stable scapular alignment in all patients at final follow up. Wound breakdown, requiring removal of instrumentation, occurred in 2 patients. Conclusion: Scapular stabilization with or without fusion is a viable option to improve appearance, pain, and upper extremity function in people with high-level tetraplegia and scapular instability. PMID:19777859
Hagen, Ellen M; Rekand, Tiina
Spinal cord injury (SCI) is an injury to the spinal cord that leads to varying degrees of motor and/or sensory deficits and paralysis. Chronic pain of both neuropathic and nociceptive type is common and contributes to reduced quality of life. The aim of the review is to provide current clinical understanding as well as discuss and evaluate efficacy of pharmacological interventions demonstrated in the clinical studies. The review was based on literature search in PubMed and Medline with words "neuropathic pain" and "spinal cord injury". The review included clinical studies and not experimental data nor case reports. A limited number of randomized and placebo-controlled studies concerning treatment options of neuropathic pain after SCI were identified. Amitriptyline, a tricyclic antidepressant and the antiepileptic drugs, gabapentin and pregabalin, are most studied with demonstrated efficacy, and considered to be the primary choice. Opioids have demonstrated conflicting results in the clinical studies. In addition, administration route used in the studies as well as reported side effects restrict everyday use of opioids as well as ketamine and lidocaine. Topical applications of capsaicin or lidocaine as well as intradermal injections of Botulinum toxin are new treatment modalities that are so far not studied on SCI population and need further studies. Non-pharmacological approaches may have additional effect on neuropathic pain. Management of pain should always be preceded by thorough clinical assessment of the type of pain. Patients need a follow-up to evaluate individual effect of applied measures. However, the applied management does not necessarily achieve satisfactory pain reduction. Further clinical studies are needed to evaluate the effect of both established and novel management options.
Abud, Edsel M; Ichiyama, Ronaldo M; Havton, Leif A; Chang, Huiyi H
After spinal cord injury (SCI), the neurogenic bladder is observed to develop asynchronous bladder and external urethral sphincter (EUS) contractions in a condition known as detrusor-sphincter dyssnergia (DSD). Activation of the EUS spinal controlling center located at the upper lumbar spinal cord may contribute to reduce EUS dyssynergic contractions and decrease urethral resistance during voiding. However, this mechanism has not been well studied. This study aimed at evaluating the effects of epidural stimulation (EpS) over the spinal EUS controlling center (L3) in combination with a serotonergic receptor agonist on EUS relaxation in naive rats and chronic (6-8 wk) T8 SCI rats. Cystometrogram and EUS electromyography (EMG) were obtained before and after the intravenous administration of 5HT-1A receptor agonist and antagonist. The latency, duration, frequency, amplitude, and area under curve of EpS-evoked EUS EMG responses were analyzed. EpS on L3 evoked an inhibition of EUS tonic contraction and an excitation of EUS intermittent bursting/relaxation correlating with urine expulsion in intact rats. Combined with a 5HT-1A receptor agonist, EpS on L3 evoked a similar effect in chronic T8 SCI rats to reduce urethral contraction (resistance). This study examined the effect of facilitating the EUS spinal controlling center to switch between urine storage and voiding phases by using EpS and a serotonergic receptor agonist. This novel approach of applying EpS on the EUS controlling center modulates EUS contraction and relaxation as well as reduces urethral resistance during voiding in chronic SCI rats with DSD.
Lin, Chia-Ching; Lai, Sih-Rong; Shao, Yu-Han; Chen, Chun-Lin; Lee, Kun-Ze
Respiratory impairment due to damage of the spinal respiratory motoneurons and interruption of the descending drives from brainstem premotor neurons to spinal respiratory motoneurons is the leading cause of morbidity and mortality following cervical spinal cord injury. The present study was designed to evaluate the therapeutic effectiveness of delayed transplantation of fetal spinal cord (FSC) tissue on respiratory function in rats with mid-cervical spinal cord injury. Embryonic day-14 rat FSC tissue was transplanted into a C4 spinal cord hemilesion cavity in adult male rats at 1 week postinjury. The histological results showed that FSC-derived grafts can survive, fill the lesion cavity, and differentiate into neurons and astrocytes at 8 weeks post-transplantation. Some FSC-derived graft neurons exhibited specific neurochemical markers of neurotransmitter (e.g., serotonin, noradrenalin, or acetylcholine). Moreover, a robust expression of glutamatergic and γ-aminobutyric acid-ergic fibers was observed within FSC-derived grafts. Retrograde tracing results indicated that there was a connection between FSC-derived grafts and host phrenic nucleus. Neurophysiological recording of the phrenic nerve demonstrated that phrenic burst amplitude ipsilateral to the lesion was significantly greater in injured animals that received FSC transplantation than in those that received buffer transplantation under high respiratory drives. These results suggest that delayed FSC transplantation may have the potential to repair the injured spinal cord and promote respiratory functional recovery after mid-cervical spinal cord injury.
Granger, Nicolas; Carwardine, Darren
Spinal cord injury (SCI) is a common problem in animals for which definitive treatment is lacking, and information gained from its study has benefit for both companion animals and humans in developing new therapeutic approaches. This review provides an overview of the main concepts that are useful for clinicians in assessing companion animals with severe acute SCI. Current available advanced ancillary tests and those in development are reviewed. In addition, the current standard of care for companion animals following SCI and recent advances in the development of new therapies are presented, and new predictors of recovery discussed.
Ludwig Guttmann was a pioneer of the idea of rehabilitation for victims of spinal cord injury. He looked beyond the physical survival of his patients, to their re-integration into a social life worth living. While the International Stoke Mandeville Games are fairly well known to the general public as a gathering for physically handicapped athletes, less is known about the man who helped start the movement. On the occasion of the recent Sydney 2000 Paralympics, this paper reviews the contribution of Ludwig Guttmann, who introduced sport into the life of paralyzed patients.
Ros, C; de la Fuente, C; Pumarola, M; Añor, S
A 13-year-old, female spayed, crossbreed dog of 32 kg was presented for evaluation of peracute onset of non-ambulatory tetraparesis after chewing an electrical wire. Neurological examination was consistent with a C1-C5 myelopathy. Magnetic resonance imaging revealed a focal intramedullary lesion over the C2-C3 vertebral bodies, which was confirmed to be an acute focal necrotising poliomyelopathy with subarachnoid and subdural haemorrhages on postmortem examination. This report describes the clinical, imaging and histopathological findings of this unusual type of spinal cord injury, and the effects of electrocution in the central nervous system of dogs.
Hu, Ji; Yu, Qijing; Xie, Lijie; Zhu, Hongfei
One of the principal functions of physical barriers between the blood and central nervous system protects system (i.e., blood brain barrier and blood-spinal cord barrier) is the protection from toxic and pathogenic agents in the blood. Disruption of blood-spinal cord barrier (BSCB) plays a key role in spinal cord ischemia-reperfusion injury (SCIRI). Following SCIRI, the permeability of the BSCB increases. Maintaining the integrity of the BSCB alleviates the spinal cord injury after spinal cord ischemia. This review summarizes current knowledge of the structure and function of the BSCB and its changes following SCIRI, as well as the prevention and cure of SCIRI and the role of the BSCB.
Charlifue, S W; Gerhart, K A; Menter, R R; Whiteneck, G G; Manley, M S
The need for research addressing problems unique to women with spinal cord injuries is well documented. Consequently, 231 such women, ages 18 to 45, were surveyed. Demographic characteristics and data relating to physician usage, female hygiene, pregnancy, contraception and sexuality were collected. Analysis revealed that 60% of the respondents had post injury amenorrhea; the average time until menses resumption was 5 months. The group's post injury pregnancy rate was one-third its pre injury rate, but women with incomplete paraplegia had significantly more pregnancies than those with complete quadriplegia. Of 47 women who did carry babies to delivery, one-half had vaginal deliveries; 49% used no anesthesia. Problems during pregnancy included autonomic hyperreflexia, decubitus ulcers, urinary tract infections, water retention, bladder and bowel problems, anemia, spotting, fatigue, cardiac irregularity and toxemia. Many of these problems plagued the women during labor and delivery and in the post partum period as well. Sixty-nine percent of the women were satisfied with their post injury sexual experiences, although self confidence, spasticity, and lack of spontaneity were issues. Although satisfied with care received from physicians, many women were not content with the information provided during rehabilitation, and felt a need for more literature, counselling, and peer support.
Dasch, Kimberly B; Russell, Heather F; Kelly, Erin H; Gorzkowski, Julie A; Mulcahey, Mary Jane; Betz, Randal R; Vogel, Lawrence C
This study examined coping among caregivers of youth with spinal cord injuries (SCI). Using a cross-sectional survey study design, 164 caregivers completed a demographics questionnaire and the Brief COPE. Their children, youth with SCI ages 7-18, completed the Kidcope. T-tests were conducted to examine differences in caregiver coping by demographic and injury-related factors. Further, logistic regression models were evaluated to examine predictive relationships between caregiver coping and youth coping. Several demographic and injury-related factors were related to caregiver coping, including caregiver gender, race, and education, as well as youth gender, age at injury, and time since injury. In the logistic regressions, two caregiver coping strategies were related to youth coping: caregiver self-blame coping was related to youth self-criticism, and caregiver behavioral disengagement coping (giving up attempts to cope) was related to youth blaming others coping. The findings suggest that caregiver coping may play a role in the coping of their children, and should be considered when addressing coping among youth with SCI.
Anna, Zadroga; Joanna, Czarzasta; Barczewska, Monika; Wojciech, Maksymowicz
Spinal cord injury (SCI) is a devastating neurological condition that affects individuals worldwide, significantly reducing quality of life, for both patients and their families. In recent years there has been a growing interest in cell therapy potential in the context of spinal cord injuries. The present review aims to discuss and compare the restorative approaches based on the current knowledge, available spinal cord restorative cell therapies, and use of selected cell types. However, treatment options for spinal cord injury are limited, but rehabilitation and experimental technologies have been found to help maintain or improve remaining nerve function in some cases. Mesenchymal stem cells as well as olfactory ensheathing cells seem to show therapeutic impact on damaged spinal cord and might be useful in neuroregeneration. Recent research in animal models and first human trials give patients with spinal cord injuries hope for recovery. PMID:28298927
Anna, Zadroga; Katarzyna, Jezierska-Woźniak; Joanna, Czarzasta; Barczewska, Monika; Joanna, Wojtkiewicz; Wojciech, Maksymowicz
Spinal cord injury (SCI) is a devastating neurological condition that affects individuals worldwide, significantly reducing quality of life, for both patients and their families. In recent years there has been a growing interest in cell therapy potential in the context of spinal cord injuries. The present review aims to discuss and compare the restorative approaches based on the current knowledge, available spinal cord restorative cell therapies, and use of selected cell types. However, treatment options for spinal cord injury are limited, but rehabilitation and experimental technologies have been found to help maintain or improve remaining nerve function in some cases. Mesenchymal stem cells as well as olfactory ensheathing cells seem to show therapeutic impact on damaged spinal cord and might be useful in neuroregeneration. Recent research in animal models and first human trials give patients with spinal cord injuries hope for recovery.
This study sought to evaluate the body composition of subjects with active spinal cord injuries and polio. Two groups of males and females, active, free-living, of similar ages and body mass index (BMI), were distributed according to the source of deficiency: SCI – low spinal cord injury (T5-T12) an...
Marini, Irmo; Glover-Graf, Noreen M.
A total of 157 persons with spinal cord injury completed the "Spirituality and Spinal Cord Injury Survey" in relation to their spiritual and/or religious attitudes, beliefs, and practices in terms of adapting to their disability. Factor analysis accounting for 69% of the variance revealed four factors related to Spiritual Help and Improvement…
Crewe, Nancy M.
Uses interviews conducted in 1974 and 1994 to investigate the vocational experiences of individuals with spinal cord injuries. Participants had received a spinal cord injury 22-45 years previously. Results revealed that all but seven of the participants had been in remunerative employment. Work experiences, comprehensive rehabilitation service,…
Kiwerski, J. E.; Krasuski, M.
This study compared the neurological state and results of treatment for patients with traumatic spinal cord injury who were intoxicated (n=424) or sober (n=769) on admission to a Warsaw (Poland) hospital. In the intoxicated group, the number of patients with symptoms of complete spinal cord injury was much greater than that of the sober group. (DB)
Zhang, Qian; Wang, Jianbo; Gu, Zhengsong; Zhang, Qing; Zheng, Hong
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.
Bone Architechture in Chronic Spinal Cord Injury Effect of Teriparatide, Vibration and the Combination on Bone Mass and Bone Architechture in Chronic... Spinal Cord Injury 5a. CONTRACT NUMBER W81XWH-10-1-0951 Mass and Bone Architecture in Chronic Spinal Cord Injury 5b. GRANT NUMBER 5c. PROGRAM...distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Severe bone loss commonly occurs in individuals with chronic spinal cord injury who are non
Stirling, David P; Cummins, Karen; Mishra, Manoj; Teo, Wulin; Yong, V Wee; Stys, Peter
Improving neurological outcome after spinal cord injury is a major clinical challenge because axons, once severed, do not regenerate but 'dieback' from the lesion site. Although microglia, the immunocompetent cells of the brain and spinal cord respond rapidly to spinal cord injury, their role in subsequent injury or repair remains unclear. To assess the role of microglia in spinal cord white matter injury we used time-lapse two-photon and spectral confocal imaging of green fluorescent protein-labelled microglia, yellow fluorescent protein-labelled axons, and Nile Red-labelled myelin of living murine spinal cord and revealed dynamic changes in white matter elements after laser-induced spinal cord injury in real time. Importantly, our model of acute axonal injury closely mimics the axonopathy described in well-characterized clinically relevant models of spinal cord injury including contusive-, compressive- and transection-based models. Time-lapse recordings revealed that microglia were associated with some acute pathophysiological changes in axons and myelin acutely after laser-induced spinal cord injury. These pathophysiological changes included myelin and axonal spheroid formation, spectral shifts in Nile Red emission spectra in axonal endbulbs detected with spectral microscopy, and 'bystander' degeneration of axons that survived the initial injury, but then succumbed to secondary degeneration. Surprisingly, modulation of microglial-mediated release of neurotoxic molecules failed to protect axons and myelin. In contrast, sterile stimulation of microglia with the specific toll-like receptor 2 agonist Pam2CSK4 robustly increased the microglial response to ablation, reduced secondary degeneration of central myelinated fibres, and induced an alternative (mixed M1:M2) microglial activation profile. Conversely, Tlr2 knock out: Thy1 yellow fluorescent protein double transgenic mice experienced greater axonal dieback than littermate controls. Thus, promoting an alternative
Award Number: W81XWH-11-1-0797 TITLE: Matrix metalloproteinases as a therapeutic target to improve neurologic recovery after spinal cord injury...after spinal cord injury 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0797 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Linda J. Noble, Alpa...SUPPLEMENTARY NOTES 14. ABSTRACT Purpose: We are evaluating efficacy of GM6001, a matrix metalloproteinase (MMP) inhibitor in a murine model of spinal cord
Award Number: Contract #: W81XWH-13-1-0410 TITLE: "Respiratory Plasticity Following Spinal Injury: Role of Chloride-Dependent Inhibitory...13-1-0410 "Respiratory Plasticity Following Spinal Injury: Role of Chloride-Dependent Inhibitory Neurotransmission" 5b. GRANT NUMBER SC120226...induced plasticity in chloride-dependent synaptic inhibition of phrenic motor neurons contributes to functional recovery from chronic cervical spinal
Galeiras Vázquez, Rita; Rascado Sedes, Pedro; Montoto Marqués, Antonio; Ferreiro Velasco, M. Elena
Spinal cord injuries (SCIs) often lead to impairment of the respiratory system and, consequently, restrictive respiratory changes. Paresis or paralysis of the respiratory muscles can lead to respiratory insufficiency, which is dependent on the level and completeness of the injury. Respiratory complications include hypoventilation, a reduction in surfactant production, mucus plugging, atelectasis, and pneumonia. Vital capacity (VC) is an indicator of overall pulmonary function; patients with severely impaired VC may require assisted ventilation. It is best to proceed with intubation under controlled circumstances rather than waiting until the condition becomes an emergency. Mechanical ventilation can adversely affect the structure and function of the diaphragm. Early tracheostomy following short orotracheal intubation is probably beneficial in selected patients. Weaning should start as soon as possible, and the best modality is progressive ventilator-free breathing (PVFB). Appropriate candidates can sometimes be freed from mechanical ventilation by electrical stimulation. Respiratory muscle training regimens may improve patients' inspiratory function following a SCI. PMID:24089664
Anderson, Kim D.; Sharp, Kelli G.; Steward, Oswald
There is increasing motivation to develop clinically relevant experimental models for cervical SCI in rodents and techniques to assess deficits in forelimb function. Here we describe a bilateral cervical contusion model in rats. Female Sprague-Dawley rats received mild or moderate cervical contusion injuries (using the Infinite Horizons device) at C5, C6, or C7/8. Forelimb motor function was assessed using a Grip Strength Meter (GSM); sensory function was assessed by the von Frey hair test; the integrity of the corticospinal tract (CST) was assessed by biotinylated dextran amine (BDA) tract tracing. Mild contusions caused primarily dorsal column (DC) and gray matter (GM) damage while moderate contusions produced additional damage to lateral and ventral tissue. Forelimb and hindlimb function was severely impaired immediately post-injury, but all rats regained the ability to use their hindlimbs for locomotion. Gripping ability was abolished immediately after injury but recovered partially, depending upon the spinal level and severity of the injury. Rats exhibited a loss of sensation in both fore- and hindlimbs that partially recovered, and did not exhibit allodynia. Tract tracing revealed that the main contingent of CST axons in the DC was completely interrupted in all but one animal whereas the dorsolateral CST (dlCST) was partially spared, and dlCST axons gave rise to axons that arborized in the GM caudal to the injury. Our data demonstrate that rats can survive significant bilateral cervical contusion injuries at or below C5 and that forepaw gripping function recovers after mild injuries even when the main component of CST axons in the dorsal column is completely interrupted. PMID:19559699
Reier, Paul J
Basic science advances in spinal cord injury and regeneration research have led to a variety of novel experimental therapeutics designed to promote functionally effective axonal regrowth and sprouting. Among these interventions are cell-based approaches involving transplantation of neural and non-neural tissue elements that have potential for restoring damaged neural pathways or reconstructing intraspinal synaptic circuitries by either regeneration or neuronal/glial replacement. Notably, some of these strategies (e.g., grafts of peripheral nerve tissue, olfactory ensheathing glia, activated macrophages, marrow stromal cells, myelin-forming oligodendrocyte precursors or stem cells, and fetal spinal cord tissue) have already been translated to the clinical arena, whereas others have imminent likelihood of bench-to-bedside application. Although this progress has generated considerable enthusiasm about treating what once was thought to be a totally incurable condition, there are many issues to be considered relative to treatment safety and efficacy. The following review reflects on different experimental applications of intraspinal transplantation with consideration of the underlying pathological, pathophysiological, functional, and neuroplastic responses to spinal trauma that such treatments may target along with related issues of procedural and biological safety. The discussion then moves to an overview of ongoing and completed clinical trials to date. The pros and cons of these endeavors are considered, as well as what has been learned from them. Attention is primarily directed at preclinical animal modeling and the importance of patterning clinical trials, as much as possible, according to laboratory experiences.
... Spinal Cord Injuries Program? 359.1 Section 359.1 Education Regulations of the Offices of the Department... EDUCATION DISABILITY AND REHABILITATION RESEARCH: SPECIAL PROJECTS AND DEMONSTRATIONS FOR SPINAL CORD INJURIES General § 359.1 What is the Special Projects and Demonstrations for Spinal Cord Injuries...
... Spinal Cord Injuries Program? 359.1 Section 359.1 Education Regulations of the Offices of the Department... EDUCATION DISABILITY AND REHABILITATION RESEARCH: SPECIAL PROJECTS AND DEMONSTRATIONS FOR SPINAL CORD INJURIES General § 359.1 What is the Special Projects and Demonstrations for Spinal Cord Injuries...
... Spinal Cord Injuries Program? 359.1 Section 359.1 Education Regulations of the Offices of the Department... EDUCATION DISABILITY AND REHABILITATION RESEARCH: SPECIAL PROJECTS AND DEMONSTRATIONS FOR SPINAL CORD INJURIES General § 359.1 What is the Special Projects and Demonstrations for Spinal Cord Injuries...
Tator, C H; Fehlings, M G
In patients with spinal cord injury, the primary or mechanical trauma seldom causes total transection, even though the functional loss may be complete. In addition, biochemical and pathological changes in the cord may worsen after injury. To explain these phenomena, the concept of the secondary injury has evolved for which numerous pathophysiological mechanisms have been postulated. This paper reviews the concept of secondary injury with special emphasis on vascular mechanisms. Evidence is presented to support the theory of secondary injury and the hypothesis that a key mechanism is posttraumatic ischemia with resultant infarction of the spinal cord. Evidence for the role of vascular mechanisms has been obtained from a variety of models of acute spinal cord injury in several species. Many different angiographic methods have been used for assessing microcirculation of the cord and for measuring spinal cord blood flow after trauma. With these techniques, the major systemic and local vascular effects of acute spinal cord injury have been identified and implicated in the etiology of secondary injury. The systemic effects of acute spinal cord injury include hypotension and reduced cardiac output. The local effects include loss of autoregulation in the injured segment of the spinal cord and a marked reduction of the microcirculation in both gray and white matter, especially in hemorrhagic regions and in adjacent zones. The microcirculatory loss extends for a considerable distance proximal and distal to the site of injury. Many studies have shown a dose-dependent reduction of spinal cord blood flow varying with the severity of injury, and a reduction of spinal cord blood flow which worsens with time after injury. The functional deficits due to acute spinal cord injury have been measured electrophysiologically with techniques such as motor and somatosensory evoked potentials and have been found proportional to the degree of posttraumatic ischemia. The histological effects
Lusilla-Palacios, Pilar; Castellano-Tejedor, Carmina
Background. An acute spinal cord injury (ASCI) is a severe condition that requires extensive and very specialized management of both physical and psychological dimensions of injured patients. Objective. The aim of the part of the study reported here was twofold: (1) to describe burnout, empathy, and satisfaction at work of these professionals and (2) to explore whether a tailored program based on motivational interviewing (MI) techniques modifies and improves such features. Methods. This paper presents findings from an intervention study into a tailored training for professionals (N = 45) working in a spinal cord injury (SCI) unit from a general hospital. Rehabilitation professionals' empathy skills were measured with the Jefferson Scale of Physician Empathy (JSPE), burnout was measured with the Maslach Burnout Inventory (MBI), and additional numeric scales were used to assess the perceived job-related stress and perceived satisfaction with job. Results. Findings suggest that professionals are performing quite well and they refer to satisfactory empathy, satisfaction at work, and no signs of burnout or significant stress both before and after the training. Conclusions. No training effect was observed in the variables considered in the study. Some possible explanations for these results and future research directions are discussed in depth in this paper. The full protocol of this study is registered in ClinicalTrials.gov (identifier: NCT01889940). PMID:26770827
Background and Purpose The long-term management following an hemicorporectomy (HCP) is not well documented in the scientific literature. The purpose of this case report is to describe the 25-year history of a man with a spinal cord injury who experienced severe musculoskeletal deterioration and hemicorporectomy. Case Description The client sustained T10 complete paraplegia at age 18 years, developed severe decubitus ulcers, and required an HCP as a lifesaving measure 13 years later. The authors describe the chronology of several rehabilitation and prosthetic strategies and speculate on factors that may have contributed to their successes and failures. Outcomes The client survived 12 years after the HCP and returned to independent mobility, self-care, and schooling despite complications with continued skin breakdown. Over the 12 years following discharge from the hospital after the spinal cord injury, he spent 749 days in the hospital. During the 12 years he lived after discharge from the hospital following the HCP, he was hospitalized 190 days. Discussion The authors discuss factors contributing to the client’s musculoskeletal deterioration including chronic wounds, postural deviations, and incomplete adherence to pressure-relief recommendations and raise considerations for physical therapists who treat patients after HCP. PMID:12620090
Assunção-Silva, Rita C.; Gomes, Eduardo D.; Silva, Nuno A.; Salgado, António J.
Spinal cord injury (SCI) is a central nervous system- (CNS-) related disorder for which there is yet no successful treatment. Within the past several years, cell-based therapies have been explored for SCI repair, including the use of pluripotent human stem cells, and a number of adult-derived stem and mature cells such as mesenchymal stem cells, olfactory ensheathing cells, and Schwann cells. Although promising, cell transplantation is often overturned by the poor cell survival in the treatment of spinal cord injuries. Alternatively, the therapeutic role of different cells has been used in tissue engineering approaches by engrafting cells with biomaterials. The latter have the advantages of physically mimicking the CNS tissue, while promoting a more permissive environment for cell survival, growth, and differentiation. The roles of both cell- and biomaterial-based therapies as single therapeutic approaches for SCI repair will be discussed in this review. Moreover, as the multifactorial inhibitory environment of a SCI suggests that combinatorial approaches would be more effective, the importance of using biomaterials as cell carriers will be herein highlighted, as well as the recent advances and achievements of these promising tools for neural tissue regeneration. PMID:26124844
Tancredo, Janaina Roland; Maria, Renata Manzano; de Azevedo, Eliza Regina Ferreira Braga Machado; Alonso, Karina Cristina; Varoto, Renato; Cliquet, Alberto
Objective To evaluate the effect of neuromuscular electrical stimulation on spasticity in patients with spinal cord injury. Methods The study included eleven subjects with spinal cord injuries (C4 to T5). The modified Ashworth scale and pendulum test, which is accomplished through the Pendular Test Device - PTD (equipment which has a quartz crystal transducer accelerometer and optic fiber flexible electrogoniometer measuring the tensions and angular displacements). Patients underwent neuromuscular electrical stimulation (NMES) to the quadriceps muscle from fibular nerve, and the tests were administered before and after therapy. Results The data show a decrease in spasticity after NMES, with features such as increased variation between maximum and minimum peaks, i.e. increased amplitude of the curves. Furthermore, data from the subjective scale, and modified Ashworth scale after neuromuscular electrical stimulation also showed a reduction in the values of spasticity. Conclusion The data suggest that NMES is effective in reducing spasticity immediately after completion. Level of Evidence II, Therapeutic Studies-Investigating the Results of Treatment. PMID:24453687
Jöbsis, Jasper J; Alabbas, Abdullah; Milner, Ruth; Reilly, Christopher; Mulpuri, Kishore; Mammen, Cherry
AIM To determine acute kidney in jury (AKI) incidence and potential risk factors of AKI in children undergoing spinal instrumentation surgery. METHODS AKI incidence in children undergoing spinal instrumentation surgery at British Columbia Children’s Hospital between January 2006 and December 2008 was determined by the Acute Kidney Injury Networ classification using serum creatinine and urine output criteria. During this specific time period, all patients following spinal surgery were monitored in the pediatric intensive care unit and had an indwelling Foley catheter permitting hourly urine output recording. Cases of AKI were identified from our database. From the remaining cohort, we selected group-matched controls that did not satisfy criteria for AKI. The controls were matched for sex, age and underlying diagnosis (idiopathic vs non-idiopathic scoliosis). RESULTS Thirty five of 208 patients met criteria for AKI with an incidence of 17% (95%CI: 12%-23%). Of all children who developed AKI, 17 (49%) developed mild AKI (AKI Stage 1), 17 (49%) developed moderate AKI (Stage 2) and 1 patient (3%) met criteria for severe AKI (Stage 3). An inverse relationship was observed with AKI incidence and the amount of fluids received intra-operatively. An inverse relationship was observed with AKI incidence and the amount of fluids received intra-operatively classified by fluid tertiles: 70% incidence in those that received the least amount of fluids vs 29% that received the most fluids (> 7.9, P = 0.02). Patients who developed AKI were more frequently exposed to nephrotoxins (non steroidal anti inflammatory drugs or aminoglycosides) than control patients during their peri-operative course (60% vs 22%, P < 0.001). CONCLUSION We observed a high incidence of AKI following spinal instrumentation surgery in children that is potentially related to the frequent use of nephrotoxins and the amount of fluid administered peri-operatively. PMID:28316941
Bunday, Karen L; Tazoe, Toshiki; Rothwell, John C; Perez, Monica A
The motor cortex and the corticospinal system contribute to the control of a precision grip between the thumb and index finger. The involvement of subcortical pathways during human precision grip remains unclear. Using noninvasive cortical and cervicomedullary stimulation, we examined motor evoked potentials (MEPs) and the activity in intracortical and subcortical pathways targeting an intrinsic hand muscle when grasping a small (6 mm) cylinder between the thumb and index finger and during index finger abduction in uninjured humans and in patients with subcortical damage due to incomplete cervical spinal cord injury (SCI). We demonstrate that cortical and cervicomedullary MEP size was reduced during precision grip compared with index finger abduction in uninjured humans, but was unchanged in SCI patients. Regardless of whether cortical and cervicomedullary stimulation was used, suppression of the MEP was only evident 1-3 ms after its onset. Long-term (∼5 years) use of the GABAb receptor agonist baclofen by SCI patients reduced MEP size during precision grip to similar levels as uninjured humans. Index finger sensory function correlated with MEP size during precision grip in SCI patients. Intracortical inhibition decreased during precision grip and spinal motoneuron excitability remained unchanged in all groups. Our results demonstrate that the control of precision grip in humans involves premotoneuronal subcortical mechanisms, likely disynaptic or polysynaptic spinal pathways that are lacking after SCI and restored by long-term use of baclofen. We propose that spinal GABAb-ergic interneuronal circuits, which are sensitive to baclofen, are part of the subcortical premotoneuronal network shaping corticospinal output during human precision grip.
Fernández-López, Blanca; Barreiro-Iglesias, Antón; Rodicio, María Celina
Lampreys recover locomotion following a spinal cord injury (SCI). Glutamate is necessary to initiate and control locomotion and recent data suggest a crucial role for intraspinal neurons in functional recovery following SCI. We aimed to determine whether, in lampreys, axotomized spinal glutamatergic neurons, which lose glutamate immunoreactivity immediately after SCI, recover it later on and to study the long-term evolution and anatomical recovery of the spinal glutamatergic system after SCI. We used glutamate immunoreactivity to study changes in the glutamatergic system, tract-tracing to label axotomized neurons and TUNEL labelling to study cell death. Transections of the cord were made at the level of the fifth gill. TUNEL experiments indicated that cell death is a minor contributor to the initial loss of glutamate immunoreactivity. At least some of the axotomized neurons lose glutamate immunoreactivity, survive and recover glutamate immunoreactivity 1 week post-lesion (wpl). We observed a progressive increase in the number of glutamatergic neurons/processes until an almost complete anatomical recovery at 10 wpl. Among all the glutamatergic populations, the population of cerebrospinal fluid-contacting cells is the only one that never recovers. Our results indicate that full recovery of the glutamatergic system is not necessary for the restoration of function in lampreys. PMID:27886236
Kumar, Hemant; Ropper, Alexander E; Lee, Soo-Hong; Han, Inbo
The blood-spinal cord barrier (BSCB) is a specialized protective barrier that regulates the movement of molecules between blood vessels and the spinal cord parenchyma. Analogous to the blood-brain barrier (BBB), the BSCB plays a crucial role in maintaining the homeostasis and internal environmental stability of the central nervous system (CNS). After spinal cord injury (SCI), BSCB disruption leads to inflammatory cell invasion such as neutrophils and macrophages, contributing to permanent neurological disability. In this review, we focus on the major proteins mediating the BSCB disruption or BSCB repair after SCI. This review is composed of three parts. Section 1. SCI and the BSCB of the review describes critical events involved in the pathophysiology of SCI and their correlation with BSCB integrity/disruption. Section 2. Major proteins involved in BSCB disruption in SCI focuses on the actions of matrix metalloproteinases (MMPs), tumor necrosis factor alpha (TNF-α), heme oxygenase-1 (HO-1), angiopoietins (Angs), bradykinin, nitric oxide (NO), and endothelins (ETs) in BSCB disruption and repair. Section 3. Therapeutic approaches discusses the major therapeutic compounds utilized to date for the prevention of BSCB disruption in animal model of SCI through modulation of several proteins.
Bhatnagar, Tim; Liu, Jie; Yung, Andrew; Cripton, Peter A; Kozlowski, Piotr; Oxland, Thomas
The spinal cord undergoes physical deformation during traumatic spinal cord injury (TSCI), which results in biological damage. This study demonstrates a novel approach, using magnetic resonance imaging and image registration techniques, to quantify the three-dimensional deformation of the cervical spinal cord in an in vivo rat model. Twenty-four male rats were subjected to one of two clinically relevant mechanisms of TSCI (i.e. contusion and dislocation) inside of a MR scanner using a novel apparatus, enabling imaging of the deformed spinal cords. The displacement fields demonstrated qualitative differences between injury mechanisms. Three-dimensional Lagrangian strain fields were calculated, and the results from the contusion injury mechanism were deemed most reliable. Strain field error was assessed using a Monte Carlo approach, which showed that simulated normal strain error experienced a bias, whereas shear strain error did not. In contusion injury, a large region of dorso-ventral compressive strain was observed under the impactor which extended into the ventral region of the spinal cord. High tensile lateral strains under the impactor and compressive lateral strains in the lateral white matter were also observed in contusion. The ability to directly observe and quantify in vivo spinal cord deformation informs our knowledge of the mechanics of TSCI.
Lee, Young Hee; Kong, In Deok; Kim, Sung Hoon; Shinn, Jong Mock; Kim, Jong Heon; Yi, Dongsoo; Lee, Jin Hyeong; Chang, Jae Seung; Kim, Tae-ho; Kim, Eun Ju
Objective To evaluate the cardiopulmonary endurance of subjects with spinal cord injury by measuring the maximal oxygen consumption with varying degrees of spinal cord injury level, age, and regular exercise. Methods We instructed the subjects to perform exercises using arm ergometer on healthy adults at 20 years of age or older with spinal cord injury, and their maximal oxygen consumption (VO2max) was measured with a metabolic measurement system. The exercise proceeded stepwise according to the exercise protocol and was stopped when the subject was exhausted or when VO2 reached an equilibriu Results Among the 40 subjects, there were 10 subjects with cervical cord injury, 27 with thoracic cord injury, and 3 with lumbar cord injury. Twenty-five subjects who were exercised regularly showed statistically higher results of VO2max than those who did not exercise regularly. Subjects with cervical injury showed statistically lower VO2max than the subjects with thoracic or lumbar injury out of the 40 subjects with neurologic injury. In addition, higher age showed a statistically lower VO2max. Lastly, the regularly exercising paraplegic group showed higher VO2max than the non-exercising paraplegic group. Conclusion There are differences in VO2max of subjects with spinal cord injury according to the degree of neurologic injury, age, and whether the subject participates in regular exercise. We found that regular exercise increased the VO2max in individuals with spinal cord injury. PMID:25750877
Krause, James S.
Objectives To identify: (a) the annual incidence of subsequent injury and injury related hospitalizations among individuals with pre-existing spinal cord injury (SCI) and (b) risk and protective behaviors associated with differential risk of injury. Design Longitudinal, mailed survey. Participants were enrolled in 1997-1998, with a follow-up conducted 10 years later. Setting Data were collected from participants identified from a specialty hospital and analyzed at a medical university in the Southeastern United States. Participants There were 1386 participants during the baseline enrollment, 821 of whom also participated in the 10-year follow-up. Inclusion criteria were: (1) traumatic SCI with residual impairment A-D, (2) non-surgical onset, (3) age 18 years or older, and (4) a minimum of 12 months post-SCI. Interventions Main Outcome Measures Number of injuries severe enough to require treatment in a clinic, emergency department, or hospital in the 12 months prior to the survey, and number of injury related hospitalizations. Predictor variables included selected items from the Behavioral Risk Factor Surveillance System, the Zuckerman-Kuhlman Personality Questionnaire, and prescription medication usage. Results Over 23% of participants reported at least 1 injury within the past year, an increase from that reported 10 years earlier by the same participants (19%), and 7% reported at least 1 injury related hospitalization. Those who reported a subsequent injury during the preliminary baseline data collection were about twice as likely to report at least 1 injury 10 years later. Binge drinking, psychotropic prescription medication use, and several personality characteristics were also related to injuries and/or injury hospitalization. Conclusions Risk of injury continues to be a significant concern in the years and decades after SCI onset. Behavioral and personality factors hold the key to prevention. PMID:21044720
Arora, Bhawana; Suresh, Srinivasan
We present a retrospective case series of 15 children (aged 8-16 years) with blunt traumatic spinal cord injury who were treated with methylprednisolone as per the National Acute Spinal Cord Injury Study protocol. Of all patients, 12 (80%) were male. Causes were sports injuries (n = 9), motor vehicle crashes (n = 2), and falls (n = 4). Most injuries were nonskeletal (n = 14), and all patients had incomplete injury of the spinal cord. The most common location of tenderness was cervical (n = 7). Of the 15 patients, methylprednisolone was initiated within 3 hours in 13 patients and between 3 and 8 hours in 2 patients. All patients received the medication for 23 hours as per the National Acute Spinal Cord Injury Study protocol. Of the 15 patients, 13 recovered completely by 24 hours and were discharged with a diagnosis of spinal cord concussion. One patient had compression fracture of T5 and T3-T5 spinal contusion but no long-term neurological deficit. One patient was discharged with diagnosis of C1-C3 spinal cord contusion (by magnetic resonance imaging) and had partial recovery at 2 years after injury. All patients with a diagnosis of cord concussion had normal plain films of the spine and computed tomographic and magnetic resonance imaging findings. None of the patients had any associated major traumatic injuries to other organ systems. The high-dose steroid therapy did not result in any serious bacterial infections.
ABSTRACT A long-standing goal of spinal cord injury research is to develop effective spinal cord repair strategies for the clinic. Rat models of spinal cord injury provide an important mammalian model in which to evaluate treatment strategies and to understand the pathological basis of spinal cord injuries. These models have facilitated the development of robust tests for assessing the recovery of locomotor and sensory functions. Rat models have also allowed us to understand how neuronal circuitry changes following spinal cord injury and how recovery could be promoted by enhancing spontaneous regenerative mechanisms and by counteracting intrinsic inhibitory factors. Rat studies have also revealed possible routes to rescuing circuitry and cells in the acute stage of injury. Spatiotemporal and functional studies in these models highlight the therapeutic potential of manipulating inflammation, scarring and myelination. In addition, potential replacement therapies for spinal cord injury, including grafts and bridges, stem primarily from rat studies. Here, we discuss advantages and disadvantages of rat experimental spinal cord injury models and summarize knowledge gained from these models. We also discuss how an emerging understanding of different forms of injury, their pathology and degree of recovery has inspired numerous treatment strategies, some of which have led to clinical trials. PMID:27736748
Kjell, Jacob; Olson, Lars
A long-standing goal of spinal cord injury research is to develop effective spinal cord repair strategies for the clinic. Rat models of spinal cord injury provide an important mammalian model in which to evaluate treatment strategies and to understand the pathological basis of spinal cord injuries. These models have facilitated the development of robust tests for assessing the recovery of locomotor and sensory functions. Rat models have also allowed us to understand how neuronal circuitry changes following spinal cord injury and how recovery could be promoted by enhancing spontaneous regenerative mechanisms and by counteracting intrinsic inhibitory factors. Rat studies have also revealed possible routes to rescuing circuitry and cells in the acute stage of injury. Spatiotemporal and functional studies in these models highlight the therapeutic potential of manipulating inflammation, scarring and myelination. In addition, potential replacement therapies for spinal cord injury, including grafts and bridges, stem primarily from rat studies. Here, we discuss advantages and disadvantages of rat experimental spinal cord injury models and summarize knowledge gained from these models. We also discuss how an emerging understanding of different forms of injury, their pathology and degree of recovery has inspired numerous treatment strategies, some of which have led to clinical trials.
Strand, Nicholas S; Hoi, Kimberly K; Phan, Tien M T; Ray, Catherine A; Berndt, Jason D; Moon, Randall T
Unlike mammals, zebrafish can regenerate their injured spinal cord and regain control of caudal tissues. It was recently shown that Wnt/β-catenin signaling is necessary for spinal cord regeneration in the larval zebrafish. However, the molecular mechanisms of regeneration may or may not be conserved between larval and adult zebrafish. To test this, we assessed the role of Wnt/β-catenin signaling after spinal cord injury in the adult zebrafish. We show that Wnt/β-catenin signaling is increased after spinal cord injury in the adult zebrafish. Moreover, overexpression of Dkk1b inhibited Wnt/β-catenin signaling in the regenerating spinal cord of adult zebrafish. Dkk1b overexpression also inhibited locomotor recovery, axon regeneration, and glial bridge formation in the injured spinal cord. Thus, our data illustrate a conserved role for Wnt/β-catenin signaling in adult and larval zebrafish spinal cord regeneration.
We have demonstrated no adverse effects of DFA on bladder function following spinal cord injury. However, the drug resulted in no improvement in...We demonstrated that 40 mg/kg DFA is the minimally effective dose to induce L-selectin shedding in a mouse model of spinal cord injury -We...using this paradigm for two injury severities, mild and severe, suggesting a robust therapeutic effect -We identified no adverse effects to animal
Scher, A T
Deliberate crashing of the opposing packs prior to a rugby scrum is an illegal but commonly practised manoeuvre which can lead to abnormal flexion forces being applied to players in the front row, with resultant cervical spine and spinal cord injury. Two cases of cervical spinal cord injury sustained in this manner are presented. The mechanism of injury, the forces involved and preventive measures are discussed.
Gensel, John C; Zhang, Bei
The injured spinal cord does not heal properly. In contrast, tissue repair and functional recovery occur after skin or muscle injuries. The reason for this dichotomy in wound repair is unclear but inflammation, and specifically macrophage activation, likely plays a key role. Macrophages have the ability to promote the repair of injured tissue by regulating transitions through different phase of the healing response. In the current review we compare and contrast the healing and inflammatory responses between spinal cord injuries and tissues that undergo complete wound resolution. Through this comparison, we identify key macrophage phenotypes that are inaptly triggered or absent after spinal cord injury and discuss spinal cord stimuli that contribute to this maladaptive response. Sequential activation of classic, pro-inflammatory, M1 macrophages and alternatively activated, M2a, M2b, and M2c macrophages occurs during normal healing and facilitates transitions through the inflammatory, proliferative, and remodeling phases of repair. In contrast, in the injured spinal cord, pro-inflammatory macrophages potentiate a prolonged inflammatory phase and remodeling is not properly initiated. The desynchronized macrophage activation after spinal cord injury is reminiscent of the inflammation present in chronic, non-healing wounds. By refining the role macrophages play in spinal cord injury repair we bring to light important areas for future neuroinflammation and neurotrauma research. This article is part of a Special Issue entitled SI: Spinal cord injury.
White-Schenk, Désirée.; Shi, Riyi; Leary, James F.
An estimated 12,000 new cases of spinal cord injury (SCI) occur every year in the United States. A small oxidative molecule responsible for secondary injury, acrolein, is an important target in SCI. Acrolein attacks essential proteins and lipids, creating a feed-forward loop of oxidative stress in both the primary injury area and the surrounding areas. A small molecule used and FDA-approved for hypertension, hydralazine, has been found to "scavenge" acrolein after injury, but its delivery and short half-life, as well as its hypertension effects, hinder its application for SCI. Nanomedical systems broaden the range of therapeutic availability and efficacy over conventional medicine. They allow for targeted delivery of therapeutic molecules to tissues of interest, reducing side effects of untargeted therapies in unwanted areas. Nanoparticles made from silica form porous networks that can carry therapeutic molecules throughout the body. To attenuate the acrolein cascade and improve therapeutic availability, we have used a one-step, modified Stober method to synthesize two types of silica nanoparticles. Both particles are "stealth-coated" with poly(ethylene) glycol (PEG) (to minimize interactions with the immune system and to increase circulation time), which is also a therapeutic agent for SCI by facilitating membrane repair. One nanoparticle type contains an amine-terminal PEG (SiNP-mPEG-Am) and the other possesses a terminal hydrazide group (SiNP-mPEG-Hz). The former allows for exploration of hydralazine delivery, loading, and controlled release. The latter group has the ability to react with acrolein, allowing the nanoparticle to scavenge directly. The nanoparticles have been characterized and are being explored using neuronal PC-12 cells in vitro, demonstrating the potential of novel silica nanoparticles for use in attenuating secondary injury after SCI.
Laclaustra, Martin; Van Den Berg, Elizabeth Louise Maayken; Hurtado-Roca, Yamilée; Castellote, Juan Manuel
Background and Aims Few large studies have examined the relationship between spinal cord injury (SCI) and lipid profile. We studied serum lipid concentrations in subjects with traumatic SCI in relation to the degree of neurological involvement and time since injury, and compared them with values from a reference sample for the Spanish population (DRECE study). Materials and Methods A retrospective cohort was built from 177 consecutive cases with traumatic SCI admitted to the SCI unit of the Miguel Servet Hospital in Aragon (Spain). Outcome measures (cholesterol, triglycerides, HDL-c and LDL-c levels) were analyzed according to the ASIA Impairment Scale (AIS), neurological level of injury (involvement of all limbs vs. only lower limbs), and time since injury. All analyses were adjusted for age and sex. Results Cases without preserved motor function (AIS A or B) had lower total and HDL cholesterol than the others (-11.4 [-21.5, -1.4] mg/dL total cholesterol and -5.1 [-8.8, -1.4] mg/dL HDL-c), and cases with all-limb involvement had lower total, HDL, and LDL cholesterol than those with only lower-limb involvement (-14.0 [-24.6, -3.4] mg/dL total cholesterol, -4.1 [-8.0, -0.2] mg/dL HDL-c, and -10.0 [-19.7, -0.3] mg/dL LDL-c) (all p<0.05). No association was found between lipid concentrations and time since injury. Concentrations of lipid subfractions and triglycerides in SCI subjects were lower than in sex- and age-stratified values from the reference sample. Conclusion A high degree of neurological involvement in SCI (anatomically higher lesions and AIS A or B) is associated with lower total cholesterol and HDL-c. PMID:25706982
Contreras-Vidal, Jose L.; Bhagat, Nikunj A.; Brantley, Justin; Cruz-Garza, Jesus G.; He, Yongtian; Manley, Quinn; Nakagome, Sho; Nathan, Kevin; Tan, Su H.; Zhu, Fangshi; Pons, Jose L.
Objective. Powered exoskeletons promise to increase the quality of life of people with lower-body paralysis or weakened legs by assisting or restoring legged mobility while providing health benefits across multiple physiological systems. Here, a systematic review of the literature on powered exoskeletons addressed critical questions: What is the current evidence of clinical efficacy for lower-limb powered exoskeletons? What are the benefits and risks for individuals with spinal cord injury (SCI)? What are the levels of injury considered in such studies? What are their outcome measures? What are the opportunities for the next generation exoskeletons? Approach. A systematic search of online databases was performed to identify clinical trials and safety or efficacy studies with lower-limb powered exoskeletons for individuals with SCI. Twenty-two studies with eight powered exoskeletons thus selected, were analyzed based on the protocol design, subject demographics, study duration, and primary/secondary outcome measures for assessing exoskeleton's performance in SCI subjects. Main results. Findings show that the level of injury varies across studies, with T10 injuries being represented in 45.4% of the studies. A categorical breakdown of outcome measures revealed 63% of these measures were gait and ambulation related, followed by energy expenditure (16%), physiological improvements (13%), and usability and comfort (8%). Moreover, outcome measures varied across studies, and none had measures spanning every category, making comparisons difficult. Significance. This review of the literature shows that a majority of current studies focus on thoracic level injury as well as there is an emphasis on ambulatory-related primary outcome measures. Future research should: 1) develop criteria for optimal selection and training of patients most likely to benefit from this technology, 2) design multimodal gait intention detection systems that engage and empower the user, 3) develop
Gorzkowski, Julie; Kelly, Erin H.; Klaas, Sara J.; Vogel, Lawrence C.
Objective Examine caregiver-report of obstacles to community participation for youth with spinal cord injury (SCI), and explore relationships between obstacles and child, caregiver, and community characteristics. Design Two hundred and one primary caregivers of youth with SCI ages 7–17 years were interviewed at three pediatric SCI centers within a single-hospital system. Caregivers answered an open-ended question assessing obstacles to youth participation. A mixed-methods approach was incorporated, where qualitative methods analyzed caregiver-reported obstacles, and exploratory multivariate analyses examined relationships between obstacles and demographic variables. Results Caregivers were primarily mothers (74%), married (69%), employed (54%), had college experience (67%), and lived in small towns (55%). Youths' mean age was 12.60 years at interview and 7.19 years at injury, 70% had paraplegia, and 55% had complete injuries. Analyses revealed that youth participation was limited by obstacles across six domains: community, disability-related, practical concerns, child-internal, social, and other. Child, caregiver, and community characteristics were related to overall report of obstacles, and report of community obstacles, disability-related obstacles, and practical concerns. Caregiver college experience and small town living predicted overall report of obstacles. Having a child injured at a younger age, caregiver college experience, and small town living predicted community obstacles. Having a child with an incomplete injury and recent medical complication predicted disability-related obstacles. Caregiver employment predicted practical concerns. Conclusion Youth from small towns, those injured younger, those with incomplete injuries, and those experiencing recent medical complications may need additional supports and resources to maximize participation. Clinicians should work with caregivers to identify and problem-solve obstacles to youth participation. PMID
Taylor-Schroeder, Sally; LaBarbera, Jacqueline; McDowell, Shari; Zanca, Jeanne M.; Natale, Audrey; Mumma, Sherry; Gassaway, Julie; Backus, Deborah
Background/objective To describe the nature and distribution of activities during physical therapy (PT) delivered in inpatient spinal cord injury (SCI) rehabilitation and discuss predictors (patient and injury characteristics) of the amount of time spent in PT for specific treatment activities. Methods Six hundred patients from six inpatient SCI centers were enrolled in the SCIRehab study. Physical therapists documented details, including time spent, of treatment provided during 37 306 PT sessions that occurred during inpatient SCI rehabilitation. Ordinary least squares regression models associated patient and injury characteristics with time spent in specific PT activities. Results SCIRehab patients received a mean total of 55.3 hours of PT over the course of their rehabilitation stay. Significant differences among four neurologic groups were seen in the amount of time spent on most activities, including the most common PT activities of strengthening exercises, stretching, transfer training, wheelchair mobility training, and gait training. Most PT work (77%) was provided in individual therapy sessions; the remaining 23% was done in group settings. Patient and injury characteristics explained only some of the variations seen in time spent on wheelchair mobility, transfer and bed mobility training, and range of motion/stretching. Conclusion Analysis yielded both expected and unexpected trends in SCI rehabilitation. Significant variation was seen in time spent on PT activities within and among injury groups. Providing therapeutic strengthening treatments consumed the greatest proportion of PT time. About one-quarter of all PT services were provided in group settings. Details about services provided, including time spent, will serve as a starting point in detailing the optimal treatment delivery for maximal outcomes. PMID:21675354
Zhang, Peixun; Zhang, Luping; Zhu, Lei; Chen, Fangmin; Zhou, Shuai; Tian, Ting; Zhang, Yuqiang; Jiang, Xiaorui; Li, Xuekun; Zhang, Chuansen; Xu, Lin; Huang, Fei
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
Zhao, Liang; Jing, Yu; Qu, Lin; Meng, Xiangwei; Cao, Yang; Tan, Huibing
The expression of adrenomedullin (ADM) in injured tissue of rat spinal cord was observed and the effect of recombinant human erythropoietin was analyzed. A total of 45 Sprague-Dawley rats were selected and divided into 3 equal groups including, a sham-operation group in which rats received an excision of vertebral plate; a spinal cord injury model group and a recombinant human erythropoietin group in which rats with spinal cord injury received a caudal vein injection of 300 units recombinant human erythropoietin after injury. Hematoxylin and eosin staining was performed to observe the spinal cord injury conditions. Immunohistochemical staining was performed to observe the expression of ADM. Pathologic changes in the group of recombinant human erythropoietin at various times were significantly less severe than those in the group of spinal cord injury model. The expression of ADM was increased particularly in the group of recombinant human erythropoietin (P<0.01). The improved Tarlov scores of the group of spinal cord injury model and the group of recombinant human erythropoietin were lower than those of the sham-operation group at 3, 6 and 9 days (P<0.01). Thus, the recombinant human erythropoietin is capable of alleviating the secondary injury of spinal cord. One of the mechanisms may be achieved by promoting the increase of ADM expression.
Zhao, Liang; Jing, Yu; Qu, Lin; Meng, Xiangwei; Cao, Yang; Tan, Huibing
The expression of adrenomedullin (ADM) in injured tissue of rat spinal cord was observed and the effect of recombinant human erythropoietin was analyzed. A total of 45 Sprague-Dawley rats were selected and divided into 3 equal groups including, a sham-operation group in which rats received an excision of vertebral plate; a spinal cord injury model group and a recombinant human erythropoietin group in which rats with spinal cord injury received a caudal vein injection of 300 units recombinant human erythropoietin after injury. Hematoxylin and eosin staining was performed to observe the spinal cord injury conditions. Immunohistochemical staining was performed to observe the expression of ADM. Pathologic changes in the group of recombinant human erythropoietin at various times were significantly less severe than those in the group of spinal cord injury model. The expression of ADM was increased particularly in the group of recombinant human erythropoietin (P<0.01). The improved Tarlov scores of the group of spinal cord injury model and the group of recombinant human erythropoietin were lower than those of the sham-operation group at 3, 6 and 9 days (P<0.01). Thus, the recombinant human erythropoietin is capable of alleviating the secondary injury of spinal cord. One of the mechanisms may be achieved by promoting the increase of ADM expression. PMID:28101163
O’Brien, Laura C; Gorgey, Ashraf S
Mitochondria are the main source of cellular energy production and are dynamic organelles that undergo biogenesis, remodeling, and degradation. Mitochondrial dysfunction is observed in a number of disease states including acute and chronic central or peripheral nervous system injury by traumatic brain injury, spinal cord injury (SCI), and neurodegenerative disease as well as in metabolic disturbances such as insulin resistance, type II diabetes and obesity. Mitochondrial dysfunction is most commonly observed in high energy requiring tissues like the brain and skeletal muscle. In persons with chronic SCI, changes to skeletal muscle may include remarkable atrophy and conversion of muscle fiber type from oxidative to fast glycolytic, combined with increased infiltration of intramuscular adipose tissue. These changes contribute to a proinflammatory environment, glucose intolerance and insulin resistance. The loss of metabolically active muscle combined with inactivity predisposes individuals with SCI to type II diabetes and obesity. The contribution of skeletal muscle mitochondrial density and electron transport chain activity to the development of the aforementioned comorbidities following SCI is unclear. A better understanding of the mechanisms involved in skeletal muscle mitochondrial dynamics is imperative to designing and testing effective treatments for this growing population. The current editorial will review ways to study mitochondrial function and the importance of improving skeletal muscle mitochondrial health in clinical populations with a special focus on chronic SCI. PMID:27795944
Lusilla-Palacios, P; Castellano-Tejedor, Carmina
The objective of this study was to review recent findings about the prevalence of substance use (SU) and substance use disorders (SUD), and to discuss the related impact on health in spinal cord injury (SCI) population. For this purpose, computer-aided searches of MEDLINE (PubMed) and the Cochrane Library were conducted. From an initial pool of 59 articles, 52 met the inclusion criteria. Most of the studies referred to alcohol and tobacco and only a few studies reported on other substances. Study designs were mainly cross-sectional and descriptive, with scarce intervention and longitudinal studies. Although a high prevalence of post-injury SU has been documented among SCI patients, limited research exists on pre-injury SU and on longitudinal studies. Moreover, when exploring SUD, it has not been systematically studied in accordance with CIE or DSM criteria. Alcohol appears to be the most consumed substance among this population. Additionally, those patients with SU have shown poorer outcomes in different health indicators. Therefore, more insight is required to increase scientific knowledge in this field and to recommend tailored preventive interventions and research priorities in relation to this population.
Zheng, Weimin; Chen, Qian; Chen, Xin; Wan, Lu; Qin, Wen; Qi, Zhigang; Li, Kuncheng
It remains unknown whether spinal cord injury (SCI) could indirectly impair or reshape the white matter (WM) of human brain and whether these changes are correlated with injury severity, duration, or clinical performance. We choose tract-based spatial statistics (TBSS) to investigate the possible changes in whole-brain white matter integrity and their associations with clinical variables in fifteen patients with SCI. Compared with the healthy controls, the patients exhibited significant decreases in WM fractional anisotropy (FA) in the left angular gyrus (AG), right cerebellum (CB), left precentral gyrus (PreCG), left lateral occipital region (LOC), left superior longitudinal fasciculus (SLF), left supramarginal gyrus (SMG), and left postcentral gyrus (PostCG) (p < 0.01, TFCE corrected). No significant differences were found in all diffusion indices between the complete and incomplete SCI. However, significantly negative correlation was shown between the increased radial diffusivity (RD) of left AG and total motor scores (uncorrected p < 0.05). Our findings provide evidence that SCI can cause not only direct degeneration but also transneuronal degeneration of brain WM, and these changes may be irrespective of the injury severity. The affection of left AG on rehabilitation therapies need to be further researched in the future. PMID:28255458
Mehrabi, Soraya; Eftekhari, Sanaz; Moradi, Fateme; Delaviz, Hamdollah; Pourheidar, Bagher; Azizi, Monir; Zendehdel, Adib; Shahbazi, Ali; Joghataei, Mohammad Taghi
Spinal cord injury (SCI) is a debilitating disease which leads to progressive functional damages. Because of limited axonal regeneration in the central nervous system, there is no or little recovery expected in the patients. Different cellular and molecular approaches were investigated in SCI animal models. Cellular transplantation of stem cells can potentially replace damaged tissue and provide a suitable microenvironment for axons to regenerate. Here, we reviewed the last approaches applied by our colleagues and others in order to improve axonal regeneration following SCI. We used different types of stem cells via different methods. First, fetal olfactory mucosa, schwann, and bone marrow stromal cells were transplanted into the injury sites in SCI models. In later studies, was applied simultaneous transplantation of stem cells with chondroitinase ABC in SCI models with the aid of nanoparticles. Using these approaches, considerable functional recovery was observed. However, considering some challenges in stem cell therapy such as rejection, infection, and development of a new cancer, our more recent strategy was application of cytokines. We observed a significant improvement in motor function of rats when stromal derived factor-1 was used to attract innate stem cells to the injury site. In conclusion, it seems that co-transplantation of different cells accompanies with other factors like enzymes and growth factors via new delivery systems may yield better results in SCI. PMID:25337345
Lukovic, Dunja; Moreno-Manzano, Victoria; Lopez-Mocholi, Eric; Rodriguez-Jiménez, Francisco Javier; Jendelova, Pavla; Sykova, Eva; Oria, Marc; Stojkovic, Miodrag; Erceg, Slaven
Spinal cord injury (SCI) results in neural loss and consequently motor and sensory impairment below the injury. There are currently no effective therapies for the treatment of traumatic SCI in humans. Various animal models have been developed to mimic human SCI. Widely used animal models of SCI are complete or partial transection or experimental contusion and compression, with both bearing controversy as to which one more appropriately reproduces the human SCI functional consequences. Here we present in details the widely used procedure of complete spinal cord transection as a faithful animal model to investigate neural and functional repair of the damaged tissue by exogenous human transplanted cells. This injury model offers the advantage of complete damage to a spinal cord at a defined place and time, is relatively simple to standardize and is highly reproducible. PMID:25860664
Wang, Peng; Huang, Lin; Tang, Yong; Wang, Wenhao; Chen, Keng; Ye, Jichao; Lu, Ciyong; Wu, Yanfeng; Shen, Huiyong
Background Spinal cord injuries are highly disabling and deadly injuries. Currently, few studies focus on non-traumatic spinal cord injuries, and there is little information regarding the risk factors for complete injuries. This study aims to describe the demographics and the injury characteristics for both traumatic and non-traumatic spinal cord injuries and to explore the risk factors for complete spinal cord injuries. Methods A retrospective study was performed by reviewing the medical records of 3,832 patients with spinal cord injuries who were first admitted to the sampled hospitals in Guangdong, China. The demographics and injury characteristics of the patients were described and compared between the different groups using the chi-square test. Logistic regression was conducted to analyze the risk factors for complete spinal cord injuries. Results The proportion of patients increased from 7.0% to 14.0% from 2003 to 2011. The male-to-female ratio was 3.0∶1. The major cause of spinal cord injuries was traffic accidents (21.7%). Many of the injured were workers (36.2%), peasants (22.8%), and unemployed people (13.9%); these occupations accounted for 72.9% of the total sample. A multivariate logistic regression model revealed that the OR (95% CI) for male gender compared to female gender was 1.25 (1.07–1.89), the OR (95%CI) for having a spinal fracture was 1.56 (1.35–2.60), the OR (95%CI) for having a thoracic injury was 1.23 (1.10–2.00), and the OR (95%CI) for having complications was 2.47 (1.96–3.13). Conclusion The proportion of males was higher than the proportion of females. Workers, peasants and the unemployed comprised the high-risk occupational categories. Male gender, having a spinal fracture, having a thoracic injury, and having complications were the major risk factors for a complete injury. We recommend that preventive measures should focus on high-risk populations, such as young males. PMID:24489652
Takeoka, Aya; Vollenweider, Isabel; Courtine, Grégoire; Arber, Silvia
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.
De Berdt, P; Vanacker, J; Ucakar, B; Elens, L; Diogenes, A; Leprince, J G; Deumens, R; des Rieux, A
Stem cells of the apical papilla (SCAP) represent great promise regarding treatment of neural tissue damage, such as spinal cord injury (SCI). They derive from the neural crest, express numerous neurogenic markers, and mediate neurite outgrowth and axonal targeting. The goal of the present work was to investigate for the first time their potential to promote motor recovery after SCI in a rat hemisection model when delivered in their original stem cell niche-that is, by transplantation of the human apical papilla tissue itself into the lesion. Control groups consisted of animals subjected to laminectomy only (shams) and to lesion either untreated or injected with a fibrin hydrogel with or without human SCAP. Basso-Beattie-Bresnahan locomotor scores at 1 and 3 d postsurgery confirmed early functional decline in all SCI groups. This significant impairment was reversed, as seen in CatWalk analyses, after transplantation of apical papilla into the injured spinal cord wound, whereas the other groups demonstrated persistent functional impairment. Moreover, tactile allodynia did not develop as an unwanted side effect in any of the groups, even though the SCAP hydrogel group showed higher expression of the microglial marker Iba-1, which has been frequently associated with allodynia. Notably, the apical papilla transplant group presented with reduced Iba-1 expression level. Masson trichrome and human mitochondria staining showed the preservation of the apical papilla integrity and the presence of numerous human cells, while human cells could no longer be detected in the SCAP hydrogel group at the 6-wk postsurgery time point. Altogether, our data suggest that the transplantation of a human apical papilla at the lesion site improves gait in spinally injured rats and reduces glial reactivity. It also underlines the potential interest for the application of delivering SCAP in their original niche, as compared with use of a fibrin hydrogel.
toward the lumbar spine. Three hundred and nineteen (15%) of the 2101 injuries occurred in the cervical spine, while 591 (28%) were located in the...with spinal injuries solely to the cervical spine, four (24%) with injuries to the lumbar region, and one with an isolated thoracic spine injury. Fig. 1...fractures were reported in 3% of patients each, and there were ten documented flexion -distraction injuries and two fracture- dislocations. One hundred
Audigé, Laurent; Hanson, Beate; Chapman, Jens R.; Hosman, Allard J. F.
Since Böhler published the first categorization of spinal injuries based on plain radiographic examinations in 1929, numerous classifications have been proposed. Despite all these efforts, however, only a few have been tested for reliability and validity. This methodological, conceptual review summarizes that a spinal injury classification system should be clinically relevant, reliable and accurate. The clinical relevance of a classification is directly related to its content validity. The ideal content of a spinal injury classification should only include injury characteristics of the vertebral column, is primarily based on the increasingly routinely performed CT imaging, and is clearly distinctive from severity scales and treatment algorithms. Clearly defined observation and conversion criteria are crucial determinants of classification systems’ reliability and accuracy. Ideally, two principle spinal injury characteristics should be easy to discern on diagnostic images: the specific location and morphology of the injured spinal structure. Given the current evidence and diagnostic imaging technology, descriptions of the mechanisms of injury and ligamentous injury should not be included in a spinal injury classification. The presence of concomitant neurologic deficits can be integrated in a spinal injury severity scale, which in turn can be considered in a spinal injury treatment algorithm. Ideally, a validation pathway of a spinal injury classification system should be completed prior to its clinical and scientific implementation. This review provides a methodological concept which might be considered prior to the synthesis of new or modified spinal injury classifications. PMID:20464432
Kallakuri, Srinivasu; Purkait, Heena S.; Dalavayi, Satya; VandeVord, Pamela; Cavanaugh, John M.
Introduction: Blast induced neurotrauma has been the signature wound in returning soldiers from the ongoing wars in Iraq and Afghanistan. Of importance is understanding the pathomechansim(s) of blast overpressure (OP) induced axonal injury. Although several recent animal models of blast injury indicate the neuronal and axonal injury in various brain regions, animal studies related to axonal injury in the white matter (WM) tracts of cervical spinal cord are limited. Objective: The purpose of this study was to assess the extent of axonal injury in WM tracts of cervical spinal cord in male Sprague Dawley rats subjected to a single insult of blast OP. Materials and Methods: Sagittal brainstem sections and horizontal cervical spinal cord sections from blast and sham animals were stained by neurofilament light (NF-L) chain and beta amyloid precursor protein immunocytochemistry and observed for axonal injury changes. Results: Observations from this preliminary study demonstrate axonal injury changes in the form of prominent swellings, retraction bulbs, and putative signs of membrane disruptions in the brainstem and cervical spinal cord WM tracts of rats subjected to blast OP. Conclusions: Prominent axonal injury changes following the blast OP exposure in brainstem and cervical spinal WM tracts underscores the need for careful evaluation of blast induced injury changes and associated symptoms. NF-L immunocytochemistry can be considered as an additional tool to assess the blast OP induced axonal injury. PMID:26752889
Zhou, Kaisheng; Nan, Wei; Feng, Dongliang; Yi, Zhigang; Zhu, Yandong; Long, Zaiyun; Li, Sen; Zhang, Haihong; Wu, Yamin
Ski is an evolutionarily conserved protein and widely participates in the regulation of various pathological and physiological processes such as wound healing, liver regeneration, development of the embryonic nervous system, muscle differentiation, and progression of many kinds of tumors. However, the distribution and function of Ski in central nervous system lesion and disease remain unclear. In this study, we investigated the spatiotemporal expression of Ski in a spinal cord injury (SCI) model in adult rats. Western Blot analysis indicated that Ski was expressed in both normal and injured spinal cord, and showed a significant upregulation after SCI compared with the sham group. Double-labeled immunofluorescence staining showed that Ski was significantly expressed in astrocytes, but not in the neurons. Western Blot analyses of glial fibrillary acidic protein (GFAP) and BBB scores were carried out and correlation analysis showed a positive correlation between them. In addition, the relative expression level of Ski was also positively correlated with the relative expression level of GFAP. Moreover, the conspicuous co-expression band of Ski and GFAP at the lesion border was found in the results of immunofluorescence staining combined with the pattern of glial scar formation reflected by H&E staining; in addition, it was found that Ski was also highly associated with glial scar. On the basis of our data, we speculated that Ski might play an important role in the process of reactive astrogliosis after SCI and our study might provide a basis for further study on the detailed role of Ski in astrocytes.
Chu, Tianci; Zhou, Hengxing; Li, Fuyuan; Wang, Tianyi; Lu, Lu; Feng, Shiqing
Spinal cord injury (SCI) often causes incurable neurological dysfunction because axonal regeneration in adult spinal cord is rare. Astrocytes are gradually recognized as being necessary for the regeneration after SCI as they promote axonal growth under both physiological and pathophysiological conditions. Heterogeneous populations of astrocytes have been explored for structural and functional restoration. The results range from the early variable and modest effects of immature astrocyte transplantation to the later significant, but controversial, outcomes of glial-restricted precursor (GRP)-derived astrocyte (GDA) transplantation. However, the traditional neuron-centric view and the concerns about the inhibitory roles of astrocytes after SCI, along with the sporadic studies and the lack of a comprehensive review, have led to some confusion over the usefulness of astrocytes in SCI. It is the purpose of the review to discuss the current status of astrocyte transplantation for SCI based on a dialectical view of the context-dependent manner of astrocyte behavior and the time-associated characteristics of glial scarring. Critical issues are then analyzed to reveal the potential direction of future research.
Bowers, Christian A; Kundu, Bornali; Hawryluk, Gregory W J
Following publication of NASCIS II, methylprednisolone sodium succinate (MPSS) was hailed as a breakthrough for patients with acute spinal cord injury (SCI). MPSS use for SCI has since become very controversial and it is our opinion that additional evidence is unlikely to break the stalemate amongst clinicians. Patient opinion has the potential to break this stalemate and we review our recent findings which reported that spinal cord injured patients informed of the risks and benefits of MPSS reported a preference for MPSS administration. We discuss the implications of the current MPSS debate on translational research and seek to address some misconceptions which have evolved. As science has failed to resolve the MPSS debate we argue that the debate is an increasingly philosophical one. We question whether SCI might be viewed as a serious condition like cancer where serious side effects of therapeutics are tolerated even when benefits may be small. We also draw attention to the similarity between the side effects of MPSS and isotretinoin which is prescribed for the cosmetic disorder acne vulgaris. Ultimately we question how patient autonomy should be weighed in the context of current SCI guidelines and MPSS's status as a historical standard of care.
Background: Mobility is an important aspect of the rehabilitation of children with spinal cord injury (SCI), is a necessary component of life, and is critical in a child’s development. Depending upon the individual’s age and degree of neurological impairment, the nature of mobility may vary. Objectives: The objective of this article is to establish recommendations surrounding the selection of mobility for children with SCI. Methods: Extensive literature review and multidisciplinary peer review. Results: Types of mobility including power, manual, upright, and community are discussed, and recommendations are made based on medical necessity, neurological level, ASIA Impairment Scale score, and developmental considerations and challenges. Conclusion: Mobility is critical for proper development to occur in the pediatric population, and it may be challenging to make recommendations for mobility in children with SCI. It is essential for clinicians providing care to children with SCI to address mobility in a comprehensive and longitudinal manner across the children’s environments. PMID:23671384
Collinger, Jennifer L.; Foldes, Stephen; Bruns, Tim M.; Wodlinger, Brian; Gaunt, Robert; Weber, Douglas J.
Context Spinal cord injury (SCI) results in a loss of function and sensation below the level of the lesion. Neuroprosthetic technology has been developed to help restore motor and autonomic functions as well as to provide sensory feedback. Findings This paper provides an overview of neuroprosthetic technology that aims to address the priorities for functional restoration as defined by individuals with SCI. We describe neuroprostheses that are in various stages of preclinical development, clinical testing, and commercialization including functional electrical stimulators, epidural and intraspinal microstimulation, bladder neuroprosthesis, and cortical stimulation for restoring sensation. We also discuss neural recording technologies that may provide command or feedback signals for neuroprosthetic devices. Conclusion/clinical relevance Neuroprostheses have begun to address the priorities of individuals with SCI, although there remains room for improvement. In addition to continued technological improvements, closing the loop between the technology and the user may help provide intuitive device control with high levels of performance. PMID:23820142
Bach, John R.
This article describes noninvasive acute and long-term management of the respiratory muscle paralysis of high spinal cord injury (SCI). This includes full-setting, continuous ventilatory support by noninvasive intermittent positive pressure ventilation (NIV) to support inspiratory muscles and mechanically assisted coughing (MAC) to support inspiratory and expiratory muscles. The NIV and MAC can also be used to extubate or decannulate ‘unweanable’ patients with SCI, to prevent intercurrent respiratory tract infections from developing into pneumonia and acute respiratory failure (ARF), and to eliminate tracheostomy and resort to costly electrophrenic/diaphragm pacing (EPP/DP) for most ventilator users, while permitting glossopharyngeal breathing (GPB) for security in the event of ventilator failure. PMID:22525322
Nabbout, Philippe; Slobodov, Gennady; Culkin, Daniel J
Urolithiasis is a common condition in patients with spinal cord injury (SCI). Surgical management of stones in this population is more challenging and associated with lower clearance rates than the general population. The rate of complications - specifically infectious complications - is also high due to the chronic bacterial colonization. Shock wave lithotripsy (SWL) has a low clearance rate of 44-73 %. Percutaneous nephrolithotripsy is indicated for larger nephrolithiasis, but multiple procedures may be required to clear the stones. Ureteroscopy has been associated with low success rates because of difficulty in obtaining ureteral access. Historically, bladder stones were managed with open surgery or SWL. Recently, good results have been reported with the combination of endoscopic and laparoscopic techniques. Surgical management of urolithiasis in patients with SCI should be performed in high-volume centers in light of the technical challenges and higher rate of perioperative complications.
Nogueira, Paula Cristina; Rabeh, Soraia Assad Nasbine; Caliri, Maria Helena Larcher; Haas, Vanderlei José
A sectional study that had as its objectives to assess caregiver burden of for caregivers of individuals with Traumatic Spinal Cord Injury (TSCI) and its association with sociodemographic variables (age and sex), health status (self-reported illnesses) and caregiver characteristics (care time in years and daily hours of care). Data were collected by consultation of patient files and individual interviews at home using the instrument, Caregiver Burden Scale (CBScale). The results showed that most burden occurred in the domains: environment, disappointment and general strain. Presenting health problem (for all domains of the CBScale) and spending more hours per day in care (in the domain disappointment) represented the variables associated with burden. Studies of a more confirmatory nature than exploratory between the variables studied can be used to measure the burden obtained in this population of caregivers of individuals with TSCI.
Albert, T; Beuret Blanquart, F; Le Chapelain, L; Fattal, C; Goossens, D; Rome, J; Yelnik, A P; Perrouin Verbe, B
This document is part of a series of documents designed by the French Physical and Rehabilitation Medicine Society (SOFMER) and the French Federation of PRM (FEDMER). These documents describe the needs for or a specific type of patients; PRM care objectives, human and material resources to be implemented, chronology as well as expected outcomes. "Care pathways in PRM" is a short document designed to enable the reader (physicians, decision-maker, administrator, lawyer or finance manager) to quickly apprehend the needs of these patients and the available therapeutic care structures for proper organization and pricing of these activities. The patients after spinal cord injury are divided into five categories according to the severity of the impairments, each one being treated according to the same six parameters according to the International Classification of Functioning, Disability and Health (WHO), while taking into account personal and environmental factors that could influence the needs of these patients.
Bach, John R
This article describes noninvasive acute and long-term management of the respiratory muscle paralysis of high spinal cord injury (SCI). This includes full-setting, continuous ventilatory support by noninvasive intermittent positive pressure ventilation (NIV) to support inspiratory muscles and mechanically assisted coughing (MAC) to support inspiratory and expiratory muscles. The NIV and MAC can also be used to extubate or decannulate 'unweanable' patients with SCI, to prevent intercurrent respiratory tract infections from developing into pneumonia and acute respiratory failure (ARF), and to eliminate tracheostomy and resort to costly electrophrenic/diaphragm pacing (EPP/DP) for most ventilator users, while permitting glossopharyngeal breathing (GPB) for security in the event of ventilator failure.
Masuda, Takahiro; Wakahara, Kazuhiko; Matsumoto, Kazu; Hioki, Akira; Shimokawa, Tetsuya; Shimizu, Katsuji; Ogura, Shinji; Akiyama, Haruhiko
Study Design Retrospective study. Purpose To assess treatment outcomes of snowboarding-related spinal and spinal cord injuries. Overview of Literature Snowboarding-related spinal or spinal cord injury have a great impact on social and sporting activities. Methods A retrospective review of 19 cases of surgically treated snowboard-related injury was done. Analyzed parameters included site of injury, type of fracture, peri- and postoperative complications, pre- and postoperative neurological status, activities of daily living, and participation in sports activities at the final follow-up. Results The major site of injury was the thoracolumbar junction caused by fracture-dislocation (13/19 cases). The remaining 6 cases had cervical spine injuries. Over 60% of the patients had Frankel A and B paralysis. All patients were surgically treated by posterior fusion with instrumentation. Five underwent additional anterior fusion. Surgical outcome was restoration of ambulatory capacity in 12 patients (63.2%). Ultimately, 15 patients (78.9%) could return to work. Patients with complete paralysis upon admission showed reduced ambulatory capacity compared to those with incomplete paralysis. None of the patients again participated in any sports activities, including snowboarding. Conclusions Snowboarding-related spinal or spinal cord injury has a great impact on social as well as sports activities. It is necessary to enhance promotion of injury prevention emphasizing the snowboarders' responsibility code. PMID:25705340
Barman, Apurba; Sinha, Mithilesh K; Rao, P Bhaskar
Autonomic dysreflexia is a medical emergency in spinal cord injury. Majority of cases of autonomic dysreflexia are known to be induced by either bladder or bowel distension. Very few cases of recurrent postural autonomic dysreflexia, due to secondary spinal pathology, have been reported. Discovertebral or Andersson lesion, a recognized complication in Ankylosing Spondylitis, can give rise to similar kind of recurrent postural dysreflexic symptoms. Here, we report a case of Ankylosing Spondylitis with high level, complete spinal cord injury, where the patient was developing recurrent postural autonomic dysreflexia and its successful management. Andersson lesion in the lumbar spine below the level of injury was demonstrated in this case report.
The incidence of spinal cord injury in thoracic endovascular aortic repair (TEVAR) has been 3-5 % from recent major papers where sacrifice of the critical intercostal arteries is inevitable by a stent graft. Hemodynamic stability, which depends on a network of blood vessels around the cord is most important not only during but also after stent-graft deployment. High risk factors of spinal cord injury during endovascular aortic repair are (1) coverage of the left subclavian artery, (2) extensive coverage of long segments of the thoracic aorta, (3) prior downstream aortic repair, (4) compromising important intercostal (T8-L1), vertebral, pelvic and hypogastric collaterals, and (5) shaggy aorta. Preoperative, intraoperative, and postoperative managements have been required to prevent spinal cord injury with TEVAR. For imaging assessment of blood supply to spinal cord including Adamkiewicz artery, prophylactic cerebrospinal fluid drainage is mandatory, and monitoring motor-evoked potential is recommended for high risk factors of spinal cord injury. Mean arterial pressure should be maintained over 90 mmHg after stent-graft placement for a while to prevent delayed spinal cord ischemia in high-risk patients of spinal cord ischemia. Finally, because spinal cord injury during TEVAR is not rare and negligible, perioperative care during TEVAR should be strictly performed according to the protocol proposed by each cardiovascular team.
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; Schwab, Jan M
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.
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
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
Holly, Langston T.; Blaskiewicz, Donald; Wu, Aiguo; Feng, Cameron; Ying, Zhe; Gomez-Pinilla, Fernando
Object The pathogenesis of cervical spondylotic myelopathy (CSM) is related to both primary mechanical and secondary biological injury. The authors of this study explored a novel, noninvasive method of promoting neuroprotection in myelopathy by using curcumin to minimize oxidative cellular injury and the capacity of omega-3 fatty acids to support membrane structure and improve neurotransmission. Methods An animal model of CSM was created using a nonresorbable expandable polymer placed in the thoracic epidural space, which induced delayed myelopathy. Animals that underwent placement of the expandable polymer were exposed to either a diet rich in docosahexaenoic acid and curcumin (DHA-Cur) or a standard Western diet (WD). Twenty-seven animals underwent serial gait testing, and spinal cord molecular assessments were performed after the 6-week study period. Results At the conclusion of the study period, gait analysis revealed significantly worse function in the WD group than in the DHA-Cur group. Levels of brain-derived neurotrophic factor (BDNF), syntaxin-3, and 4-hydroxynonenal (4-HNE) were measured in the thoracic region affected by compression and lumbar enlargement. Results showed that BDNF levels in the DHA-Cur group were not significantly different from those in the intact animals but were significantly greater than in the WD group. Significantly higher lumbar enlargement syntaxin-3 in the DHA-Cur animals combined with a reduction in lipid peroxidation (4-HNE) indicated a possible healing effect on the plasma membrane. Conclusions Data in this study demonstrated that DHA-Cur can promote spinal cord neuroprotection and neutralize the clinical and biochemical effects of myelopathy. PMID:22735048
Khazaeipour, Zahra; Norouzi-Javidan, Abbas; Kaveh, Mahboobeh; Khanzadeh Mehrabani, Fatemeh; Kazazi, Elham; Emami-Razavi, Seyed-Hasan
Objective/background In patients with spinal cord injury (SCI), SCI causes psychosocial complications that vary based on culture, conditions, and the amenities of each community. Health planners and social services should have full knowledge of these issues in order to plan schedules that address them. In this study, we aimed to understand the psychosocial problems of persons with SCI in Iran and to explore the requirements for minimizing these difficulties. Design This was a descriptive cross-sectional study. Setting Brain and Spinal Cord Injury Research (BASIR) Center, Tehran University of Medical Sciences, Tehran, Iran. Participants One hundred nineteen persons with SCI referred to BASIR clinic to receive outpatient rehabilitation. Methods In this study, trained interviewers administered a questionnaire to the participants. The questionnaire consisted of socio-demographic variables and psychosocial questions about finances, employment, housing, education, and social communication problems. Results Psychosocial problems for persons with SCI are mainly associated with financial hardship due to unemployment and the high cost of living, followed by difficulties with transportation, house modification, education, marriage, social communication, sports, and entertainment. Psychological problems include sadness, depression, irritability/anger, suicidal thoughts, and a lack of self-confidence. The levels of the aforementioned problems differ with respect to sex. Conclusion Persons suffering from SCI can face some serious psychosocial problems that may vary according to sex. For example, transportation difficulties can lead to problems such as unsociability. After recognizing these problems, the next step would be providing services to facilitate a productive lifestyle, enhancing social communication and psychological health, and ultimately creating a higher quality of life. PMID:24621045
Bowers, Christian A.; Kundu, Bornali; Rosenbluth, Jeffrey; Hawryluk, Gregory W. J.
Methylprednisolone sodium succinate (MPSS) for treatment of acute spinal cord injury (SCI) has been associated with both benefits and adverse events. MPSS administration was the standard of care for acute SCI until recently when its use has become controversial. Patients with SCI have had little input in the debate, thus we sought to learn their opinions regarding administration of MPSS. A summary of the published literature to date on MPSS use for acute SCI was created and adjudicated by 28 SCI experts. This summary was then emailed to 384 chronic SCI patients along with a survey that interrogated the patients’ neurological deficits, communication with physicians and their views on MPSS administration. 77 out of 384 patients completed the survey. 28 respondents indicated being able to speak early after injury and of these 24 reported arriving at the hospital within 8 hours of injury. One recalled a physician speaking to them about MPSS and one patient reported choosing whether or not to receive MPSS. 59.4% felt that the small neurological benefits associated with MPSS were ‘very important’ to them (p<0.0001). Patients had ‘little concern’ for potential side-effects of MPSS (p = 0.001). Only 1.4% felt that MPSS should not be given to SCI patients regardless of degree of injury (p<0.0001). This is the first study to report SCI patients’ preferences regarding MPSS treatment for acute SCI. Patients favor the administration of MPSS for acute SCI, however few had input into whether or not it was administered. Conscious patients should be given greater opportunity to decide their treatment. These results also provide some guidance regarding MPSS administration in patients unable to communicate. PMID:26789007
Tian, Da-Sheng; Jing, Jue-Hua; Qian, Jun; Chen, Lei; Zhu, Bin
[Purpose] The aim of this study was to evaluate the effect of oscillating electrical field stimulation on motor function recovery and myelin regeneration in rats with spinal cord injury. [Subjects and Methods] A rat model of spinal cord injury was constructed by using the Allen weight-drop method. These rats were randomly divided into normal, spinal cord injury, and spinal cord injury + oscillating electrical field stimulation groups. The experimental group received the intervention with oscillating electrical field stimulation, and the control group received the intervention with an electrical field stimulator without oscillating electrical field stimulation. Each group was then randomly divided into seven subgroups according to observation time (1, 2, 4, 6, 8, 10, and 12 weeks). Basso-Beattie-Bresnahan score and inclined plate test score evaluation, motor evoked potential detection, and histological observation were performed. [Results] In the first 2 weeks of oscillating electrical field stimulation, the oscillating electrical field stimulation and inclined plate test scores of spinal cord injury group and spinal cord injury + oscillating electrical field stimulation group were not significantly different. In the fourth week, the scores of the spinal cord injury group were significantly lower than those of the spinal cord injury + oscillating electrical field stimulation group. The motor evoked potential incubation period in the spinal cord injury + oscillating electrical field stimulation group at the various time points was shorter than that in the spinal cord injury group. In the sixth week, the relative area of myelin in the spinal cord injury + oscillating electrical field stimulation group was evidently larger than that in the spinal cord injury group. [Conclusion] Oscillating electrical field stimulation could effectively improve spinal cord conduction function and promote motor function recovery in rats with spinal cord injury, as well as promote myelin
Patrick, Susan K.; Roy, Francois D.; Gorassini, Monica A.
The neural plasticity of spinal reflexes after two contrasting forms of walking training was determined in individuals with chronic, motor-incomplete spinal cord injury (SCI). Endurance Training involved treadmill walking for as long as possible, and Precision Training involved walking precisely over obstacles and onto targets overground. Twenty participants started either Endurance or Precision Training for 2 months and then crossed over after a 2-month rest period to the other form of training for 2 months. Measures were taken before and after each phase of training and rest. The cutaneomuscular reflex (CMR) during walking was evoked in the soleus (SOL) and tibialis anterior muscles by stimulating the posterior tibial nerve at the ankle. Clonus was estimated from the EMG power in the SOL during unperturbed walking. The inhibitory component of the SOL CMR was enhanced after Endurance but not Precision Training. Clonus did not change after either form of training. Participants with lower reflex excitability tended to be better walkers (i.e., faster walking speeds) prior to training, and the reduction in clonus was significantly correlated with the improvement in walking speed and distance. Thus, reflex excitability responded in a training-specific way, with the reduction in reflex excitability related to improvements in walking function. Trial registration number is NCT01765153. PMID:27725887
Fang, Yongkang; Huang, Xiaojiang; Wan, Yue; Tian, Hao; Tian, Yeye; Wang, Wei; Zhu, Suiqiang; Xie, Minjie
Spinal cord injury (SCI) involves complex pathological process which can be complicated by secondary injury. TREK-1 is a member of the two-pore domain potassium (K2P) channel family, which can be modulated by a number of physiological and pathological stimuli. Recent studies suggest that TREK-1 plays an active role in depression, pain and neuroprotection. However, its role in the pathological process after SCI remains unclear. In this study, we tested the expression and function of TREK-1 in spinal cord of mice after traumatic SCI. TREK-1 was widely expressed in mice spinal cord, including astrocytes and neurons. Deficiency of TREK-1 significantly exacerbated focal inflammatory responses as indicated by the increased accumulation of microglia/macrophage as well as pro-inflammatory factor interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) expression. Meanwhile, TREK-1 knockout (KO) mice showed enhanced reactive astrogliosis, chondroitin sulphate proteoglycans (CSPGs) production and decreased glutamate transporter-1(GLT-1) expression compared to the wide type mice after SCI. Furthermore, TREK-1 deficiency promoted neurons and oligodendrocytes apoptosis, aggravated demyelination, cavity formation and retarded motor recovery. In summary, our findings provide the first in vivo evidence suggesting that TREK-1 may thereby constitute a promising therapeutic target to treat acute SCI. This article is protected by copyright. All rights reserved.
Chapin, Martha H.; Holbert, Donald
This study assessed whether persons with spinal cord injuries who were successfully rehabilitated differed from those who were not with regard to positive and negative affect, life satisfaction, and depression. An ex post facto research design compared persons with spinal cord injuries who were previously employed with persons with spinal cord…
Wheaton, Benjamin J; Noor, Natassya M; Dziegielewska, Katarzyna M; Whish, Sophie; Saunders, Norman R
Developmental studies of spinal cord injury in which regrowth of axons occurs across the site of transection rarely distinguish between the recovery of motor-controlling pathways and that of ascending axons carrying sensory information. We describe the morphological changes that occur in the dorsal column (DC) of the grey short-tailed opossum, Monodelphis domestica, following spinal cord injury at two early developmental ages. The spinal cords of opossums that had had their mid-thoracic spinal cords completely transected at postnatal day 7 (P7) or P28 were analysed. Profiles of neurofilament immunoreactivity in transected cords showing DC development were differentially affected by the injury compared with the rest of the cord and cytoarchitecture was modified in an age- and site-dependent manner. The ability of DC neurites to grow across the site of transection was confirmed by injection of fluorescent tracer below the injury. P7 transected cords showed labelling in the DC above the site of original transection indicating that neurites of this sensory tract were able to span the injury. No growth of any neuronal processes was seen after P28 transection. Thus, DC is affected by spinal injury in a differential manner depending on the age at which the transection occurs. This age-differential response, together with other facets of remodelling that occur after neonatal spinal injury, might explain the locomotor adaptations and recovery observed in these animals.
1 AWARD NUMBER: W81XWH-13-1-0396 TITLE: The impact of surgical timing in acute traumatic spinal ...TYPE Annual 3. DATES COVERED 30 Sep 2013 – 29 Sep 2014 4. TITLE AND SUBTITLE The impact of surgical timing in acute traumatic spinal cord...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The optimal surgical timing following a traumatic spinal cord injury (SCI) remains controversial
Attar, A; Tuna, H; Ugur, H C; Sargon, M F; Egemen, N
It has been increasingly reported that traumatic and ischemic insults to the spinal cord may produce tissue damage through both direct and indirect mechanisms. In spite of many theories about post-traumatic spinal cord injury, there is still no satisfactory account of the exact mechanism. Vasospasm may be related to the trauma and release of vasoconstrictor or vasoactive amines. This study aims at studying the possible protective mechanisms of iloprost, a stable analogue of prostacyclin, after spinal cord injury on the rabbit. Forty-two adult male rabbits (New Zealand albino) were inflicted injuries by epidural application of an aneurysm clip to the spinal cord. Twenty-one rabbits received an i.v. infusion of 25 microg kg(-1) x h(-1) iloprost. The remaining twenty-one rabbits received an i.v. infusion of saline as the control group. Intravenous treatment started immediately after the infliction of the spinal cord injury and lasted for 1 h. Iloprost treatment had no side effects on the general physiological parameters in the rabbits. Control and iloprost treatment groups were divided into three sub-groups. The first group of animals was deeply anesthetized and spinal cords were removed 15 min after treatment. Second and third group animals were sacrificed in the 3rd and 24th hours respectively. All spinal cords were removed for light and electron microscopic examination. The width of anteriolar smooth muscle cells and the ultrastructural analysis of sulcal arterioles and venules in the ventral median fissure of spinal cords treated by iloprost revealed less thickening in all groups especially on the 24th hour group (p < 0.01), but less thickening was observed on the 3rd hour group. Iloprost-treated groups had limited edema and moderate protection of myelin and axons. These results suggest that iloprost treatment after spinal cord injury has a highly protective effect, and the possible protective effect of iloprost is resolution of vasospasm due to spinal cord injury.
Sanivarapu, Raghavendra; Vallabhaneni, Vijayalakshmi; Verma, Vivek
Current treatment for spinal cord injury (SCI) is supportive at best; despite great efforts, the lack of better treatment solutions looms large on neurological science and medicine. Curcumin, the active ingredient in turmeric, a spice known for its medicinal and anti-inflammatory properties, has been validated to harbor immense effects for a multitude of inflammatory-based diseases. However, to date there has not been a review on curcumin's effects on SCI. Herein, we systematically review all known data on this topic and juxtapose results of curcumin with standard therapies such as corticosteroids. Because all studies that compare the two show superior results for curcumin over corticosteroids, it could be true that curcumin better acts at the inflammatory source of SCI-mediated neurological injury, although this question remains unanswered in patients. Because curcumin has shown improvements from current standards of care in other diseases with few true treatment options (e.g., osteoarthritis), there is immense potential for this compound in treating SCI. We critically and systematically summarize available data, discuss clinical implications, and propose further testing of this well-tolerated compound in both the preclinical and the clinical realms. Analyzing preclinical data from a clinical perspective, we hope to create awareness of the incredible potential that curcumin shows for SCI in a patient population that direly needs improvements on current therapy. PMID:27298735
For these reasons we evaluated TRH treatment in a feline model of cervical spinal cord injury (8). Animals treated with -1...photomicrograph of lung illustrates severe pulmonary edema. Alveoli are filled with an eosinophilic , proteinaceous fluid. Scattered macrophages are...compression trauma to the feline spinal cord. J Neurosurg 55:200-208, 1981 26. Meyer GA, Berman IR, Dote DB, et al: Hemodynamic responses to acute
Santos-Nogueira, Eva; López-Serrano, Clara; Hernández, Joaquim; Lago, Natalia; Astudillo, Alma M.; Balsinde, Jesús; Estivill-Torrús, Guillermo; de Fonseca, Fernando Rodriguez; Chun, Jerold
Lysophosphatidic acid (LPA) is an extracellular lipid mediator involved in many physiological functions that signals through six known G-protein-coupled receptors (LPA1–LPA6). A wide range of LPA effects have been identified in the CNS, including neural progenitor cell physiology, astrocyte and microglia activation, neuronal cell death, axonal retraction, and development of neuropathic pain. However, little is known about the involvement of LPA in CNS pathologies. Herein, we demonstrate for the first time that LPA signaling via LPA1 contributes to secondary damage after spinal cord injury. LPA levels increase in the contused spinal cord parenchyma during the first 14 d. To model this potential contribution of LPA in the spinal cord, we injected LPA into the normal spinal cord, revealing that LPA induces microglia/macrophage activation and demyelination. Use of a selective LPA1 antagonist or mice lacking LPA1 linked receptor-mediated signaling to demyelination, which was in part mediated by microglia. Finally, we demonstrate that selective blockade of LPA1 after spinal cord injury results in reduced demyelination and improvement in locomotor recovery. Overall, these results support LPA–LPA1 signaling as a novel pathway that contributes to secondary damage after spinal cord contusion in mice and suggest that LPA1 antagonism might be useful for the treatment of acute spinal cord injury. SIGNIFICANCE STATEMENT This study reveals that LPA signaling via LPA receptor type 1 activation causes demyelination and functional deficits after spinal cord injury. PMID:26180199
Shanahan, D F; Mastroianni, G R
All accident reports involving U.S. Army OH-58 series helicopters were analyzed to determine vertical and horizontal velocity change at impact and the relationship of this kinematic data to the production of spinal injury. This analysis determined that spinal injury is related primarily to vertical velocity change at impact and is relatively independent of horizontal velocity change. The dramatic increase in the rate of spinal injury occurring just above the design sink speed of the aircraft landing gear (3.7 m/s) suggests that the fuselage and seat provide little additional impact attenuation capability above that of the gear alone. It is concluded that if this aircraft were modified to provide protection to the occupants for impacts up to 9.1 m/s (30 ft/s), approximately 80% of all spinal injury incurred in survivable accidents could be substantially mitigated. The incorporation of energy absorbing seats is recommended.
Zhang, Rui; Wang, Qihong; Li, Kai; He, Shenghong; Qin, Si; Feng, Zhenghui; Chen, Yang; Song, Pingxia; Yang, Tingyan; Zhang, Yuandong; Yu, Zhuliang; Hu, Yaohua; Shao, Ming; Li, Yuanqing
This study proposes an event-related potential (ERP) BCI-based environmental control system that integrates household electrical appliances, a nursing bed, and an intelligent wheelchair to provide daily assistance to paralyzed patients with severe spinal cord injuries (SCIs).
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
Liu, Haichun; Yang, Kaiyun; Xin, Tao; Wu, Wenliang; Chen, Yunzhen
Spinal cord injury (SCI) is one of the most serious disorders in clinics, and the high disability rate and functional deficits are common issues in patients. Transplantation of bone-marrow-derived mesenchymal stromal cells (BMSCs) into the injured spinal cord is emerging as a novel method in the therapeutics of SCI; however, its application is limited by the poor survival rate of the transplanted cells and low differentiation rate into neurons. Our laboratory recently reported that electrical stimulation (ES) dramatically improves the survival rate of transplanted BMSCs and increases spinal cord functions in animals with spinal cord injury. In this paper, we asked whether implanted electro-acupuncture (iEA) can advance the beneficial effects from the ES treatment in animals with spinal cord injury. We showed that BMSCs transplantation alone resulted in significant functional recovery in animals. Interestingly, iEA with BMSCs treatment induced a significantly higher functional improvement in locomotor functions and SSEP compared to the BMSCs treatment alone. Additionally, we used molecular biology techniques and showed that BMSCs transplantation with iEA treatment significantly increased the number of surviving BMSCs compared to the BMSCs alone group. In conclusion, our experiment showed that the approach of coupling iEA electric stimulation and BMSCs transplantation remarkably promotes functional improvements in animals with spinal cord injury and holds promising potential to treat spinal cord injury in humans.
Hubli, Michèle; Currie, Katharine D.; West, Christopher R.; Gee, Cameron M.; Krassioukov, Andrei V.
Objective/background Aortic pulse wave velocity (PWV), the gold-standard assessment of central arterial stiffness, has prognostic value for cardiovascular disease risk in able-bodied individuals. The aim of this study was to compare aortic PWV in athletes and non-athletes with spinal cord injury (SCI). Design Cross-sectional comparison. Methods Aortic PWV was assessed in 20 individuals with motor-complete, chronic SCI (C2–T5; 18 ± 8 years post-injury) using applanation tonometry at the carotid and femoral arterial sites. Ten elite hand-cyclists were matched for sex to 10 non-athletes; age and time since injury were comparable between the groups. Heart rate and discrete brachial blood pressure measurements were collected throughout testing. Outcome measures Aortic PWV, blood pressure, heart rate. Results Aortic PWV was significantly lower in athletes vs. non-athletes (6.9 ± 1.0 vs. 8.7 ± 2.5 m/second, P = 0.044). There were no significant between-group differences in resting supine mean arterial blood pressure (91 ± 19 vs. 81 ± 10 mmHg) and heart rate (60 ± 10 vs. 58 ± 6 b.p.m.). Conclusion Athletes with SCI exhibited improved central arterial stiffness compared to non-athletes, which is in agreement with the previous able-bodied literature. This finding implies that chronic exercise training may improve arterial health and potentially lower cardiovascular disease risk in the SCI population. PMID:24976366
Thomas, Christine K.; Grumbles, Robert M.
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
Dysreflexia in Spinal Cord Injury with Deep Brain Stimulation PRINCIPAL INVESTIGATOR: Jonathan R. Jagid, M.D. CONTRACTING ORGANIZATION...in Spinal Cord Injury with Deep Brain Stimulation 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0559 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT This project aims to study electrical deep brain
the respiratory pathways following spinal cord injury. J Appl Physiol. 94(2):795-810. Raineteau O and Schwab ME (2001). Plasticity of motor systems ...AD_________________ Award Number: W81XWH-13-1-0410 TITLE: " Respiratory Plasticity Following Spinal Injury: Role of Chloride-Dependent...Inhibitory Neurotransmission" PRINCIPAL INVESTIGATOR: Gordon S. Mitchell, PhD CONTRACTING ORGANIZATION: University of Wisconsin System Madison, WI 53715
Bul'on, V V; Kuznetsova, N N; Selina, E N; Kovalenko, A L; Alekseeva, L E; Sapronov, N S
Cytoflavin normalized energy metabolism, decreased the intensity of lipid peroxidation, and reactivated the antioxidant system in the spinal cord of rats with compression injury at the level of Th10-Th11. The neuroprotective effect of the test preparation manifested in normalization of hindlimb motor function and decrease in mortality rate of animals with spinal cord injury. Neuroprotective activity of cytoflavin was higher than that of Cerebrolysin.
Aim 1: Determine how loss of ASIC1a affects neurological outcome following SCI. This aim will determine how loss of the ASIC1 gene alters spinal...important role in spinal cord injury, then mice lacking the ASIC1 gene will show better behavioral recovery and less histochemical markers of lesion...ASIC1 gene and wild-type animals. Animals were sacrificed on Day 14 after injury, tissue isolated, sectioned, and histochemical analysis of
adults post-stroke, examining adaptive locomotor training in animal models and the human condition of SCI, and examining responsiveness of the...Proposal No. SC090246, Award No. W81XWH-10-1-0959 Responsiveness of a Neuromuscular Recovery Scale for Spinal Cord Injury: Inpatient and...AD_________________ Award Number: W81XWH-10-1-0959 TITLE: Responsiveness of a Neuromuscular Recovery Scale for Spinal Cord Injury: Inpatient and
AWARD NUMBER: W81XWH-12-1-0481 TITLE: The Blood-Testis Barrier and Male Sexual Dysfunction following Spinal Cord Injury PRINCIPAL INVESTIGATOR...AND SUBTITLE: l The Blood-Testis Barrier and Male Sexual Dysfunction following Spinal Cord Injury 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1...for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT A majority of males exhibit a profound loss of fertility following
Cao, Xiaoyu C; Pappalardo, Laura W; Waxman, Stephen G; Tan, Andrew M
Neuropathic pain is a major complication of spinal cord injury, and despite aggressive efforts, this type of pain is refractory to available clinical treatment. Our previous work has demonstrated a structure-function link between dendritic spine dysgenesis on nociceptive sensory neurons in the intermediate zone, laminae IV/V, and chronic pain in central nervous system and peripheral nervous system injury models of neuropathic pain. To extend these findings, we performed a follow-up structural analysis to assess whether dendritic spine remodeling occurs on superficial dorsal horn neurons located in lamina II after spinal cord injury. Lamina II neurons are responsible for relaying deep, delocalized, often thermally associated pain commonly experienced in spinal cord injury pathologies. We analyzed dendritic spine morphometry and localization in tissue obtained from adult rats exhibiting neuropathic pain one-month following spinal cord injury. Although the total density of dendritic spines on lamina II neurons did not change after spinal cord injury, we observed an inverse relationship between the densities of thin- and mushroom-shaped spines: thin-spine density decreased while mushroom-spine density increased. These structural changes were specifically noted along dendritic branches within 150 µm from the soma, suggesting a possible adverse contribution to nociceptive circuit function. Intrathecal treatment with NSC23766, a Rac1-GTPase inhibitor, significantly reduced spinal cord injury-induced changes in both thin- and mushroom-shaped dendritic spines. Overall, these observations demonstrate that dendritic spine remodeling occurs in lamina II, regulated in part by the Rac1-signaling pathway, and suggests that structural abnormalities in this spinal cord region may also contribute to abnormal nociception after spinal cord injury.
Cao, Xiaoyu C; Pappalardo, Laura W; Waxman, Stephen G
Neuropathic pain is a major complication of spinal cord injury, and despite aggressive efforts, this type of pain is refractory to available clinical treatment. Our previous work has demonstrated a structure–function link between dendritic spine dysgenesis on nociceptive sensory neurons in the intermediate zone, laminae IV/V, and chronic pain in central nervous system and peripheral nervous system injury models of neuropathic pain. To extend these findings, we performed a follow-up structural analysis to assess whether dendritic spine remodeling occurs on superficial dorsal horn neurons located in lamina II after spinal cord injury. Lamina II neurons are responsible for relaying deep, delocalized, often thermally associated pain commonly experienced in spinal cord injury pathologies. We analyzed dendritic spine morphometry and localization in tissue obtained from adult rats exhibiting neuropathic pain one-month following spinal cord injury. Although the total density of dendritic spines on lamina II neurons did not change after spinal cord injury, we observed an inverse relationship between the densities of thin- and mushroom-shaped spines: thin-spine density decreased while mushroom-spine density increased. These structural changes were specifically noted along dendritic branches within 150 µm from the soma, suggesting a possible adverse contribution to nociceptive circuit function. Intrathecal treatment with NSC23766, a Rac1-GTPase inhibitor, significantly reduced spinal cord injury-induced changes in both thin- and mushroom-shaped dendritic spines. Overall, these observations demonstrate that dendritic spine remodeling occurs in lamina II, regulated in part by the Rac1-signaling pathway, and suggests that structural abnormalities in this spinal cord region may also contribute to abnormal nociception after spinal cord injury. PMID:28326929
Reed, Jamie L.; Liao, Chia-Chi; Qi, Hui-Xin; Kaas, Jon H.
Here, we review recent work on plasticity and recovery after dorsal column spinal cord injury in nonhuman primates. Plasticity in the adult central nervous system has been established and studied for the past several decades; however, capacities and limits of plasticity are still under investigation. Studies of plasticity include assessing multiple measures before and after injury in animal models. Such studies are particularly important for improving recovery after injury in patients. In summarizing work by our research team and others, we suggest how the findings from plasticity studies in nonhuman primate models may affect therapeutic interventions for conditions involving sensory loss due to spinal cord injury. PMID:27578996
Reed, Jamie L; Liao, Chia-Chi; Qi, Hui-Xin; Kaas, Jon H
Here, we review recent work on plasticity and recovery after dorsal column spinal cord injury in nonhuman primates. Plasticity in the adult central nervous system has been established and studied for the past several decades; however, capacities and limits of plasticity are still under investigation. Studies of plasticity include assessing multiple measures before and after injury in animal models. Such studies are particularly important for improving recovery after injury in patients. In summarizing work by our research team and others, we suggest how the findings from plasticity studies in nonhuman primate models may affect therapeutic interventions for conditions involving sensory loss due to spinal cord injury.
Moon, Lawrence D. F.
Extensive research is ongoing that concentrates on finding therapies to enhance CNS regeneration after spinal cord injury (SCI) and to cure paralysis. This review sheds light on the role of the FGFR pathway in the injured spinal cord and discusses various therapies that use FGFR activating ligands to promote regeneration after SCI. We discuss studies that use peripheral nerve grafts or Schwann cell grafts in combination with FGF1 or FGF2 supplementation. Most of these studies show evidence that these therapies successfully enhance axon regeneration into the graft. Further they provide evidence for partial recovery of sensory function shown by electrophysiology and motor activity evidenced by behavioural data. We also present one study that indicates that combination with additional, synergistic factors might further drive the system towards functional regeneration. In essence, this review summarises the potential of nerve and cell grafts combined with FGF1/2 supplementation to improve outcome even after severe spinal cord injury. PMID:28197342
Moraud, Eduardo Martin; Capogrosso, Marco; Formento, Emanuele; Wenger, Nikolaus; DiGiovanna, Jack; Courtine, Grégoire; Micera, Silvestro
Epidural electrical stimulation of lumbar segments facilitates standing and walking in animal models and humans with spinal cord injury. However, the mechanisms through which this neuromodulation therapy engages spinal circuits remain enigmatic. Using computer simulations and behavioral experiments, we provide evidence that epidural electrical stimulation interacts with muscle spindle feedback circuits to modulate muscle activity during locomotion. Hypothesis-driven strategies emerging from simulations steered the design of stimulation protocols that adjust bilateral hindlimb kinematics throughout gait execution. These stimulation strategies corrected subject-specific gait and balance deficits in rats with incomplete and complete spinal cord injury. The conservation of muscle spindle feedback circuits across mammals suggests that the same mechanisms may facilitate motor control in humans. These results provide a conceptual framework to improve stimulation protocols for clinical applications.
do Vale Ramos, Renato Carlos; Alegrete, Nuno
The aim here was to conduct a review of the literature on pharmacological therapies for modifying the neurological status of patients with spinal cord injuries. The PubMed database was searched for articles with the terms "spinal cord injury AND methylprednisolone/GM1/apoptosis inhibitor/calpain inhibitor/naloxone/tempol/tirilazad", in Portuguese or in English, published over the last five years. Older studies were included because of their historical importance. The pharmacological groups were divided according to their capacity to interfere with the physiopathological mechanisms of secondary injuries. Use of methylprednisolone needs to be carefully weighed up: other anti-inflammatory agents have shown benefits in humans or in animals. GM1 does not seem to have greater efficacy than methylprednisolone, but longer-term studies are needed. Many inhibitors of apoptosis have shown benefits in in vitro studies or in animals. Naloxone has not shown benefits. Tempol inhibits the main consequences of oxidation at the level of the spinal cord and other antioxidant drugs seem to have an effect superior to that of methylprednisolone. There is an urgent need to find new treatments that improve the neurological status of patients with spinal cord injuries. The benefits from treatment with methylprednisolone have been questioned, with concerns regarding its safety. Other drugs have been studied, and some of these may provide promising alternatives. Additional studies are needed in order to reach conclusions regarding the benefits of these agents in clinical practice.
Zhou, Yulong; Ye, Libing; Zheng, Binbin; Zhu, Sipin; Shi, Hongxue; Zhang, Hongyu; Wang, Zhouguang; Wei, Xiaojie; Chen, Daqing; Li, Xiaokun; Xu, Huazi; Xiao, Jian
This study aims to investigate the role of endocytoplasmic reticulum (ER) stress induced by spinal cord injury (SCI) in blood-spinal cord barrier (BSCB) disruption and the effect of phenylbutyrate (PBA) on BSCB disruption after SCI. After a moderate contusion injury at the T9 level of spinal cord with a vascular clip, PBA was immediately administered into injured rat via intraperitoneal injection (100 mg/kg) and then further treated once a day for 2 weeks for behavior test. Spinal cord was collected at 1 day post-injury for evaluation of the effects of ER stress and PBA on BSCB disruption after SCI. PBA significantly attenuated BSCB permeability and degradation of tight junction molecules such as P120, β-catenin, Occludin and Claudin5 at 1 day after injury and improved functional recovery in the rat model of trauma. The BSCB protective effect of PBA is related to the inhibition of ER stress induced by SCI. In addition, PBA significantly inhibited the increase of ER stress markers and prevents loss of tight junction and adherens junction proteins in TG-treated human brain microvascular endothelial cells (HBMEC). Taken together, our data demonstrate that therapeutic strategies targeting ER stress may be suitable for the therapy of preserving BSCB integrity after SCI. PBA may be a new candidate as a therapeutic agent for protecting SCI by a compromised BSCB. PMID:27186310
Varela-Lage, Cristina; Alcobendas-Maestro, Mónica; Luque-Ríos, Inmaculada; Esclarín-De Ruz, Ana; Talavera-Díaz, Francisco; Ceruelo-Abajo, Silvia
Introduccion. La poblacion de mayores de 65 años activos fisicamente continua en aumento, lo que condiciona un mayor riesgo de caidas y de lesion medular en un rango de edad con importante presencia de patologia cronica. Objetivo. Revisar la incidencia, el tipo de lesion, las complicaciones asociadas y los resultados funcionales de las lesiones medulares ocurridas en pacientes mayores de 65 años. Pacientes y metodos. Estudio descriptivo retrospectivo en lesionados medulares agudos mayores de 65 años ingresados en el Hospital Nacional de Paraplejicos desde enero de 2010 hasta diciembre de 2011. Las variables del estudio fueron datos demograficos y de lesion, antecedentes personales, complicaciones ocurridas durante el ingreso y capacidad funcional al alta medida con las escalas Spinal Cord Independence Measure (SCIM III) y Walking Index Spinal Cord Injury (WISCI). Resultados. Se incluyeron 111 individuos con una media de edad de 72,5 años. La incidencia anual fue de 17,3 pacientes/100 ingresos. El 33,3% eran lesiones cervicales y fueron incompletas el 66,7%. La etiologia medica fue mas frecuente que la traumatica. El 5% no presentaba otras enfermedades intercurrentes. El 97% sufrio algun tipo de complicacion. La media alcanzada para la SCIM III fue de 42 puntos y el 35% consiguio capacidad de marcha. Conclusiones. En los ultimos años se ha producido un aumento de lesion medular en mayores de 65 años, en los que la etiologia traumatica no es superior a la medica; mas frecuentemente son lesiones incompletas que asocian mayor comorbilidad que la poblacion general, y se consiguen resultados funcionales mas pobres a pesar de las mejoras neurologicas.
Mawson, A R; Biundo, J J; Clemmer, D I; Jacobs, K W; Ktsanes, V K; Rice, J C
A retrospective case-control study was performed in New Orleans, Louisiana, in 1985-1986 to test the hypotheses that 1) criminality is a risk factor for severe injury, and 2) the association between criminality and injury can be explained in terms of a common underlying factor--increased sensation-seeking tendencies. A total of 140 males with spinal cord injury were individually matched with 140 driver's license holders on age, race, sex, educational attainment, and zip code of residence and were interviewed by telephone. Criminality prior to spinal cord injury was measured by self-report and police records, and sensation seeking was measured by the Disinhibition and Boredom Susceptibility subscales of Zuckerman's Sensation-Seeking Scale (Form V). Those with spinal cord injuries were significantly more likely than controls to report a history of juvenile delinquency, adult criminality, and incarceration prior to the time of spinal cord injury. Statistically significant but modest difference were also found between cases and controls with respect to Disinhibition, Boredom Susceptibility, and the combined Sensation-Seeking Scale score. Matched-pairs logistic regression analysis indicated that the association between sensation seeking and spinal cord injury remained significant after controlling for criminality, with an estimated relative risk of 2.05 (95% confidence interval 1.67-2.53). However, the association between criminality and spinal cord injury also remained significant after controlling for sensation seeking (estimated relative risk = 2.04, 95% confidence interval 1.09-3.82). On the basis of these results, criminality and sensation seeking may be statistically significant but independent predictors of spinal cord injury.
Poor, Charles R.
Reviews historical development of organized vocational rehabilitation programming for the spinal cord injured in the United States. Significant factors that affect vocational rehabilitation outcomes with spinal cord injured persons are listed and discussed. (Author)
Scher, A T
A 10-year review (1987-1996) of injuries sustained to the spine and spinal cord in rugby players with resultant paralysis has been undertaken. This article reviews that the incidence of serious rugby spine and spinal cord injuries in South Africa has increased over the 10-year period reviewed, despite stringent new rules instituted in an attempt to decrease the incidence of these injuries. The mechanisms of injury, as previously reported, remain the same as well as the phases of game responsible for injury of the tight scrum, tackle, rucks, and mauls. Two new observations are reported: the first is related to the occurrence of spinal cord concussion with transient paralysis, and the second is related to the increased incidence of osteoarthritis of the cervical spine in rugby players.
Sanchez, Gonzalo M.; Burridge, Alwyn L.
Dating from the seventeenth century b.c. the Edwin Smith papyrus is a unique treatise containing the oldest known descriptions of signs and symptoms of injuries of the spinal column and spinal cord. Based on a recent “medically based translation” of the Smith papyrus, its enclosed treasures in diagnostic, prognostic and therapeutic reasoning are revisited. Although patient demographics, diagnostic techniques and therapeutic options considerably changed over time, the documented rationale on spinal injuries can still be regarded as the state-of-the-art reasoning for modern clinical practice. PMID:20697750
Seçer, Mehmet; Ulutaş, Murat; Yayla, Erdal; Çınar, Kadir
INTRODUCTION This report describes a rare case of the gunshot injury of the spine and spinal cord. PRESENTATION OF CASE A rare case of the bullet lodged intra-durally in the upper cervical region without damaging the vertebrae or the spinal cord. The bullet was removed as microneurosurgical and duraplasty was performed. DISCUSSION Surgical management of the gunshot wounds of the spine and spinal cord is not widely advocated and controversial. CONCLUSION Advances in microneurosurgical instrumentation and microscopic techniques may open up a new era of surgical treatment of spinal cord gunshot wounds. PMID:24566426
Chen, Xiang Yang; Chen, Yi; Wang, Yu; Thompson, Aiko; Carp, Jonathan S.; Segal, Richard L.; Wolpaw, Jonathan R.
Spinal reflex conditioning changes reflex size, induces spinal cord plasticity, and modifies locomotion. Appropriate reflex conditioning can improve walking in rats after spinal cord injury (SCI). Reflex conditioning offers a new therapeutic strategy for restoring function in people with SCI. This approach can address the specific deficits of individuals with SCI by targeting specific reflex pathways for increased or decreased responsiveness. In addition, once clinically significant regeneration can be achieved, reflex conditioning could provide a means of re-educating the newly (and probably imperfectly) reconnected spinal cord. PMID:20590534
Patil, Rahul; Jaiswal, Gaurav; Gupta, Tarun Kumar
Penetrating spine injury (PSI) forms the third most common cause of spine injury, only next to road traffic accidents and fall. Gunshot wound (GSW) forms the major bulk of PSI. Due to easy availability of firearms and antisocial behavior, GSW which were predominant in military population is now increasingly seen in civilized society. Here, we present a detail case review of unique case of civilian GSW indirectly causing complete spinal cord injury due to shock wave generated by the bullet, along with its systematic management. PMID:26692690
Xu, Qian; Cheong, Yong-Kwan; He, Shao-Qiu; Tiwari, Vinod; Liu, Jian; Wang, Yun; Raja, Srinivasa N; Li, Jinheng; Guan, Yun; Li, Weiyan
Activation of spinal astrocytes may contribute to neuropathic pain. Adjacent astrocytes can make direct communication through gap junctions formed by connexin 43 (Cx43) in the central nervous system. Yet, the role of spinal astroglial gap junctions in neuropathic pain is not fully understood. Since Cx43 is the connexin isoform expressed preferentially in astrocytes in the spinal cord, we used a small interfering RNA (siRNA) approach to examine whether suppression of spinal Cx43 expression inhibits mechanical hypersensitivity in rats after an L5 spinal nerve ligation (SNL). SNL rats were administered intrathecal Cx43 siRNA (3μg/15μl, twice/day) or an equal amount of mismatch siRNA (control) on days 14-17 post-SNL. Cx43 siRNA, but not mismatch siRNA, alleviated mechanical hypersensitivity in SNL rats. Furthermore, Western blot analysis showed that the pain inhibition induced by Cx43 siRNA correlated with downregulation of Cx43 expression, but not that of Cx36 (the neuronal gap junction protein) or glial fibrillary acidic protein (GFAP, a marker for reactive astrocytes) in the spinal cord of SNL rats. Western blot analysis and immunohistochemistry also showed that SNL increased GFAP expression, but decreased Cx43 expression, in spinal cord. Our results provide direct evidence that selective suppression of spinal Cx43 after nerve injury alleviates neuropathic mechanical hypersensitivity. These findings suggest that in the spinal cord, the enhanced function of astroglial gap junctions, especially those formed by Cx43, may be important to neuropathic pain in SNL rats.
Fernández-López, Blanca; Romaus-Sanjurjo, Daniel; Cornide-Petronio, María Eugenia; Gómez-Fernández, Sonia; Barreiro-Iglesias, Antón; Rodicio, María Celina
Following a spinal injury, lampreys at first are paralyzed below the level of transection. However, they recover locomotion after several weeks, and this is accompanied by the regeneration of descending axons from the brain and the production of new neurons in the spinal cord. Here, we aimed to analyse the changes in the dopaminergic system of the sea lamprey after a complete spinal transection by studying the changes in dopaminergic cell numbers and dopaminergic innervation in the spinal cord. Changes in the expression of the D2 receptor were also studied. We report the full anatomical regeneration of the dopaminergic system after an initial decrease in the number of dopaminergic cells and fibres. Numbers of dopaminergic cells were recovered rostrally and caudally to the site of injury. Quantification of dopaminergic profiles revealed the full recovery of the dopaminergic innervation of the spinal cord rostral and caudal to the site of injury. Interestingly, no changes in the expression of the D2 receptor were observed at time points in which a reduced dopaminergic innervation of the spinal cord was observed. Our observations reveal that in lampreys a spinal cord injury is followed by the full anatomical recovery of the dopaminergic system. PMID:25861481
Quinzaños-Fresnedo, Jimena; Sahagún-Olmos, Roberto Carlos
In the pathophysiology of spinal cord injury, the secondary biological processes involving changes in gene expression become more important day a day. Within these changes, the expression of different microRNAs has been involved in some of the pathophysiological processes of spinal cord injury. There are several studies that describe the transient expression of microRNA in spinal cord injury, some of them related to inflammation and apoptosis and others to functional recovery and regeneration. MicroRNA may be a potential target for the treatment of spinal cord injury, modifying the processes of inflammation, oxidation, apoptosis, functional recovery and regeneration. It is necessary to continue the study of microRNAs in spinal cord injury, as well as the identification of their target genes and signaling mechanisms involved in its neurological effects. With this, the ultimate goal is the development of effective and safe therapeutic and diagnostic strategies for patients with spinal cord injury.
Panayiotou, Elena; Malas, Stavros
Spinal cord injury (SCI) is a major health burden and currently there is no effective medical intervention. Research performed over the last decade revealed that cells surrounding the central canal of the adult spinal cord and forming the ependymal layer acquire stem cell properties either in vitro or in response to injury. Following SCI activated ependymal cells generate progeny cells which migrate to the injury site but fail to produce the appropriate type of cells in sufficient number to limit the damage, rendering this physiological response mainly ineffective. Research is now focusing on the manipulation of ependymal cells to produce cells of the oligodendrocyte lineage which are primarily lost in such a situation leading to secondary neuronal degeneration. Thus, there is a need for a more focused approach to understand the molecular properties of adult ependymal cells in greater detail and develop effective strategies for guiding their response during SCI.
Thomas, Aline M.; Palma, Jaime L.; Shea, Lonnie D.
The environment within the spinal cord after injury, which changes in the progression from the acute to chronic stages, limits the extent of regeneration. The delivery of inductive factors to promote regeneration following spinal cord injury has been promising, yet, few strategies are have are versatile to allow delivery during acute or chronic injury that would facilitate screening of candidate therapies. This report investigates the intrathecal delivery of lentiviruses for long-term expression of regenerative factors. Lentivirus-filled sponges were inserted into the intrathecal space surrounding the spinal cord, with transgene expression observed within multiple cell types that persists for 12 weeks for both intact and injured spinal cord, without any apparent damage to the spinal cord tissue. Sponges loaded with lentivirus encoding for Sonic hedgehog (Shh) were investigated for acute (delivered at 0 weeks) and chronic (at 4 weeks) injuries, and for multiple locations relative to the injury. In an acute model, sponges placed directly above the injury increased oligodendrocyte and decreased astrocyte presence. Sponges placed caudal to the injury had reduced impact on oligodendrocytes and astrocytes in the injury. In a chronic model, sponges increased oligodendrocyte and decreased astrocyte presence. Furthermore, the effect of Shh was shown to be mediated in part by reduction of Bmp signaling, monitored with an Msx2-sensitive reporter vector. The implantation of lentivirus-loaded biomaterials intrathecally provides the opportunity to induce the expression of a factor at a specified time without entering the spinal cord, and has the potential to promote gene delivery within the spinal cord, which can influence the extent of regeneration. PMID:25724274
Widerström-Noga, Eva; Felix, Elizabeth R; Adcock, James P; Escalona, Maydelis; Tibbett, Jacqueline
Identifying clinical neuropathic pain phenotypes is a first step to better understand the underlying pain mechanisms after spinal cord injury (SCI). The primary purpose of the present study was to characterize multidimensional neuropathic pain phenotypes based on quantitative sensory testing (QST), pain intensity, and utilization of catastrophizing coping strategies. Thermal perception, thermal pain, and vibratory perception thresholds were assessed above and below the level of injury (LOI) in 101 persons with SCI and neuropathic pain, 18 persons with SCI and no neuropathic pain, and 50 able-bodied, pain-free controls. Cluster analysis of QST z-scores below the LOI, pain intensity ratings, and the Coping Strategies Questionnaire (CSQ) catastrophizing subscale scores in subjects with neuropathic pain resulted in two phenotypes: severe neuropathic pain (SNP) with greater pain intensity (7.39 ± 1.57) and thermal and vibratory sensitivity compared with the moderate neuropathic pain (MNP; 5.40 ± 1.43). A factor analysis including all CSQ subscales, the Neuropathic Pain Symptom Inventory (NPSI) total score, and thermal pain sensitivity above and below the LOI resulted in three factors: (1) adaptive pain coping including increasing activities, diverting attention, and reinterpreting pain sensations; (2) catastrophizing, neuropathic pain, and thermal sensitivity including greater NPSI total score, thermal pain sensitivity below the LOI, and catastrophizing; and (3) general pain sensitivity including greater thermal pain sensitivity above the LOI and lower catastrophizing. Our results suggest that neuropathic pain symptom severity post-SCI is significantly associated with residual spinothalamic tract function below the LOI and catastrophizing pain coping.
Andrada, L; De Vito, E L
The restrictive defect was quantified (Forced vital capacity, FVC) and their postural dependence and the respiratory muscle weakness (Maximal inspiratory and expiratory pressures, MIP and MEP) in 29 patients (12 to 46 years) with spinal injury from cervical (C) 4 to thoracic (T) 7 (30 days to 48 months post injury period). The FVC in C (seated) was 2200 +/- 560 ml (47.2%), and in T was 2940 +/- 750 ml (66.6%), p < 0.008. The postural dependence of the FVC was higher in C with an increase of 25% and only of 10% in the T (p < 0.03). This postural dependence was a function of the FVC according to the regression equation: FVC % (supine) = 24.73+ 0.7341* FVC % seated (r 0.8771, p < 0.001). The MIP in C was 61.59 (53.82%) +/- 17.26 cm H2O and in T was 87.25 (77.85%) +/- 24.27 cmH2O (p < 0.05). The MEP in C was 48.53 (24.97%) +/- 18.09 cm H2O, and in T was 58.75 (30.74%) +/- 27.67 cmH2O (p NS). No correlation was found between FVC and maximal statics respiratory pressures. In conclusion, the C showed more significant restrictive defect and a great postural dependence of the FVC. In both, the expiratory muscle weakness was more severe than the inspiratory group. Inspiratory muscle weakness was higher in C.
Lee, Jin-Moo; Yan, Ping; Xiao, Qingli; Chen, Shawei; Lee, Kuang-Yung; Hsu, Chung Y.; Xu, Jan
Methylprednisolone (MP) is used to treat a variety of neurological disorders involving white matter injury, including multiple sclerosis, acute disseminated encephalomyelitis, and spinal cord injury (SCI). While its mechanism of action has been attributed to anti-inflammatory or anti-oxidant properties, we examined the possibility that MP may have direct neuroprotective activities. Neurons and oligodendrocytes treated with AMPA (alpha-amino-3-hydroxy-5- methylisoxazole-4-propionate) or staurosporine died within 24 hrs after treatment. MP attenuated oligodendrocyte death in a dose-dependent manner; however, neurons were not rescued by the same doses of MP. This protective effect was reversed by the glucocorticoid receptor (GR) antagonist, RU486, and siRNA directed against GR, suggesting a receptor-dependent mechanism. MP reversed AMPA-induced decreases in the expression of antiapoptotic Bcl-xL, caspase-3 activation, and DNA laddering, suggesting anti-apoptotic activity in oligodendrocytes. To examine if MP demonstrated this selective protection in vivo, neuronal and oligodendrocyte survival was assessed in rats subjected to SCI; groups of rats were treated with or without MP in the presence or absence of RU486. Eight days after SCI, MP significantly increased oligodendrocytes (CC-1 immunoreactive cells) following SCI, but neuronal (NeuN immunoreactive cells) number remained unchanged; RU486 reversed this protective effect. MP also inhibited SCI-induced decreases in Bcl-xL and caspase-3 activation. Consistent with these findings, the volume of demyelination, assessed by Luxol Fast Blue staining, was attenuated by MP and reversed by RU486. These results suggest that MP selectively inhibits oligodendrocyte but not neuronal cell death via a receptor-mediated action, and may be a mechanism for its limited protective effect following SCI. PMID:18354017
Mallory, Grant W.; Grahn, Peter J.; Hachmann, Jan T.; Lujan, J. Luis; Lee, Kendall H.
Spinal cord injury (SCI) can be defined as a loss of communication between the brain and the body due to disrupted pathways within the spinal cord. While many promising molecular strategies have emerged to reduce secondary injury and promote axonal regrowth, there is still no effective cure and recovery of function remains limited. Functional electrical stimulation (FES) represents a strategy developed to restore motor function without the need for regenerating severed spinal pathways. Despite its technological success, however, FES has not been widely integrated into the lives of spinal cord injury survivors. In this review, we briefly discuss the limitations of existing FES technologies. Additionally, we discuss how optogenetics, a rapidly evolving technique used primarily to investigate select neuronal populations within the brain, may eventually be used to replace FES as a form of therapy for functional restoration following SCI. PMID:25659246
Yang, Yong-dong; Yu, Xing; Wang, Xiu-mei; Mu, Xiao-hong; He, Feng
Tanshinone IIA, extracted from Salvia miltiorrhiza Bunge, exerts neuroprotective effects through its anti-inflammatory, anti-oxidative and anti-apoptotic properties. This study intravenously injected tanshinone IIA 20 mg/kg into rat models of spinal cord injury for 7 consecutive days. Results showed that tanshinone IIA could reduce the inflammation, edema as well as compensatory thickening of the bladder tissue, improve urodynamic parameters, attenuate secondary injury, and promote spinal cord regeneration. The number of hypertrophic and apoptotic dorsal root ganglion (L6–S1) cells was less after treatment with tanshinone IIA. The effects of tanshinone IIA were similar to intravenous injection of 30 mg/kg methylprednisolone. These findings suggested that tanshinone IIA improved functional recovery after spinal cord injury-induced lower urinary tract dysfunction by remodeling the spinal pathway involved in lower urinary tract control.
Hong, Zhenghua; Hong, Huaxing; Chen, Haixiao; Wang, Zhangfu; Hong, Dun
Erythropoietin (EPO) is a promising therapeutic agent used in a variety of spinal cord injuries. Therefore, identifying the specific molecular pathway mediating the neuronal protective effect of EPO after spinal cord injury (SCI) is of great value to the patients concerned. Platelet-derived growth factor (PDGF)-B is an important factor in the recovery of neurological function. We explored changes in the expression of PDGF-B in spinal cord injury rats after receiving EPO treatment. We used a weight-drop contusion SCI model, and EPO treatment group rats received single doses of EPO (1,000 U/kg i.p.) immediately after the operation. Seven days after the operation, the results revealed a more rapid recovery as noted by the higher BBB scores, less disruption and more neuronal regeneration of the spinal cord in the EPO treatment group than that in the SCI group. PDGF-B expression also increased in the EPO treatment group compared to that in the SCI group (P<0.01). This study showed that PDGF-B plays a role in the neuronal protective effect of EPO on spinal cord injury in rats, which may help to explain the quick recovery after EPO treatment of spinal cord injury.
Rodicio, María Celina; Barreiro-Iglesias, Antón
Spinal cord injuries are an important sanitary and economical problem for the society. In mammals, including humans, a traumatic injury to the spinal cord leads to a loss of motor and sensorial function, which is irreversible due to the low regenerative ability of the central nervous system. In contrast to mammals, functional recovery occurs spontaneously after a complete spinal cord transection in lampreys. Functional recovery occurs because in these animals about 50% of the reticulospinal axons regenerate after injury and also because of the occurrence of processes of reorganization and plasticity of the spinal circuits. In this review, we first analyze the characteristics and regeneration ability of lampreys as compared to mammals. Then, we compile the knowledge about the process of recovery after a spinal cord injury acquired in studies using the lampreys as animal model and finally we provide some general perspectives about the molecular processes implicated in regeneration that can be investigated in a very advantageous way in this animal model and which knowledge could allow to develop new therapies for patients suffering spinal cord injury.
Mustafah, Nadia Mohd; Bakar, Noriani Abu; Yang, Chung Tze
We describe a case of 55-years-old man with a known T11 AIS C since 1985. The muscle strength of his left leg is better than the right leg and he is an active community ambulator. He walks using his right knee ankle foot orthosis without a knee lock. However, on April 2012 he had undergone a left transtibial amputation secondary to infected diabetic foot ulcer. He only had his first contact with rehabilitation team 2 months after the amputation and started on gait retraining since. Given the fact that he is a K3 level as he used to climb Batu Caves which is known to have 272 steps and he plans to continue this activity for his religious purposes, we prescribed him with prosthesis - patella tendon bearing socket, pin and lock suspension, silicone liner and energy storing foot. In conclusion, a community ambulator in dual disabilities, that is, spinal cord injury and amputee is hardly encountered due to multiple confounding factors. However, the right prosthetic prescription in patient with good prognosticating factors to ambulate will determine successful rehabilitation.
Gündüz, Ayşegül; Uzun, Nurten; Örnek, Nurettin İrem; Ünalan, Halil; Karamehmetoğlu, Şafak Sahir; Kızıltan, Meral E
Abnormal enhancement of polysynaptic brainstem reflexes has been previously reported in patients with spinal cord injury (SCI). We aimed to investigate trigemino-cervical reflex (TCR) in SCI since it may reflect alterations in the connections of trigeminal proprioceptive system and cervical motoneurons. Consecutive 14 patients with SCI and 16 healthy subjects were included in this study. All patients were in the chronic phase. TCR was recorded over sternocleidomastoid (SCM) and splenius capitis (SC) muscles by stimulation of infraorbital nerve. We measured onset latency, amplitudes and durations of responses and compared between groups. We obtained stable responses over both muscles after one sided stimulation in healthy volunteers whereas probability of TCR was decreased in patients over both SCM (78.6% vs. 100%, p=0.050) and SC (71.4% vs. 100%, p=0.022). The absence of TCR was related to use of oral baclofen (≥50mg/day). However, when present, responses of SCI group had higher amplitudes and were more persistent. We demonstrated that TCR probability was similar to healthy subjects in SCI patients who used no or low dose oral baclofen. But it had higher amplitudes and longer durations. It was not obtained in only two patients who used oral baclofen more than 50mg/day.
Xu, Jiashou; Dharmarajan, Sekhar; Johnson, Frank E
Barring unusual circumstances, sigmoid colostomy is the optimal technique for management of defecation in spinal cord injury (SCI) patients. We sought to provide evidence that a sigmoid colostomy is not difficult to perform in SCI patients and has better long-term results. The St. Louis Department of Veterans Affairs has a Commission on Accreditation of Rehabilitation Facilities (CARF)-approved SCI Unit. We reviewed the operative notes on all SCI patients who received a colostomy for fecal management by three ASCRS-certified colorectal surgeons at the St. Louis Department of Veterans Affairs from January 1, 2007 to November 26, 2012. There were 27 operations for which the recorded indication for surgery suggested that the primary disorder was SCI. Fourteen had traumatic SCI of the thoracic and/or lumbar spine and were evaluable. Of these 14 patients, 12 had laparoscopic sigmoid colostomy and two had open sigmoid colostomy. We encountered one evaluable patient with a remarkably large amount of retroperitoneal bony debris who successfully underwent laparoscopic sigmoid colostomy. In conclusion, sigmoid colostomy is the consensus optimal procedure for fecal management in SCI patients. Laparoscopic procedures are preferred. Care providers should specify sigmoid colostomy when contacting a surgeon.
Reier, Paul J; Lane, Michael A; Hall, Edward D; Teng, Y D; Howland, Dena R
Advances in the neurobiology of spinal cord injury (SCI) have prompted increasing attention to opportunities for moving experimental strategies towards clinical applications. Preclinical studies are the centerpiece of the translational process. A major challenge is to establish strategies for achieving optimal translational progression while minimizing potential repetition of previous disappointments associated with clinical trials. This chapter reviews and expands upon views pertaining to preclinical design reported in recently published opinion surveys. Subsequent discussion addresses other preclinical considerations more specifically related to current and potentially imminent cellular and pharmacological approaches to acute/subacute and chronic SCI. Lastly, a retrospective and prospective analysis examines how guidelines currently under discussion relate to select examples of past, current, and future clinical translations. Although achieving definition of the "perfect" preclinical scenario is difficult to envision, this review identifies therapeutic robustness and independent replication of promising experimental findings as absolutely critical prerequisites for clinical translation. Unfortunately, neither has been fully embraced thus far. Accordingly, this review challenges the notion "everything works in animals and nothing in humans", since more rigor must first be incorporated into the bench-to-bedside translational process by all concerned, whether in academia, clinical medicine, or corporate circles.
Khazaei, Mohamad; Ahuja, Christopher S.; Fehlings, Michael G.
Spinal cord injury (SCI) is a common cause of mortality and neurological morbidity. Although progress had been made in the last decades in medical, surgical, and rehabilitation treatments for SCI, the outcomes of these approaches are not yet ideal. The use of cell transplantation as a therapeutic strategy for the treatment of SCI is very promising. Cell therapies for the treatment of SCI are limited by several translational road blocks, including ethical concerns in relation to cell sources. The use of iPSCs is particularly attractive, given that they provide an autologous cell source and avoid the ethical and moral considerations of other stem cell sources. In addition, different cell types, that are applicable to SCI, can be created from iPSCs. Common cell sources used for reprogramming are skin fibroblasts, keratinocytes, melanocytes, CD34+ cells, cord blood cells and adipose stem cells. Different cell types have different genetic and epigenetic considerations that affect their reprogramming efficiencies. Furthermore, in SCI the iPSCs can be differentiated to neural precursor cells, neural crest cells, neurons, oligodendrocytes, astrocytes, and even mesenchymal stromal cells. These can produce functional recovery by replacing lost cells and/or modulating the lesion microenvironment. PMID:28154814
Counsell, C M; Abram, J; Gilbert, M
Spinal cord injury (SCI) is a devastating event that results in significant adjustments during the acute and rehabilitation phase. During this period, it is imperative to maintain the patient's self-esteem, reduce stress levels, encourage the expression of feelings, and provide sensory stimulation. Animal Assisted Therapy (AAT) involves the use of animals as a complement to more traditional forms of therapy. The program is based on the knowledge that animals have a positive influence on people who are ill in the healthcare setting. The Animals Heal Hearts Program (TM) has two components, pet visitation and pet therapy. Pet visitation consists of allowing a patient to have his/her own personal dog for a visit, provided there are no medical contraindications. Pet therapy is a structured program using a dog that has completed behavioral and health screening. Dogs are used in the hospital to reduce patients' stress, increase their self-esteem, and help them express feelings. The dogs provide sensory stimulation as patients view and handle the animals and learn about animals and pets. A carefully planned and evaluated program ensures that it is safe and effective.
Mustafah, Nadia Mohd; Bakar, Noriani Abu; Yang, Chung Tze
We describe a case of 55-years-old man with a known T11 AIS C since 1985. The muscle strength of his left leg is better than the right leg and he is an active community ambulator. He walks using his right knee ankle foot orthosis without a knee lock. However, on April 2012 he had undergone a left transtibial amputation secondary to infected diabetic foot ulcer. He only had his first contact with rehabilitation team 2 months after the amputation and started on gait retraining since. Given the fact that he is a K3 level as he used to climb Batu Caves which is known to have 272 steps and he plans to continue this activity for his religious purposes, we prescribed him with prosthesis – patella tendon bearing socket, pin and lock suspension, silicone liner and energy storing foot. In conclusion, a community ambulator in dual disabilities, that is, spinal cord injury and amputee is hardly encountered due to multiple confounding factors. However, the right prosthetic prescription in patient with good prognosticating factors to ambulate will determine successful rehabilitation. PMID:28053733
Hackett, Amber R.; Lee, Jae K.
NG2 cells, also known as oligodendrocyte progenitor cells, are located throughout the central nervous system and serve as a pool of progenitors to differentiate into oligodendrocytes. In response to spinal cord injury (SCI), NG2 cells increase their proliferation and differentiation into remyelinating oligodendrocytes. While astrocytes are typically associated with being the major cell type in the glial scar, many NG2 cells also accumulate within the glial scar but their function remains poorly understood. Similar to astrocytes, these cells hypertrophy, upregulate expression of chondroitin sulfate proteoglycans, inhibit axon regeneration, contribute to the glial-fibrotic scar border, and some even differentiate into astrocytes. Whether NG2 cells also have a role in other astrocyte functions, such as preventing the spread of infiltrating leukocytes and expression of inflammatory cytokines, is not yet known. Thus, NG2 cells are not only important for remyelination after SCI but are also a major component of the glial scar with functions that overlap with astrocytes in this region. In this review, we describe the signaling pathways important for the proliferation and differentiation of NG2 cells, as well as the role of NG2 cells in scar formation and tissue repair. PMID:27895617
Foxley, Susan; Baadjies, Ruth
Evidence-based patient care for those with urinary and faecal incontinence involves routine tasks that are integral to essential patient care. However, over the past few decades, researchers have demonstrated how ritualistic practice in this area has become. There is also a growing range of skin care products that can be used to prevent incontinence-associated dermatitis and for nurses, deciding which ones to use can be problematic Incontinent patients have a 22% higher risk of developing pressure ulcers - when immobile this risk increases to 30% - and the often indiscriminate use of various lotions, without a significant evidence base, is a growing cause of concern. Maintaining healthy skin for those patients who have a spinal cord injury and also experience urinary and faecal incontinence is a challenge faced by nurses in primary and secondary care. Research undertaken in secondary care demonstrates that standardization to an evidence-based skin care regime, to be used after incontinent episodes, improves patient care in this specialist area.
Li, Jun; Lepski, Guilherme
Cell transplantation, as a therapeutic intervention for spinal cord injury (SCI), has been extensively studied by researchers in recent years. A number of different kinds of stem cells, neural progenitors, and glial cells have been tested in basic research, and most have been excluded from clinical studies because of a variety of reasons, including safety and efficacy. The signaling pathways, protein interactions, cellular behavior, and the differentiated fates of experimental cells have been studied in vitro in detail. Furthermore, the survival, proliferation, differentiation, and effects on promoting functional recovery of transplanted cells have also been examined in different animal SCI models. However, despite significant progress, a “bench to bedside” gap still exists. In this paper, we comprehensively cover publications in the field from the last years. The most commonly utilized cell lineages were covered in this paper and specific areas covered include survival of grafted cells, axonal regeneration and remyelination, sensory and motor functional recovery, and electrophysiological improvements. Finally we also review the literature on the in vivo tracking techniques for transplanted cells. PMID:23484157
Goulão, Miguel; Lepore, Angelo C.
A large body of work has been published on transplantation of a wide range of neural stem and progenitor cell types derived from the developing and adult CNS, as well as from pluripotent embryonic stem cells, in models of traumatic spinal cord injury (SCI). However, many of these cell-based approaches present practical issues for clinical translation such as ethical cell derivation, generation of potentially large numbers of homogenously prepared cells, and immune rejection. With the advent of induced Pluripotent Stem (iPS) cell technology, many of these issues may potentially be overcome. To date, a number of studies have demonstrated integration, differentiation into mature CNS lineages, migration and long-term safety of iPS cell transplants in a variety of SCI models, as well as therapeutic benefits in some cases. Given the clinical potential of this advance in stem cell biology, we present a concise review of studies published to date involving iPS cell transplantation in animal models of SCI. PMID:26201863
Tashima, Ryoichi; Mikuriya, Satsuki; Tomiyama, Daisuke; Shiratori-Hayashi, Miho; Yamashita, Tomohiro; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto
Accumulating evidence indicates that peripheral nerve injury (PNI) activates spinal microglia that are necessary for neuropathic pain. Recent studies using bone marrow (BM) chimeric mice have reported that after PNI, circulating BM-derived cells infiltrate into the spinal cord and differentiate into microglia-like cells. This raises the possibility that the population of spinal microglia after PNI may be heterogeneous. However, the infiltration of BM cells in the spinal cord remains controversial because of experimental adverse effects of strong irradiation used for generating BM chimeric mice. In this study, we evaluated the PNI-induced spinal infiltration of BM-derived cells not only by irradiation-induced myeloablation with various conditioning regimens, but also by parabiosis and mice with genetically labelled microglia, models without irradiation and BM transplantation. Results obtained from these independent approaches provide compelling evidence indicating little contribution of circulating BM-derived cells to the population of spinal microglia after PNI. PMID:27005516
Creasey, Graham H; Lateva, Zoia C; Schüssler-Fiorenza Rose, Sophia Miryam; Rose, Jon
Patients with both a spinal cord injury (SCI) and traumatic brain injury (TBI) are often very difficult to manage and can strain the resources of clinical units specialized in treating either diagnosis. However, a wide range of estimates exists on the extent of this problem. The aim of this study was to describe the scope of the problem in a well-defined population attending a comprehensive SCI unit. Electronic medical records of all patients with SCI being followed by the SCI unit in a U.S. Veterans' hospital were searched to identify those with concurrent TBI. The data were analyzed for age, sex, cause of injury, level and completeness of SCI, cognitive impairment, relationship with Active Duty military, and date of injury. Of 409 Veterans with a traumatic SCI, 99 (24.2%) were identified as having had a concurrent TBI. The occurrence did not appear to be closely related to military conflict. Reports of TBI were much more common in the last 20 yr than in previous decades. Documentation of TBI in patients with SCI was inconsistent. Improved screening and documentation could identify all patients with this dual diagnosis and facilitate appropriate management.
Crosby, Nathan D; Weisshaar, Christine L; Winkelstein, Beth A
Excessive stretch of the cervical facet capsular ligament induces persistent pain and spinal plasticity at later time points. Yet, it is not known when such spinal modifications are initiated following this painful injury. This study investigates the development of hyperalgesia and neuronal hyperexcitability in the spinal cord after a facet joint injury. Behavioral sensitivity was measured in a model of painful C6/C7 facet joint injury in the rat, and neuronal hyperexcitability in the spinal cord was evaluated at 6h and 1 day after injury or a sham procedure, in separate groups. Extracellular recordings of C6/C7 dorsal horn neuronal activity (229 neurons) were used to quantify spontaneous and evoked firing. Rats exhibited no change in sensitivity to mechanical stimulation of the forepaw at 6h, but did exhibit increased sensitivity at 1 day after injury (p=0.012). At 6h, both spontaneous neuronal activity and firing evoked by light brushing, pinch, and von Frey filaments (1.4-26g) applied at the forepaw were not different between sham and injury. At 1 day, spontaneous firing was noted in a greater number of neurons after injury than sham (p<0.04). Evoked firing was also increased 1 day after injury compared to normal and sham (p<0.03). Dorsal horn hyperexcitability and increased spontaneous firing developed between 6 and 24h after painful facet injury, suggesting that the development of hyperalgesia parallels dorsal horn hyperexcitability following mechanical facet joint injury, and these spinal mechanisms are initiated as early as 1 day after injury.
Wang, Yong Tai; Chang, Li-Shan; Chen, Shihui; Zhong, Yaping; Yang, Yi; Li, Zhanghua; Madison, Timothy
Individuals with spinal cord injuries (SCI) rarely participate in health-promotion programs or wellness screenings due to the lack of accessibility, adaptations, and tertiary healthcare providers. An unconditioned body is more prone to suffer injury and is at risk for more severe health problems than a conditioned one. As is common in individuals…
Anderson, James F.; Dyson, Laronistine; Grandison, Terry
Traumatic spinal cord injuries resulting from criminal violence is a growing public health concern. Citing the criminal justice system's failure to reduce violence and the costs of treating injuries, a public health-education approach is advocated. Approaches to prevention, gun control, and a comprehensive family policy are discussed. (Author/EMK)
Because the onset of a spinal cord injury may involve a brush with death and because serious injury and disability can act as a reminder of death, death anxiety was examined as a predictor of posttraumatic stress levels among individuals with disabilities. This cross-sectional study used multiple regression and multivariate multiple regression to…
Young, Amanda E.; Murphy, Gregory C.
A survey of 168 employed people who suffered spinal cord injuries found that 50% were employed after injury; 61% thought they could have benefitted from additional services such as discussion of options and follow-up on vocational issues. Dissatisfaction with employment status was related to perceived need for more services. (Contains 20…
Krause, James S.; Broderick, Lynne
We investigated relationships among personality, locus of control, and current post-injury employment status for 1,391 participants with spinal cord injury. Participants with higher internality locus-of-control scores and activity scores (personality) reported more favorable employment outcomes. Higher scores on chance and powerful others (locus…
Frigon, Alain; Johnson, Michael D; Heckman, C J
Spinal reflexes are modified by spinal cord injury (SCI) due the loss of excitatory inputs from supraspinal structures and changes within the spinal cord. The stretch reflex is one of the simplest pathways of the central nervous system and was used presently to evaluate how inputs from primary and secondary muscle spindles interact with spinal circuits before and after spinal transection (i.e., spinalization) in 12 adult decerebrate cats. Seven cats were spinalized and allowed to recover for 1 mo (i.e., chronic spinal state), whereas 5 cats were evaluated before (i.e., intact state) and after acute spinalization (i.e., acute spinal state). Stretch reflexes were evoked by stretching the left triceps surae (TS) muscles. The force evoked by TS muscles was recorded along with the activity of several hindlimb muscles. Stretch reflexes were abolished in the acute spinal state due to an inability to activate TS muscles, such as soleus (Sol) and lateral gastrocnemius (LG). In chronic spinal cats, reflex force had partly recovered but Sol and LG activity remained considerably depressed, despite the fact that injecting clonidine could recruit these muscles during locomotor-like activity. In contrast, other muscles not recruited in the intact state, most notably semitendinosus and sartorius, were strongly activated by stretching TS muscles in chronic spinal cats. Therefore, stretch reflex pathways from TS muscles to multiple hindlimb muscles undergo functional reorganization following spinalization, both acute and chronic. Altered activation patterns by stretch reflex pathways could explain some sensorimotor deficits observed during locomotion and postural corrections after SCI.
Wilt, Timothy J; Carlson, Kathleen F; Goldish, Gary D; MacDonald, Roderick; Niewoehner, Catherine; Rutks, Indulis; Shamliyan, Tatyana; Tacklind, James; Taylor, Brent C; Kane, Robert L
OBJECTIVES To assess the prevalence of carbohydrate and lipid disorders in adults with chronic spinal cord injury and evaluate their risk contribution to cardiovascular diseases and the potential impact of exercise and pharmacologic and dietary therapies to alter these disorders and reduce cardiovascular disease risk. DATA SOURCES MEDLINE (PubMed), Cochrane Database and Web sites of the American Spinal Injury Association, American Paraplegia Society, Paralyzed Veterans of America, Consortium of Spinal Cord Medicine, and WorldCat through August 2007. REVIEW METHODS English language observational studies addressing prevalence of carbohydrate and lipid disorders were included if they evaluated at least 100 adults with chronic spinal cord injury or a total of 100 subjects if using a control group. Epidemiologic investigations of more than 50 adults with spinal cord injury that were published in English after 1990 and reported cardiovascular morbidity and mortality were abstracted. Intervention studies from 1996-2007 were included regardless of design or size if they assessed exercise, diet, or pharmacologic therapies and reported carbohydrate, lipid, or cardiovascular outcomes. RESULTS The quality of evidence regarding the prevalence, impact, and outcomes of carbohydrate and lipid disorders in adults with chronic spinal cord injuries is weak. Evidence is limited by relatively few studies, small sample size, lack of appropriate control groups, failure to adjust for known confounding variables, and variation in reported outcomes. However, the existing evidence does not indicate that adults with spinal cord injuries are at markedly greater risk for carbohydrate and lipid disorders or subsequent cardiovascular morbidity and mortality than able-bodied adults. Body mass index is not reliable for assessing body composition, especially percent body fat, in adults with spinal cord injury. There are no high quality studies evaluating the impact of exercise, diet, or
Khanjani, Mohammad Saeed; Younesi, Seyed Jalal; Khankeh, Hamid Reza; Azkhosh, Manouchehr
Introduction There is increasing evidence regarding people’s reactions to life stressors in which people also may show positive experiences following a traumatic event. The aim of the present study was to explain the facilitators of post-traumatic growth based on the experiences of patients with a spinal cord injury. Methods This was a qualitative study conducted on 16 Iranian patients with a spinal cord injury using semistructured, in-depth interviews, and content analysis in 2015. These participants, despite their spinal cord injury, were successful in their lives and were considered successful members of society. A purposive sampling method was used until reaching data saturation, and then the collected data were analyzed using a content analysis method. Results The study revealed several factors as facilitators of post-traumatic growth in the patients. The extracted facilitators were put into seven categories of main concepts, including existence of support resources, contact with spinal cord injury associations, spiritual beliefs, positive attitude toward injury, access to proper facilities, enhancement of knowledge and awareness, and active presence in society. Conclusion Different factors may facilitate post-traumatic growth in patients with a spinal cord injury. Understanding these facilitators may help us in designing educational, support, and consulting programs for patients and their families as well as to the correct the support programs. PMID:28243405
Mar, Fernando M; da Silva, Tiago F; Morgado, Marlene M; Rodrigues, Lorena G; Rodrigues, Daniel; Pereira, Marta I L; Marques, Ana; Sousa, Vera F; Coentro, João; Sá-Miranda, Clara; Sousa, Mónica M; Brites, Pedro
Lack of axon regeneration following spinal cord injury has been mainly ascribed to the inhibitory environment of the injury site, i.e., to chondroitin sulfate proteoglycans (CSPGs) and myelin-associated inhibitors (MAIs). Here, we used shiverer (shi) mice to assess axon regeneration following spinal cord injury in the presence of MAIs and CSPG but in the absence of compact myelin. Although in vitro shi neurons displayed a similar intrinsic neurite outgrowth to wild-type neurons, in vivo, shi fibers had increased regenerative capacity, suggesting that the wild-type spinal cord contains additional inhibitors besides MAIs and CSPG. Our data show that besides myelin protein, myelin lipids are highly inhibitory for neurite outgrowth and suggest that this inhibitory effect is released in the shi spinal cord given its decreased lipid content. Specifically, we identified cholesterol and sphingomyelin as novel myelin-associated inhibitors that operate through a Rho-dependent mechanism and have inhibitory activity in multiple neuron types. We further demonstrated the inhibitory action of myelin lipids in vivo, by showing that delivery of 2-hydroxypropyl-β-cyclodextrin, a drug that reduces the levels of lipids specifically in the injury site, leads to increased axon regeneration of wild-type (WT) dorsal column axons following spinal cord injury. In summary, our work shows that myelin lipids are important modulators of axon regeneration that should be considered together with protein MAIs as critical targets in strategies aiming at improving axonal growth following injury.
Background Glutamergic excitotoxicity has been shown to play a deleterious role in the pathophysiology of spinal cord injury (SCI). The aim of this study was to investigate the neuroprotective effect of dizocilpine maleate, MK801 (2 mg/Kg, 30 min and 6 hours after injury) in a mice model of SCI. The spinal cord trauma was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy. Results Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration and apoptosis. In this study we clearly demonstrated that administration of MK801 attenuated all inflammatory parameters. In fact 24 hours after injury, the degree of spinal cord inflammation and tissue injury (evaluated as histological score), infiltration of neutrophils, NF-κB activation, iNOS, cytokines levels (TNF-α and IL-1β), neurotrophin expression were markedly reduced by MK801 treatment. Moreover, in a separate set of experiments, we have demonstrated that MK801 treatment significantly improved the recovery of locomotory function. Conclusions Blockade of NMDA by MK801 lends support to the potential importance of NMDA antagonists as therapeutic agents in the treatment of acute spinal cord injury. PMID:21492450
Dobran, Mauro; Iacoangeli, Maurizio; Di Somma, Lucia Giovanna Maria; Di Rienzo, A.; Colasanti, Roberto; Nocchi, Niccolò; Alvaro, Lorenzo; Moriconi, Elisa; Nasi, Davide; Scerrati, Massimo
Background: Traumatic thoracolumbar spinal fractures represent approximately 65% of all traumatic spinal fractures and are frequently associated to permanent disability with significant social and economic impact. These injuries create severe physical limitations depending on neurological status, level of fracture, severity of injury, patient age and comorbidities. Predicting neurological improvement in patients with traumatic spinal cord injuries (SCIs) is very difficult because it is related to different preoperative prognostic factors. We evaluated the neurological improvement related to the preoperative neurological conditions and the anatomic level of spinal cord injury. Methods: From January 2004 to June 2010, we operated 207 patients for unstable thoracolumbar spinal fractures. We carried out a retrospective analysis of 69 patients with traumatic SCIs operated on by a posterior fixation performed within 24 hours from the trauma. The preoperative neurological conditions (ASIA grade), the type of the fracture, the anatomic level of spinal cord injury and the postoperative neurological improvement were evaluated for each patient. Results: The ASIA grade at admission (P = 0,0005), the fracture type according to the AO spine classification (P = 0,0002), and the anatomic location of the injury (P = 0,0213) represented predictive factors of neurological improvement at univariate analysis. The preoperative neurological status (P = 0,0491) and the fracture type (P = 0,049) confirmed a positive predictive value also in the multivariate analysis. Conclusions: Our study confirms that the preoperative neurological status, the fracture type and the anatomic location of the fracture are predictive factors of the neurological outcome in patients with spinal cord injury. PMID:25289154
Sufianova, G Z; Usov, L A; Sufianov, A A; Perelomov, Iu P; Raevskaia, L Iu; Shapkin, A G
Possibilities of the neuroprotector therapy using adenosine and cyclopentyladenosine (CPA), an adenosine receptor agonist, were studied on a model of spinal cord injury by compression in rats (most closely reproducing the analogous clinical pathological process in humans). The model was induced by slow, graded compression of the spinal cord at the thoracic level. Adenosine and CPA were introduced 60 min before injury by subcutaneous injections in a dose of 300 and 2.5 micrograms/kg, respectively. The protective effect was judged by comparing the neurological, electromyographic, and histopathological changes in animals with the model injury and in the control group (adenosine and CPA background). The A1-agonist CPA injections produced a pronounced, statistically significant neuroprotector effect on the given spinal cord injury model in rats. The neuroprotective effect of adenosine was significant but not as strong. It is concluded that it is expedient to use A-agonists in clinics.
Siebert, Justin R.; Eade, Amber M.; Osterhout, Donna J.
While advances in technology and medicine have improved both longevity and quality of life in patients living with a spinal cord injury, restoration of full motor function is not often achieved. This is due to the failure of repair and regeneration of neuronal connections in the spinal cord after injury. In this review, the complicated nature of spinal cord injury is described, noting the numerous cellular and molecular events that occur in the central nervous system following a traumatic lesion. In short, postinjury tissue changes create a complex and dynamic environment that is highly inhibitory to the process of neural regeneration. Strategies for repair are outlined with a particular focus on the important role of biomaterials in designing a therapeutic treatment that can overcome this inhibitory environment. The importance of considering the inherent biological response of the central nervous system to both injury and subsequent therapeutic interventions is highlighted as a key consideration for all attempts at improving functional recovery. PMID:26491685
Lemmon, Vance P; Ferguson, Adam R; Popovich, Phillip G; Xu, Xiao-Ming; Snow, Diane M; Igarashi, Michihiro; Beattie, Christine E; Bixby, John L
The lack of reproducibility in many areas of experimental science has a number of causes, including a lack of transparency and precision in the description of experimental approaches. This has far-reaching consequences, including wasted resources and slowing of progress. Additionally, the large number of laboratories around the world publishing articles on a given topic make it difficult, if not impossible, for individual researchers to read all of the relevant literature. Consequently, centralized databases are needed to facilitate the generation of new hypotheses for testing. One strategy to improve transparency in experimental description, and to allow the development of frameworks for computer-readable knowledge repositories, is the adoption of uniform reporting standards, such as common data elements (data elements used in multiple clinical studies) and minimum information standards. This article describes a minimum information standard for spinal cord injury (SCI) experiments, its major elements, and the approaches used to develop it. Transparent reporting standards for experiments using animal models of human SCI aim to reduce inherent bias and increase experimental value.
Ferguson, Adam R.; Popovich, Phillip G.; Xu, Xiao-Ming; Snow, Diane M.; Igarashi, Michihiro; Beattie, Christine E.; Bixby, John L.
Abstract The lack of reproducibility in many areas of experimental science has a number of causes, including a lack of transparency and precision in the description of experimental approaches. This has far-reaching consequences, including wasted resources and slowing of progress. Additionally, the large number of laboratories around the world publishing articles on a given topic make it difficult, if not impossible, for individual researchers to read all of the relevant literature. Consequently, centralized databases are needed to facilitate the generation of new hypotheses for testing. One strategy to improve transparency in experimental description, and to allow the development of frameworks for computer-readable knowledge repositories, is the adoption of uniform reporting standards, such as common data elements (data elements used in multiple clinical studies) and minimum information standards. This article describes a minimum information standard for spinal cord injury (SCI) experiments, its major elements, and the approaches used to develop it. Transparent reporting standards for experiments using animal models of human SCI aim to reduce inherent bias and increase experimental value. PMID:24870067
Jung, Sun-Young; Seo, Tae-Beom; Kim, Dae-Young
Spinal cord injury (SCI) disrupts both axonal pathways and segmental spinal cord circuity, resulting in permanent neurological deficits. Physical exercise is known to increase the expression of neurotrophins for improving the injured spinal cord. In the present study, we investigated the effects of treadmill exercise on locomotor function in relation with brain-derived neurotrophic factor (BDNF) expression after SCI. The rats were divided into five groups: control group, sham operation group, sham operation and exercise group, SCI group, and SCI and exercise group. The laminectomy was performed at the T9–T10 level. The exposed dorsal surface of the spinal cord received contusion injury (10 g × 25 mm) using the impactor. Treadmill exercise was performed 6 days per a week for 6 weeks. In order to evaluate the locomotor function of animals, Basso-Beattie-Bresnahan (BBB) locomotor scale was conducted once a week for 6 weeks. We examined BDNF expression and axonal sprouting in the injury site of the spinal cord using Western blot analysis and immunofluorescence staining. SCI induced loss of locomotor function with decreased BDNF expression in the injury site. Treadmill exercise increased the score of BBB locomotor scale and reduced cavity formation in the injury site. BDNF expression and axonal sprouting within the trabecula were further facilitated by treadmill exercise in SCI-exposed rats. The present study provides the evidence that treadmill exercise may facilitate recovery of locomotor function through axonal regeneration via BDNF expression following SCI. PMID:27656624
Brink, Farah W; Gold, Delia L; Adler, Brent; Letson, Megan McGraw
Distraction injury of the spine with spinal cord transection and adjacent vascular injury is rarely described in the setting of child physical abuse. We report a 5-week-old infant boy who sustained these injuries after an abusive event. The clinical presentation, imaging findings, and recommended evaluation modalities are discussed. An overview of pediatric spinal column and vascular injuries secondary to physical abuse is given.
Sharma, Siddhartha; Singh, Manjeet; Wani, Iftikhar H; Sharma, Sushil; Sharma, Narendra; Singh, Dara
Background This study is aimed to determine the clinical and radiological corellations of adult patients with Spinal Cord Injury Without Radiographic Abnormalities (SCIWORA). Methods The study population consisted of all adult patients with suspected cervical spine injury. SCIWORA was defined as the presence of either no injury or a neural injury on Magnetic Resonance Imaging (MRI) in the absence of radiographic or Computed Tomographic (CT) Scan findings suggestive of trauma in patients with neurological deficit. Purely extra neural compressive lesions were excluded from the study. Results Twelve of ninety seven (12.4%) patients had a neural injury on MRI with normal radiographs and CT scan. These included cord contusion in five cases, cord edema in five cases and cord hemorrhage in two cases. Ten patients were managed conservatively and two patients with disc prolapse were managed surgically. All patients showed at least one ASIA Impairment Scale (AIS) grade improvement and three patients (25%) recovered completely. Conclusions Parenchymal spinal cord injury is the single most important determinant in the long term outcome of adult SCIWORA patients. Cord hemorrhage has the worst prognosis and cord edema has the best. Longitudinal signal extension and associated extra neural injuries are also associated with poorer outcomes. Cases with purely neural injuries can be managed conservatively, but associated extra neural injuries, especially disc prolapse and ligamentous instability, warrant surgical management. Keywords Post Traumatic Myelopathy; Spinal Cord Trauma; Computed tomography; Magnetic resonance imaging; SCIWORA PMID:22493651
Bailey, Aaron Z.; Mi, Yiqun P.; Nelson, Aimee J.
Background Short-latency afferent inhibition (SAI) results when somatosensory afferent input inhibits the corticospinal output from primary motor cortex (M1). The present study examined SAI in the flexor carpi radialis (FCR) muscle in individuals with spinal cord injury (SCI) and uninjured controls. Methods Short-latency afferent inhibition (SAI) was evoked by stimulating the median nerve at the elbow at intervals of 15, 20 and 25 ms in advance of a transcranial magnetic stimulation (TMS) pulse over M1. SAI was tested with the FCR at rest and also during ~20% of maximum voluntary contraction. Corticospinal output was assessed through measuring both motor thresholds and motor evoked potential (MEP) recruitment curves. The afferent volley was assessed via the N20–P25 amplitude of the somatosensory evoked potential (SEP) and the amplitude of sensory nerve action potentials (SNAP) recorded over the median nerve at the elbow. Results SAI is reduced in SCI in both the contracted and non-contracted FCR muscle. MEP recruitment curves and thresholds were decreased in SCI only in the active state and not the resting state. N20–P25 amplitude was similar between groups in both the resting and active states although SNAP was significantly reduced in SCI at rest. Conclusions We conclude that reduced SAI in SCI is likely attributed to neuroplasticity altering the intrinsic M1 circuitry mediating SAI and/or reduced afferent input traversing a direct thalamocortical route to M1. These data provide a new avenue of research aimed at identifying therapeutic approaches to alter SAI to improve upper limb function in individuals with SCI. PMID:28123808
Jegede, Adejoke B.; Rosado-Rivera, Dwindally; Bauman, William A.; Cardozo, Christopher P.; Sano, Mary; Moyer, Jeremy M.; Brooks, Monifa; Wecht, Jill Maria
Background Due to sympathetic de-centralization, individuals with spinal cord injury (SCI), especially those with tetraplegia, often present with hypotension, worsened with upright posture. Several investigations in the non-SCI population have noted a relationship between chronic hypotension and deficits in memory, attention and processing speed and delayed reaction times. Objective To determine cognitive function in persons with SCI who were normotensive or hypotensive over a 24-h observation period while maintaining their routine activities. Methods Subjects included 20 individuals with chronic SCI (2–39 years), 13 with tetraplegia (C4–8) and 7 with paraplegia (T2–11). Individuals with hypotension were defined as having a mean 24-h systolic blood pressure (SBP) below 110 mmHg for males and 100 mmHg for females, and having spent ≥50% of the total time below these gender-specific thresholds. The cognitive battery used included assessment of memory (CVLT), attention and processing speed (Digit Span, Stroop word and color and Oral Trails A), language (COWAT) and executive function (Oral Trails B and Stroop color–word). Results Demographic parameters did not differ among the hypotensive and normotensive groups; the proportion of individuals with tetraplegia (82%) was higher in the hypotensive group. Memory was significantly impaired (P<0.05) and there was a trend toward slowed attention and processing speed (P<0.06) in the hypotensive compared to the normotensive group. Interpretation These preliminary data suggest that chronic hypotension in persons with SCI is associated with deficits in memory and possibly attention and processing speed, as previously reported in the non-SCI population. PMID:19842013
Background The final months of the conflict in Sri Lanka in 2009 resulted in massive displacement of the civilian population and a high volume of orthopedic trauma including spinal cord injury. In response to this need, Médecins Sans Frontières implemented a multidisciplinary rehabilitation program. Methods Patients were admitted to the program if they had a spinal cord injury, a stable spine and absence of a high-grade pressure ulcer. All patients were assessed on admission with a standardized functional scale the Spinal Cord Independence Measure II (SCIM) and the American Spinal Injury Association Impairment Scale (ASIA). A multidisciplinary team provided nursing care, physiotherapy, bowel and bladder training, mental health care, and vocational rehabilitation. Patients were discharged from the program when medically stable and able to perform activities of daily living independently or with assistance of a caregiver. The primary outcome measures were discharge to the community, and change in SCIM score on discharge. Secondary outcome measures were measured at 6-12 weeks post-discharge, and included SCIM score and presence of complications (pressure ulcers, urinary tract infections and bowel problems). Results 89 patients were admitted. The majority of injuries were to the thoracic region or higher (89%). The injuries were classified as ASIA grade A in 37 (43%), grade B in 17(20%), grade C in 15 (17%) and grade D in 17(20%). 83.2% met the criteria for discharge, with a further 7.9% patients requiring transfer to hospital for surgical care of pressure ulcers. There was a significant change in SCIM score from 55 on admission to 71 on discharge (p < 0.01). 79.8% and 66.7% achieved a clinically significant and substantially significant SCIM score improvement, respectively. Amongst those with follow up data, there was a reduction in post spinal cord injury complications from those experienced either at or during admission. A further 79% of SCIM scores were
Beer-Furlan, André Luiz; Paiva, Wellingson Silva; Tavares, Wagner Malagó; de Andrade, Almir Ferreira; Teixeira, Manoel Jacobsen
Introduction: Stab wounds resulting in spinal cord injuries are very rare. In direct central back stabbings, the layers of muscles and the spinal column tends to deflect blades, rarely causing injuries to the spinal cord. We report an unusual case of traumatic spinal cord injury by a screwdriver stab, presented as Brown-Séquard syndrome and discuss possible pitfalls on the surgical treatment. Case report: A 34 year-old man was brought to the emergency department after a group assault with a single screwdriver stab wound on the back. Neurological examination revealed an incomplete Brown-Sequard syndrome, with grade IV motor deficit on the left leg and contralateral hemihypoalgesia below T9 level. Radiological evaluation showed a retained 9 cm screwdriver that entered and trespassed the spinal canal at T6 level, reaching the posterior mediastinum with close relation to the thoracic aorta. Vascular injury could not be excluded. The joint decision between the neurosurgery and the vascular surgery teams was the surgical removal of the screwdriver under direct visualization. A left mini-thoracotomy was performed. Simultaneously, a careful dissection was done and screwdriver was firmly pulled back on the opposite path of entry under direct visualization of the aorta. The neurological deficit was maintained immediately after the surgical procedure. Follow-up visit after 1 year showed minor motor deficit and good healing. Conclusions: It is important to consider all aspects of secondary injury on the surgical planning of penetrating spinal cord injury. The secondary injury can be minimized with multidisciplinary planning of the surgical procedure. PMID:24482724
Bráz, JM; Sharif-Naeini, R; Vogt, D; Kriegstein, A; Alvarez-Buylla, A; Rubenstein, JL; Basbaum, AI
Neuropathic pain is a chronic debilitating disease characterized by mechanical allodynia and spontaneous pain. Because symptoms are often unresponsive to conventional methods of pain treatment, new therapeutic approaches are essential. Here, we describe a strategy that not only ameliorates symptoms of neuropathic pain, but is also potentially disease modifying. We show that transplantation of immature telencephalic GABAergic interneurons from the mouse medial ganglionic eminence (MGE) into the adult mouse spinal cord completely reverses the mechanical hypersensitivity produced by peripheral nerve injury. Underlying this improvement is a remarkable integration of the MGE transplants into the host spinal cord circuitry, in which the transplanted cells make functional connections with both primary afferent and spinal cord neurons. By contrast, MGE transplants were not effective against inflammatory pain. Our findings suggest that MGE-derived GABAergic interneurons overcome the spinal cord hyperexcitability that is a hallmark of nerve-injury induced neuropathic pain. PMID:22632725
Wenger, Nikolaus; Moraud, Eduardo Martin; Gandar, Jerome; Musienko, Pavel; Capogrosso, Marco; Baud, Laetitia; Le Goff, Camille G.; Barraud, Quentin; Pavlova, Natalia; Dominici, Nadia; Minev, Ivan R.; Asboth, Leonie; Hirsch, Arthur; Duis, Simone; Kreider, Julie; Mortera, Andrea; Haverbeck, Oliver; Kraus, Silvio; Schmitz, Felix; DiGiovanna, Jack; van den Brand, Rubia; Bloch, Jocelyne; Detemple, Peter; Lacour, Stéphanie P.; Bézard, Erwan; Micera, Silvestro; Courtine, Grégoire
Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited this therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here, we developed novel stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real–time control software that modulate extensor versus flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight–bearing capacities, endurance and skilled locomotion in multiple rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans. PMID:26779815
Ren, Yilong; Ao, Yan; O’Shea, Timothy M.; Burda, Joshua E.; Bernstein, Alexander M.; Brumm, Andrew J.; Muthusamy, Nagendran; Ghashghaei, H. Troy; Carmichael, S. Thomas; Cheng, Liming; Sofroniew, Michael V.
Ependyma have been proposed as adult neural stem cells that provide the majority of newly proliferated scar-forming astrocytes that protect tissue and function after spinal cord injury (SCI). This proposal was based on small, midline stab SCI. Here, we tested the generality of this proposal by using a genetic knock-in cell fate mapping strategy in different murine SCI models. After large crush injuries across the entire spinal cord, ependyma-derived progeny remained local, did not migrate and contributed few cells of any kind and less than 2%, if any, of the total newly proliferated and molecularly confirmed scar-forming astrocytes. Stab injuries that were near to but did not directly damage ependyma, contained no ependyma-derived cells. Our findings show that ependymal contribution of progeny after SCI is minimal, local and dependent on direct ependymal injury, indicating that ependyma are not a major source of endogenous neural stem cells or neuroprotective astrocytes after SCI. PMID:28117356
Ren, Yilong; Ao, Yan; O'Shea, Timothy M; Burda, Joshua E; Bernstein, Alexander M; Brumm, Andrew J; Muthusamy, Nagendran; Ghashghaei, H Troy; Carmichael, S Thomas; Cheng, Liming; Sofroniew, Michael V
Ependyma have been proposed as adult neural stem cells that provide the majority of newly proliferated scar-forming astrocytes that protect tissue and function after spinal cord injury (SCI). This proposal was based on small, midline stab SCI. Here, we tested the generality of this proposal by using a genetic knock-in cell fate mapping strategy in different murine SCI models. After large crush injuries across the entire spinal cord, ependyma-derived progeny remained local, did not migrate and contributed few cells of any kind and less than 2%, if any, of the total newly proliferated and molecularly confirmed scar-forming astrocytes. Stab injuries that were near to but did not directly damage ependyma, contained no ependyma-derived cells. Our findings show that ependymal contribution of progeny after SCI is minimal, local and dependent on direct ependymal injury, indicating that ependyma are not a major source of endogenous neural stem cells or neuroprotective astrocytes after SCI.
Hou, Ying-Nuo; Ding, Wen-Yuan; Shen, Yong; Yang, Da-Long; Wang, Lin-Feng; Zhang, Peng
To study the effect of hyperbaric oxygen intervention on the microenvironment of nerve regeneration after spinal cord injury modeling and to explore the possible mechanism of nerve regeneration and functional recovery in rats with spinal cord injury. In 98 adult female SD rats, 90 successful models were obtained, which were divided into sham group, spinal cord injury group and hyperbaric oxygen group using randomized block method, 30/group. Spinal cord injury rat model was established in accordance with the modified Allen method. Motor function was assessed at the time points of before modeling, one day, three days, one week, two weeks, three weeks and four weeks after modeling respectively by BBB rating, inclined plane test and improved Tarlov score. At 3 days after modeling, apoptosis of neuronal cells in spinal cord injury region in experimental group was detected by TUNEL method; gene and protein expression of MMP9/2 in spinal cord injury and surrounding tissues was detected by RT-PCR and Western blot assay. At 4 weeks after modeling, histopathological morphological changes in spinal cord injury were observed by HE staining; fluorogold retrograde tracing was used to observe the regeneration and distribution of spinal cord nerve fibers and axon regeneration was observed by TEM. The three motor function scores in hyperbaric oxygen group at each time point after two weeks of treatment were significantly increased compared with spinal cord injury group (P < 0.05). At 3 d after modeling, apoptosis index in hyperbaric oxygen group were significantly lower than those in spinal cord injury group (P < 0.05). At 72 h after modeling, compared with spinal cord injury group, MMP9/2 gene and protein expression in hyperbaric oxygen group was significantly lower (P < 0.05). At four weeks after modeling, fluorogold positive nerve fibers were the most sham group, followed by hyperbaric oxygen group and spinal cord injury group in order; the differences among the groups were
Li, Xi-gong; Lin, Xiang-jin; Du, Jun-hua; Xu, San-zhong; Lou, Xian-feng; Chen, Zhong
Methylprednisolone exhibits anti-inflammatory antioxidant properties, and rosiglitazone acts as an anti-inflammatory and antioxidant by activating peroxisome proliferator-activated receptor-γ in the spinal cord. Methylprednisolone and rosiglitazone have been clinically used during the early stages of secondary spinal cord injury. Because of the complexity and diversity of the inflammatory process after spinal cord injury, a single drug cannot completely inhibit inflammation. Therefore, we assumed that a combination of methylprednisolone and rosiglitazone might promote recovery of neurological function after secondary spinal cord injury. In this study, rats were intraperitoneally injected with methylprednisolone (30 mg/kg) and rosiglitazone (2 mg/kg) at 1 hour after injury, and methylprednisolone (15 mg/kg) at 24 and 48 hours after injury. Rosiglitazone was then administered once every 12 hours for 7 consecutive days. Our results demonstrated that a combined treatment with methylprednisolone and rosiglitazone had a more pronounced effect on attenuation of inflammation and cell apoptosis, as well as increased functional recovery, compared with either single treatment alone, indicating that a combination better promoted recovery of neurological function after injury. PMID:27904502
Kesherwani, V; Atif, F; Yousuf, S; Agrawal, S K
Damage from oxidative stress plays a critical role in spinal cord injury. Nuclear factor erythroid 2-related factor (Nrf-2) signaling pathway can be activated by cellular oxidative stress. Resveratrol, a plant-derived polyphenolic compound found in red wine, has antioxidant properties. In the present study, we have examined the neuroprotective effect of resveratrol and the role of Nrf-2 in spinal cord hypoxic injury. The spinal cord was removed from adult male Wistar rats from T2-T10 and the dorsal column was used to induce hypoxic injury in vitro with and without treatment with resveratrol (50μM). Significant changes were found in the compound action potential (CAP) of spinal cord dorsal column, and hematoxyline and eosin (H&E) staining showed that resveratrol significantly improved neuronal injury. The biochemical assays showed significant changes in lipid peroxidase (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), protein carbonyl (PC), mitochondrial ATP content, and mitochondrial Ca(++). Furthermore, using immunohistochemistry and Western blot, we found that after resveratrol treatment during hypoxic injury there was a significant activation of NrF-2 and down regulation of the glial fibrillary acidic protein (GFAP) content. The results show that resveratrol treatment has neuroprotective effects on CAP, Ca(++) loading, and biochemical parameters after hypoxic injury. The neuroprotective effect is likely to be exerted by increased activation of transcription factor Nrf-2 by resveratrol along with its direct antioxidant effect to ameliorate the oxidative damage and preserve mitochondrial function.
Anderson, Aileen J; Najbauer, Joseph; Huang, Wencheng; Young, Wise; Robert, Stephanie
We have previously described the activation of the classical, alternative, and terminal complement cascade pathways after acute contusion spinal cord injury using the New York University (NYU) weight-drop impactor. In the present study, we examined the induction of protein regulators of the complement cascade, factor H (FH), and clusterin, in the same experimental paradigm. The spinal cord of laminectomized adult rats was subjected to mild or severe injury using impactor weight-drop heights of 12.5 and 50 mm, respectively. The spinal cords of control and injured animals were evaluated at 1, 7, and 42 days after injury. Immunocytochemistry revealed a robust increase in the numbers and intensity of staining of FH, and clusterin-positive cells in the injured cord at all three time points, with the highest increases observed at 1 and 42 days after injury. FH and clusterin-positive cells were observed among neurons as well as oligodendrocytes. The increased expression was detected both rostrally and caudally from the injury site, in the latter case at distances up to 20 mm. The precise biological significance of injury-induced upregulation of these proteins remains to be determined. However, FH and clusterin are potent regulators of complement activity targeting upstream (FH) and downstream (clusterin) molecules of the pro-inflammatory cascade, which could be of vital importance in preventing a "runaway" inflammatory reaction in the injured spinal cord.
Ahmadzadeh, Gholamhossein; Kouchaki, Anahita; Malekian, Azadeh; Aminorro’aya, Mahin; Boroujeni, Ali Zargham
BACKGROUND: Spinal injury can establish severe psychological outcomes for the patient and his/her family which requires high adjustment. Health system staff would be able to play their roles well in caring these patients provided with knowing what steps spinal injured people should pass to handle their disability and also what assistance they need in what stages from what sources. This study aimed to explain the process of confrontation with disability in spinal cord injured patients. METHODS: This was a qualitative study with grounded theory approach which was performed in Strauss and Corbin proposed method on twenty people with spinal cord injury who had past at least three months from their spinal injury. Sampling was done in purposive and theoretical method, and analysis of the results was also performed during constant comparative process. RESULTS: Central concept in the data was support which was associated with other concepts and affected them. The patients, with the help of internal and external support could overcome their main problem that was disability feeling and dependency on others and find a new definition for the self, and ultimately achieve the sense of independence and autonomy. CONCLUSIONS: Knowing the process of confrontation with disability along with better understanding of spinal cord injured people would help health system staff to actualize and support their potentials much better through strengthening internal resources and providing appropriate supportive services of each individual. PMID:22069411
Palejwala, Ali H.; Fridley, Jared S.; Mata, Javier A.; Samuel, Errol L. G.; Luerssen, Thomas G.; Perlaky, Laszlo; Kent, Thomas A.; Tour, James M.; Jea, Andrew
Background: Graphene has unique electrical, physical, and chemical properties that may have great potential as a bioscaffold for neuronal regeneration after spinal cord injury. These nanoscaffolds have previously been shown to be biocompatible in vitro; in the present study, we wished to evaluate its biocompatibility in an in vivo spinal cord injury model. Methods: Graphene nanoscaffolds were prepared by the mild chemical reduction of graphene oxide. Twenty Wistar rats (19 male and 1 female) underwent hemispinal cord transection at approximately the T2 level. To bridge the lesion, graphene nanoscaffolds with a hydrogel were implanted immediately after spinal cord transection. Control animals were treated with hydrogel matrix alone. Histologic evaluation was performed 3 months after the spinal cord transection to assess in vivo biocompatibility of graphene and to measure the ingrowth of tissue elements adjacent to the graphene nanoscaffold. Results: The graphene nanoscaffolds adhered well to the spinal cord tissue. There was no area of pseudocyst around the scaffolds suggestive of cytotoxicity. Instead, histological evaluation showed an ingrowth of connective tissue elements, blood vessels, neurofilaments, and Schwann cells around the graphene nanoscaffolds. Conclusions: Graphene is a nanomaterial that is biocompatible with neurons and may have significant biomedical application. It may provide a scaffold for the ingrowth of regenerating axons after spinal cord injury. PMID:27625885
Tsintou, Magdalini; Dalamagkas, Kyriakos; Seifalian, Alexander Marcus
Spinal cord injury results in the permanent loss of function, causing enormous personal, social and economic problems. Even though neural regeneration has been proven to be a natural mechanism, central nervous system repair mechanisms are ineffective due to the imbalance of the inhibitory and excitatory factors implicated in neuroregeneration. Therefore, there is growing research interest on discovering a novel therapeutic strategy for effective spinal cord injury repair. To this direction, cell-based delivery strategies, biomolecule delivery strategies as well as scaffold-based therapeutic strategies have been developed with a tendency to seek for the answer to a combinatorial approach of all the above. Here we review the recent advances on regenerative/neural engineering therapies for spinal cord injury, aiming at providing an insight to the most promising repair strategies, in order to facilitate future research conduction. PMID:26109946
Hu, Chunying; Ye, Miao; Huang, Qiuchen
[Purpose] The purpose of this study was to observe the effects of manual therapy on bowel function of patients with spinal cord injury. [Subjects] The participants were 20 patients with spinal cord injury. [Methods] Manual therapy was applied to the intestine and along the colon ascendens, transverse colon, colon descendens and colon sigmoidem on the surface of abdomen. The results before and after 60 sessions (5 times/week, continued for 12 weeks) of manual therapy were compared. [Results] It was found that there were significant effects both on shortening of bowel time and decreasing dosage of glycerine enema every time patients needed to excrete. [Conclusion] Manual therapy had significant effects on bowel function of patients with spinal cord injury.
In the last century, research in the field of spinal cord trauma has brought insightful knowledge which has led to a detailed understanding of mechanisms that are involved in injury- and recovery-related processes. The quest for a cure for the yet generally incurable condition as well as the exponential rise in gained information has brought about the development of numerous treatment approaches while at the same time the abundance of data has become quite unmanageable. Owing to an enormous amount of preclinical therapeutic approaches, this report highlights important trends rather than specific treatment strategies. We focus on current advances in the treatment of spinal cord injury and want to further draw attention to arising problems in spinal cord injury (SCI) research and discuss possible solutions. PMID:25343041
Tang, Ying; Allen, Victoria; DeVivo, Michael J.
Background: Despite a consistent trend toward older age at time of spinal cord injury (SCI), little is known about the external causes of SCI in the elderly. Objective: To examine environmental circumstances, documented by International Classification of Diseases, 10th Revision, Clinical Modification codes, at time of SCI among older adults. Method: Data on individuals injured in 2005 or later were retrieved from the National SCI Database. Demographics, injury profiles, and external causes of injury were compared between the study group (age >60 years, n = 1,079) and reference group (age 16–45 years, n = 3,579) using chi-square and Student t tests. Results: Among the elderly, falls were the most common etiology of SCI (60%), followed by transport accidents (24%) and complications of medical and surgical care (12%). In the younger group, transport accidents were the most common etiology of SCI (49%), followed by falls (22%) and assault (21%). Falls on the same level (30%), from stairs and steps (22%), and other slipping, tripping, and stumbling (11%) were the most common mechanisms of falls in the elderly group. Among motor vehicle accidents, car occupant injured in a collision with another car was the most common mechanism of injury among the elderly (28%). Conclusion: There is an urgent need for effective fall prevention programs among the elderly to reduce SCI in this expanding population. Details on the mechanisms of falls and other major causes of SCI among the elderly provided in this study should inform the development of future interventions for high-risk persons, activities, and environments. PMID:26363588
Wu, Y; Satkunendrarajah, K; Fehlings, M G
The spinal cord is vulnerable to ischemic injury due to trauma, vascular malformations and correction of thoracic aortic lesions. Riluzole, a sodium channel blocker and anti-glutamate drug has been shown to be neuroprotective in a model of ischemic spinal cord injury, although the effects in clinically relevant ischemia/reperfusion models are unknown. Here, we examine the effect of riluzole following ischemia-reperfusion injury to the spinal cord. Female rats underwent high thoracic aortic balloon occlusion to produce an ischemia/reperfusion injury. Tolerance to ischemia was evaluated by varying the duration of occlusion. Riluzole (8mg/kg) was injected intraperitoneally 4h after injury. Locomotor function (Basso, Beattie and Bresnahan (BBB) scale) was assessed at 4h, 1day, and 5days post-ischemia. Spinal cords were extracted and evaluated for neuronal loss using immunohistology (choline acetyltransferase (ChAT) and neuronal nuclei (NeuN)), inflammation (CD11b), astrogliosis (glial fibrillary acidic protein - GFAP) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Ischemic injury lasting between 5.5 and 6.75min resulted in delayed paraplegia, whereas longer ischemia induced immediate paraplegia. When riluzole was administered to rats that underwent 6min of occlusion, delayed paraplegia was prevented. The BBB score of riluzole-treated rats was 11.14±4.85 compared with 1.86±1.07 in control animals. Riluzole also reduced neuronal loss, infiltration of microglia/macrophages and astrogliosis in the ventral horn and intermediate zone of the gray matter. In addition, riluzole reduced apoptosis of neurons in the dorsal horn of the gray matter. Riluzole has a neuroprotective effect in a rat model of spinal cord injury/reperfusion when administered up to 4h post-injury, a clinically relevant therapeutic time window.
Beauparlant, Janine; van den Brand, Rubia; Barraud, Quentin; Friedli, Lucia; Musienko, Pavel; Dietz, Volker; Courtine, Grégoire
Severe spinal cord injury in humans leads to a progressive neuronal dysfunction in the chronic stage of the injury. This dysfunction is characterized by premature exhaustion of muscle activity during assisted locomotion, which is associated with the emergence of abnormal reflex responses. Here, we hypothesize that undirected compensatory plasticity within neural systems caudal to a severe spinal cord injury contributes to the development of neuronal dysfunction in the chronic stage of the injury. We evaluated alterations in functional, electrophysiological and neuromorphological properties of lumbosacral circuitries in adult rats with a staggered thoracic hemisection injury. In the chronic stage of the injury, rats exhibited significant neuronal dysfunction, which was characterized by co-activation of antagonistic muscles, exhaustion of locomotor muscle activity, and deterioration of electrochemically-enabled gait patterns. As observed in humans, neuronal dysfunction was associated with the emergence of abnormal, long-latency reflex responses in leg muscles. Analyses of circuit, fibre and synapse density in segments caudal to the spinal cord injury revealed an extensive, lamina-specific remodelling of neuronal networks in response to the interruption of supraspinal input. These plastic changes restored a near-normal level of synaptic input within denervated spinal segments in the chronic stage of injury. Syndromic analysis uncovered significant correlations between the development of neuronal dysfunction, emergence of abnormal reflexes, and anatomical remodelling of lumbosacral circuitries. Together, these results suggest that spinal neurons deprived of supraspinal input strive to re-establish their synaptic environment. However, this undirected compensatory plasticity forms aberrant neuronal circuits, which may engage inappropriate combinations of sensorimotor networks during gait execution.
Erschbamer, M K; Pham, T M; Zwart, M C; Baumans, V; Olson, L
Environmental enrichment and exercise may be neuroprotective or promote recovery after different forms of CNS injury. Here, we tested the possible effects of moderate environmental enrichment and voluntary exercise on the outcome of incomplete spinal cord injury in rats. We provided rats in standard cages with basic environmental enrichment (carton house, nesting material, tube, gnawing sticks). We also analyzed the effect of increased activity by housing spinal-cord-injured rats in cages with or without access to running wheels. In a third experiment, we looked at the possible effect of pre-injury training. In all experiments, a battery of behavior tests were used. Enriched environment provided before, after or both before and after injury did not alter the outcome on any of these tests. Similarly, despite excessive running after injury, no differences in terms of recovery and behavior were found in the running experiment. Similarly, running prior to injury did not significantly decrease the degree of functional deficit caused by the injury. Since there were no effects of further enrichment, above the possible effects of being socially housed, and since exercise did not improve the outcome, we conclude that these forms of increased activity do not render the animals significantly less sensitive to spinal cord injury and do not cause robust improvement when initiated after injury. While these results pose a limit to how helpful environmental and physical training programs may be in rodent impact injury models, they do not contradict the fact that voluntary and guided training can be effective tools in human spinal cord rehabilitation.
Wilson, Lisa; Catalano, Denise; Sung, Connie; Phillips, Brian; Chou, Chih-Chin; Chan, Jacob Yui Chung; Chan, Fong
Objective: To examine the roles of attachment, social support, and coping as psychosocial correlates in predicting happiness in people with spinal cord injuries. Design: Quantitative descriptive research design using multiple regression and correlation techniques. Participants: 274 individuals with spinal cord injuries. Outcome Measures: Happiness…
Smedema, Susan Miller; Pfaller, Joseph; Moser, Erin; Tu, Wei-Mo; Chan, Fong
Objective: To evaluate the measurement structure of the Trait Hope Scale (THS) among individuals with spinal cord injury. Design: Confirmatory factor analysis and reliability and validity analyses were performed. Participants: 242 individuals with spinal cord injury. Results: Results support the two-factor measurement model for the THS with agency…
Lustig, Daniel C.
This study investigated the relationship between perceived changes in sense of coherence from pre- to postinjury and adjustment for a group of individuals with spinal cord injury. It was hypothesized that after a spinal cord injury, an individual's belief that he or she had significantly reduced his or her sense of coherence would be associated…
Yousefifard, Mahmoud; Rahimi-Movaghar, Vafa; Baikpour, Masoud; Ghelichkhani, Parisa; Hosseini, Mostafa; Jafari, AliMoghadas; Aziznejad, Heidar; Tafakhori, Abbas
Introduction: Despite the vast number of surveys, no consensus has been reached on the optimum timing of spinal decompression surgery. This systematic review and meta-analysis aimed to compare the effects of early and latespinal decompression surgery on neurologic improvement and post-surgical complications in patients with traumatic spinal cord injuries. Methods: Two independent reviewers carried out an extended search in electronic databases. Data of neurological outcome and post-surgery complication were extracted. Finally, pooled relative risk (RR) with a 95% confidence interval (CI) was reported for comparing of efficacy of early and late surgical decompression. Results: Eventually 22 studies were included. The pooled RRwas 0.77 (95% CI: 0.68-0.89)for at least one grade neurological improvement, and 0.84 (95% CI: 0.77-0.92)for at least two grade improvement. Pooled RR for surgical decompression performed within 12 hours after the injury was 0.26 (95% CI: 0.13-0.52; p<0.001), while it was 0.75 (95% CI: 0.63-0.90; p=0.002) when the procedure was performed within 24 hours, and 0.93 (95% CI: 0.76-1.14; p=0.48) when it was carried out in the first 72 hours after the injury. Surgical decompression performed within 24 hours after injury was found to be associated with significantly lower rates of post-surgical complications (RR=0.77; 95% CI: 0.68-0.86; p<0.001). Conclusion: The findings of this study indicate that early spinal decompression surgery can improve neurologic recovery and is associated with less post-surgical complications. The optimum efficacy is observed when the procedure is performed within 12 hours of the injury. PMID:28286844
Chen, Yu-Bing; Jia, Quan-Zhang; Li, Dong-Jun; Sun, Jing-Hai; Xi, Shuang; Liu, Li-Ping; Gao, De-Xuan; Jiang, Da-Wei
The aim of this study was to observe the effects of bone marrow mesenchymal stem-cell transplantation (BMSCs) in repairing acute spinal cord damage in rats and to examine the potential beneficial effects. 192 Wistar rats were randomized into 8 groups. Spinal cord injury was created. Behavior and limb functions were scored. Repairing effects of BMSCs transplantation was evaluated and compared. In vitro 4',6-diamidino-2-phenylindole (DAPI)-tagged BMSCs were observed, and whether they migrated to the area of spinal cord injury after intravenous tail injection was investigated. The expression of neuron-specific protein (NSE) on BMSCs was examined. Fifteen days after transplantation, the BMSCs-treated groups scored significantly higher in limb function tests than the untreated group. Pathological sections of the bone marrow after operation showed significant recovery in treated groups in comparison to the control group. After transplantation, small amounts of fluorescent-tagged BMSCs can be found in the blood vessels in the area of spinal cord injury, and fluorescent-tagged BMSCs were diffused in extravascular tissues, whereas the DAPI-tagged BMSCs could not be detected,and BrdU/NSE double-labeled cells were found in the injured marrow. BMSCs improve behavioral responses and can repair spinal cord injuries by migrating to the injured area, where they can differentiate into neurons.
Roelcke, U; Curt, A; Otte, A; Missimer, J; Maguire, R P; Dietz, V; Leenders, K L
OBJECTIVES: To assess the effect of a transverse spinal cord lesion on cerebral energy metabolism in view of sensorimotor reorganisation. METHODS: PET and 18F-fluorodeoxyglucose were used to study resting cerebral glucose metabolism in 11 patients with complete paraplegia or tetraplegia after spinal cord injury and 12 healthy subjects. Regions of interest analysis was performed to determine global glucose metabolism (CMRGlu). Statistical parametric mapping was applied to compare both groups on a pixel by pixel basis (significance level P = 0.001). RESULTS: Global absolute CMRGlu was lower in spinal cord injury (33.6 (6.6) mumol/100 ml/min (mean (SD)) than in controls (45.6 (6.2), Mann-Whitney P = 0.0026). Statistical parametric mapping analysis disclosed relatively increased glucose metabolism particularly in the supplementary motor area, anterior cingulate, and putamen. Relatively reduced glucose metabolism in patients with spinal cord injury was found in the midbrain, cerebellar hemispheres, and temporal cortex. CONCLUSIONS: It is assumed that cerebral deafferentiation due to reduction or loss of sensorimotor function results in the low level of absolute global CMRGlu found in patients with spinal cord injury. Relatively increased glucose metabolism in brain regions involved in attention and initiation of movement may be related to secondary disinhibition of these regions. PMID:9010401
Flynn, Jamie R.; Dunn, Lynda R.; Galea, Mary P.; Callister, Robin; Rank, Michelle M.
Abstract Following spinal cord injury (SCI), anatomical changes such as axonal sprouting occur within weeks in the vicinity of the injury. Exercise training enhances axon sprouting; however, the exact mechanisms that mediate exercised-induced plasticity are unknown. We studied the effects of exercise training after SCI on the intrinsic and synaptic properties of spinal neurons in the immediate vicinity (<2 segments) of the SCI. Male mice (C57BL/6, 9–10 weeks old) received a spinal hemisection (T10) and after 1 week of recovery, they were randomized to trained (treadmill exercise for 3 weeks) and untrained (no exercise) groups. After 3 weeks, mice were killed and horizontal spinal cord slices (T6–L1, 250 μm thick) were prepared for visually guided whole cell patch clamp recording. Intrinsic properties, including resting membrane potential, input resistance, rheobase current, action potential (AP) threshold and after-hyperpolarization (AHP) amplitude were similar in neurons from trained and untrained mice (n=67 and 70 neurons, respectively). Neurons could be grouped into four categories based on their AP discharge during depolarizing current injection; the proportions of tonic firing, initial bursting, single spiking, and delayed firing neurons were similar in trained and untrained mice. The properties of spontaneous excitatory synaptic currents (sEPSCs) did not differ in trained and untrained animals. In contrast, evoked excitatory synaptic currents recorded after dorsal column stimulation were markedly increased in trained animals (peak amplitude 78.9±17.5 vs. 42.2±6.8 pA; charge 1054±376 vs. 348±75 pA·ms). These data suggest that 3 weeks of treadmill exercise does not affect the intrinsic properties of spinal neurons after SCI; however, excitatory synaptic drive from dorsal column pathways, such as the corticospinal tract, is enhanced. PMID:23320512
Evaniew, Nathan; Noonan, Vanessa K.; Fallah, Nader; Kwon, Brian K.; Rivers, Carly S.; Ahn, Henry; Bailey, Christopher S.; Christie, Sean D.; Fourney, Daryl R.; Hurlbert, R. John; Linassi, A.G.; Fehlings, Michael G.
Abstract In prior analyses of the effectiveness of methylprednisolone for the treatment of patients with acute traumatic spinal cord injuries (TSCIs), the prognostic importance of patients' neurological levels of injury and their baseline severity of impairment has not been considered. Our objective was to determine whether methylprednisolone improved motor recovery among participants in the Rick Hansen Spinal Cord Injury Registry (RHSCIR). We identified RHSCIR participants who received methylprednisolone according to the Second National Spinal Cord Injury Study (NASCIS-II) protocol and used propensity score matching to account for age, sex, time of neurological exam, varying neurological level of injury, and baseline severity of neurological impairment. We compared changes in total, upper extremity, and lower extremity motor scores using the Wilcoxon signed-rank test and performed sensitivity analyses using negative binomial regression. Forty-six patients received methylprednisolone and 1555 received no steroid treatment. There were no significant differences between matched participants for each of total (13.7 vs. 14.1, respectively; p=0.43), upper extremity (7.3 vs. 6.4; p=0.38), and lower extremity (6.5 vs. 7.7; p=0.40) motor recovery. This result was confirmed using a multivariate model and, as predicted, only cervical (C1–T1) rather than thoracolumbar (T2–L3) injury levels (p<0.01) and reduced baseline injury severity (American Spinal Injury Association [ASIA] Impairment Scale grades; p<0.01) were associated with greater motor score recovery. There was no in-hospital mortality in either group; however, the NASCIS-II methylprednisolone group had a significantly higher rate of total complications (61% vs. 36%; p=0.02) NASCIS-II methylprednisolone did not improve motor score recovery in RHSCIR patients with acute TSCIs in either the cervical or thoracic spine when the influence of anatomical level and severity of injury were included in the analysis. There
Kirshblum, Steven; Waring, William
The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) is the most widely used classification in the field of spinal cord injury medicine. Since its first publication in 1982, multiple revisions refining the recommended examination, scaling, and classification have taken place to improve communication, consistency, and clarity. This article describes a brief historical perspective on the development and changes over the years leading to the current ISNCSCI, detailing the most recent updates of 2011 and the worksheet 2013 as well as issues facing the ISNCSCI for the future.
Graillon, T; Pech-Gourg, G; Adetchessi, T; Metellus, P; Dufour, H; Fuentes, S
Klippel-Feil syndrome (KFS) is defined as a congenital fusion of at least two cervical vertebrae. Patients with KFS are known to be at high risk for spinal cord injury in case of cervical trauma even with weak kinetic. We report the case of a patient with C4-C5 and C6-C7 congenital fusion, harbouring C5-C6 post-traumatic spinal cord injury, associated with an odontoid fracture type 2 of Anderson and D'Alonzo classification following a motorbike accident.
Kim, Christopher; Vassilyadi, Michael; Forbes, Jason K.; Moroz, Nicholas W.P.; Camacho, Alexandra; Moroz, Paul J.
Background With a reported incidence of up to 10% compared to all spinal trauma, spinal injuries in children are less common than in adults. Children can have spine fractures with or without myelopathy, or spinal cord injuries without radiological abnormalities (SCIWORA). Methods We retrospectively reviewed the cases of children with spinal injuries treated at a level 1 pediatric trauma centre between 1990 and 2013. Results A total of 275 children were treated during the study period. The mean age at admission was 12 ± 4.5 years, and the male:female ratio was 1.4:1. Spinal injuries were more common in children of ages 12–16 years, with most injuries among ages 15–16 years. The top 3 mechanisms of spinal injury were motor vehicle–related trauma (53%), sports (28%) and falls (13%). Myelopathy occurred in 12% and SCIWORA occurred in 6%. The most common spine levels injured were L2–sacrum, followed by O–C2. Associated injuries, including head injuries (29%), and fractures/dislocations (27%) occurred in 55% of children. Overall mortality was 3%. Surgical intervention was required in 14%. Conclusion The creation of a pediatric spinal injury database using this 23-year retrospective review helped identify important clinical concepts; we found that active adolescent boys had the highest risk of spine injury, that noncontiguous spine injuries occured at a rate higher than reported previously and that nonaccidental spine injuries in children are under-reported. Our findings also emphasize the importance of maintaining a higher index of suspicion with trauma patients with multiple injuries and of conducting detailed clinical and radiographic examinations of the entire spine in children with a known spinal injury. PMID:27240286
Liu, Jian; Yang, Xiao-yu; Xia, Wei-wei; Dong, Jian; Yang, Mao-guang; Jiao, Jian-hang
Following central nervous system injury, axonal sprouts form distal to the injury site and extend into the denervated area, reconstructing neural circuits through neural plasticity. How to facilitate this plasticity has become the key to the success of central nervous system repair. It remains controversial whether fine motor skill training contributes to the recovery of neurological function after spinal cord injury. Therefore, we established a rat model of unilateral corticospinal tract injury using a pyramidal tract cutting method. Horizontal ladder crawling and food ball grasping training procedures were conducted 2 weeks before injury and 3 days after injury. The neurological function of rat forelimbs was assessed at 1, 2, 3, 4, and 6 weeks after injury. Axon growth was observed with biotinylated dextran amine anterograde tracing in the healthy corticospinal tract of the denervated area at different time periods. Our results demonstrate that compared with untrained rats, functional recovery was better in the forelimbs and forepaws of trained rats. The number of axons and the expression of growth associated protein 43 were increased at the injury site 3 weeks after corticospinal tract injury. These findings confirm that fine motor skill training promotes central nervous system plasticity in spinal cord injury rats. PMID:28197197
Heinemann, Allen W.; Magasi, Susan; Hammel, Joy; Carlozzi, Noelle E.; Garcia, Sofia F.; Hahn, Elizabeth A.; Lai, Jin-Shei; Tulsky, David; Gray, David B.; Hollingsworth, Holly; Jerousek, Sara
Objectives To describe methods used in operationalizing environmental factors; to describe the results of a research project to develop measures of environmental factors that affect participation; and to define an initial item set of facilitators and barriers to participation after stroke, traumatic brain injury, and spinal cord injury. Design Instrument development included an extensive literature review, item classification and selection, item writing, and cognitive testing following the approach of the Patient-Reported Outcomes Measurement Information System. Setting Community. Participants Content area and outcome measurement experts (n=10) contributed to instrument development; individuals (n=200) with the target conditions participated in focus groups and in cognitive testing (n=15). Interventions None. Main Outcome Measures Environmental factor items were categorized in 6 domains: assistive technology; built and natural environment; social environment; services, systems, and policies; access to information and technology; and economic quality of life. Results We binned 2273 items across the 6 domains, winnowed this pool to 291 items for cognitive testing, and recommended 274 items for pilot data collection. Conclusions Five of the 6 domains correspond closely to the International Classification of Functioning, Disability and Health taxonomy of environmental factors; the sixth domain, economic quality of life, reflects an important construct that reflects financial resources that affect participation. Testing with a new and larger sample is underway to evaluate reliability, validity, and sensitivity. PMID:24378804
Brotfain, Evgeni; Gruenbaum, Shaun E.; Boyko, Matthew; Kutz, Ruslan; Zlotnik, Alexander; Klein, Moti
In recent years there has been a growing body of clinical and laboratory evidence demonstrating the neuroprotective effects of estrogen and progesterone after traumatic brain injury (TBI) and spinal cord injury (SCI). In humans, women have been shown to have a lower incidence of morbidity and mortality after TBI compared with age-matched men. Similarly, numerous laboratory studies have demonstrated that estrogen and progesterone administration is associated with a mortality reduction, improvement in neurological outcomes, and a reduction in neuronal apoptosis after TBI and SCI. Here, we review the evidence that supports hormone-related neuroprotection and discuss possible underlying mechanisms. Estrogen and progesterone-mediated neuroprotection are thought to be related to their effects on hormone receptors, signaling systems, direct antioxidant effects, effects on astrocytes and microglia, modulation of the inflammatory response, effects on cerebral blood flow and metabolism, and effects on mediating glutamate excitotoxicity. Future laboratory research is needed to better determine the mechanisms underlying the hormones’ neuroprotective effects, which will allow for more clinical studies. Furthermore, large randomized clinical control trials are needed to better assess their role in human neurodegenerative conditions. PMID:26955967
Hayes, Heather B.; Jayaraman, Arun; Herrmann, Megan; Mitchell, Gordon S.; Rymer, William Z.
Objectives: To test the hypothesis that daily acute intermittent hypoxia (dAIH) and dAIH combined with overground walking improve walking speed and endurance in persons with chronic incomplete spinal cord injury (iSCI). Methods: Nineteen subjects completed the randomized, double-blind, placebo-controlled, crossover study. Participants received 15, 90-second hypoxic exposures (dAIH, fraction of inspired oxygen [Fio2] = 0.09) or daily normoxia (dSHAM, Fio2 = 0.21) at 60-second normoxic intervals on 5 consecutive days; dAIH was given alone or combined with 30 minutes of overground walking 1 hour later. Walking speed and endurance were quantified using 10-Meter and 6-Minute Walk Tests. The trial is registered at ClinicalTrials.gov (NCT01272349). Results: dAIH improved walking speed and endurance. Ten-Meter Walk time improved with dAIH vs dSHAM after 1 day (mean difference [MD] 3.8 seconds, 95% confidence interval [CI] 1.1–6.5 seconds, p = 0.006) and 2 weeks (MD 3.8 seconds, 95% CI 0.9–6.7 seconds, p = 0.010). Six-Minute Walk distance increased with combined dAIH + walking vs dSHAM + walking after 5 days (MD 94.4 m, 95% CI 17.5–171.3 m, p = 0.017) and 1-week follow-up (MD 97.0 m, 95% CI 20.1–173.9 m, p = 0.014). dAIH + walking increased walking distance more than dAIH after 1 day (MD 67.7 m, 95% CI 1.3–134.1 m, p = 0.046), 5 days (MD 107.0 m, 95% CI 40.6–173.4 m, p = 0.002), and 1-week follow-up (MD 136.0 m, 95% CI 65.3–206.6 m, p < 0.001). Conclusions: dAIH ± walking improved walking speed and distance in persons with chronic iSCI. The impact of dAIH is enhanced by combination with walking, demonstrating that combinatorial therapies may promote greater functional benefits in persons with iSCI. Classification of evidence: This study provides Class I evidence that transient hypoxia (through measured breathing treatments), along with overground walking training, improves walking speed and endurance after iSCI. PMID:24285617
Mateo, Sébastien; Roby-Brami, Agnès; Reilly, Karen T; Rossetti, Yves; Collet, Christian; Rode, Gilles
Although a number of upper limb kinematic studies have been conducted, no review actually addresses the key-features of open-chain upper limb movements after cervical spinal cord injury (SCI). The aim of this literature review is to provide a clear understanding of motor control and kinematic changes during open-chain upper limb reaching, reach-to-grasp, overhead movements, and fast elbow flexion movements after tetraplegia. Using data from MEDLINE between 1966 and December 2014, we examined temporal and spatial kinematic measures and when available electromyographic recordings. We included fifteen control case and three series case studies with a total of 164 SCI participants and 131 healthy control participants. SCI participants efficiently performed a broad range of tasks with their upper limb and movements were planned and executed with strong kinematic invariants like movement endpoint accuracy and minimal cost. Our review revealed that elbow extension without triceps brachii relies on increased scapulothoracic and glenohumeral movements providing a dynamic coupling between shoulder and elbow. Furthermore, contrary to normal grasping patterns where grasping is prepared during the transport phase, reaching and grasping are performed successively after SCI. The prolonged transport phase ensures correct hand placement while the grasping relies on wrist extension eliciting either whole hand or lateral grip. One of the main kinematic characteristics observed after tetraplegia is motor slowing attested by increased movement time. This could be caused by (i) decreased strength, (ii) triceps brachii paralysis which disrupts normal agonist-antagonist co-contractions, (iii) accuracy preservation at movement endpoint, and/or (iv) grasping relying on tenodesis. Another feature is a reduction of maximal superior reaching during overhead movements which could be caused by i) strength deficit in agonist muscles like pectoralis major, ii) strength deficit in proximal synergic
Bascom, Amy T; Sankari, Abdulghani; Goshgarian, Harry G; Badr, M Safwan
A high prevalence of sleep-disordered breathing (SDB) after spinal cord injury (SCI) has been reported in the literature; however, the underlying mechanisms are not well understood. We sought to determine the effect of the withdrawal of the wakefulness drive to breathe on the degree of hypoventilation in SCI patients and able-bodied controls. We studied 18 subjects with chronic cervical and thoracic SCI (10 cervical, 8 thoracic SCI; 11 males; age 42.4 ± 17.1 years; body mass index 26.3 ± 4.8 kg/m2) and 17 matched able-bodied subjects. Subjects underwent polysomnography, which included quantitative measurement of ventilation, timing, and upper airway resistance (RUA) on a breath-by-breath basis during transitions from wake to stage N1 sleep. Compared to able-bodied controls, SCI subjects had a significantly greater reduction in tidal volume during the transition from wake to N1 sleep (from 0.51 ± 0.21 to 0.32 ± 0.10 L vs. 0.47 ± 0.13 to 0.43 ± 0.12 L; respectively, P < 0.05). Moreover, end-tidal CO2 and end-tidal O2 were significantly altered from wake to sleep in SCI (38.9 ± 2.7 mmHg vs. 40.6 ± 3.4 mmHg; 94.1 ± 7.1 mmHg vs. 91.2 ± 8.3 mmHg; respectively, P < 0.05), but not in able-bodied controls (39.5 ± 3.2 mmHg vs. 39.9 ± 3.2 mmHg; 99.4 ± 5.4 mmHg vs. 98.9 ± 6.1 mmHg; respectively, P = ns). RUA was not significantly altered in either group. In conclusion, individuals with SCI experience hypoventilation at sleep onset, which cannot be explained by upper airway mechanics. Sleep onset hypoventilation may contribute to the development SDB in the SCI population. PMID:26290534
D'Amico, Jessica M.; Murray, Katherine C.; Li, Yaqing; Chan, K. Ming; Finlay, Mark G.; Bennett, David J.
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
Coulibaly, Aminata P; Isaacson, Lori G
Following injury to motor axons in the periphery, retrograde influences from the injury site lead to glial cell plasticity in the vicinity of the injured neurons. Following the transection of peripherally located preganglionic axons of the cervical sympathetic trunk (CST), a population of oligodendrocyte (OL) lineage cells expressing full length TrkB, the cognate receptor for brain derived neurotrophic factor (BDNF), is significantly increased in number in the spinal cord. Such robust plasticity in OL lineage cells in the spinal cord following peripheral axon transection led to the hypothesis that the gap junction communication protein connexin 32 (Cx32), which is specific to OL lineage cells, was influenced by the injury. Following CST transection, Cx32 expression in the spinal cord intermediolateral cell column (IML), the location of the parent cell bodies, was significantly increased. The increased Cx32 expression was localized specifically to TrkB OLs in the IML, rather than other cell types in the OL cell lineage, with the population of Cx32/TrkB cells increased by 59%. Cx32 expression in association with OPCs was significantly decreased at one week following the injury. The results of this study provide evidence that peripheral axon injury can differentially affect the gap junction protein expression in OL lineage cells in the adult rat spinal cord. We conclude that the retrograde influences originating from the peripheral injury site elicit dramatic changes in the CNS expression of Cx32, which in turn may mediate the plasticity of OL lineage cells observed in the spinal cord following peripheral axon injury.
Niedeggen, Andreas; Estel, Barbara; Seidl, Rainer O.
Objective To investigate risk factors for pneumonia in patients with traumatic lower cervical spinal cord injury. Design Observational study, retrospective study. Setting Spinal cord unit in a maximum care hospital. Methods Thirty-seven patients with acute isolated traumatic spinal cord injury at levels C4–C8 and complete motor function injury (AIS A, B) treated from 2004 to 2010 met the criteria for inclusion in our retrospective analysis. The following parameters were considered: ventilation-specific parameters, re-intubation, creation of a tracheostomy, pneumonia, antibiotic treatment, and length of intensive care unit (ICU) stay and total hospitalization. Results Among the patients, 81% had primary invasive ventilation. In 78% of cases a tracheostomy was created; 3% of these cases were discharged with invasive ventilation and 28% with a tracheostomy without ventilation. Pneumonia according to Centers for Disease Control criteria occurred in 51% of cases within 21 ± 32 days of injury, and in 3% at a later date. The number of pre-existing conditions was significantly associated with pneumonia. Length of ICU stay was 25 ± 34 days, and average total hospital duration was 230 ± 144 days. Significant factors affecting the duration of ventilation were the number of pre-existing conditions and tetraplegia-specific complications. Conclusions Our results confirm that patients with traumatic lower cervical spinal cord injuries defined by lesion level and AIS constitute a homogeneous group. This group is characterized by a high rate of pneumonia during the first 4 weeks after injury. The number of pre-existing general conditions and spinal injury-specific comorbidities are the only risk factors identified for the development of pneumonia and/or duration of ventilation. PMID:25117865
Yu, Shukui; Yao, Shenglian; Wen, Yujun; Wang, Ying; Wang, Hao; Xu, Qunyuan
This study examined sustained co-delivery of vascular endothelial growth factor (VEGF), angiopoietin-1 and basic fibroblast growth factor (bFGF) encapsulated in angiogenic microspheres. These spheres were delivered to sites of spinal cord contusion injury in rats, and their ability to induce vessel formation, neural regeneration and improve hindlimb motor function was assessed. At 2–8 weeks after spinal cord injury, ELISA-determined levels of VEGF, angiopoietin-1, and bFGF were significantly higher in spinal cord tissues in rats that received angiogenic microspheres than in those that received empty microspheres. Sites of injury in animals that received angiogenic microspheres also contained greater numbers of isolectin B4-binding vessels and cells positive for nestin or β III-tubulin (P < 0.01), significantly more NF-positive and serotonergic fibers, and more MBP-positive mature oligodendrocytes. Animals receiving angiogenic microspheres also suffered significantly less loss of white matter volume. At 10 weeks after injury, open field tests showed that animals that received angiogenic microspheres scored significantly higher on the Basso-Beattie-Bresnahan scale than control animals (P < 0.01). Our results suggest that biodegradable, biocompatible PLGA microspheres can release angiogenic factors in a sustained fashion into sites of spinal cord injury and markedly stimulate angiogenesis and neurogenesis, accelerating recovery of neurologic function. PMID:27641997
Gustin, S M; Wrigley, P J; Youssef, A M; McIndoe, L; Wilcox, S L; Rae, C D; Edden, R A E; Siddall, P J; Henderson, L A
There is increasing evidence relating thalamic changes to the generation and/or maintenance of neuropathic pain. We have recently reported that neuropathic orofacial pain is associated with altered thalamic anatomy, biochemistry, and activity, which may result in disturbed thalamocortical oscillatory circuits. Despite this evidence, it is possible that these thalamic changes are not responsible for the presence of pain per se, but result as a consequence of the injury. To clarify this subject, we compared brain activity and biochemistry in 12 people with below-level neuropathic pain after complete thoracic spinal cord injury with 11 people with similar injuries and no neuropathic pain and 21 age- and gender-matched healthy control subjects. Quantitative arterial spinal labelling was used to measure thalamic activity, and magnetic resonance spectroscopy was used to determine changes in neuronal variability quantifying N-acetylaspartate and alterations in inhibitory function quantifying gamma amino butyric acid. This study revealed that the presence of neuropathic pain is associated with significant changes in thalamic biochemistry and neuronal activity. More specifically, the presence of neuropathic pain after spinal cord injury is associated with significant reductions in thalamic N-acetylaspartate, gamma amino butyric acid content, and blood flow in the region of the thalamic reticular nucleus. Spinal cord injury on its own did not account for these changes. These findings support the hypothesis that neuropathic pain is associated with altered thalamic structure and function, which may disturb central processing and play a key role in the experience of neuropathic pain.
Ibrahim, Emad; Brackett, Nancy L; Lynne, Charles M
Couples with a spinal cord injured male partner require assisted ejaculation techniques to collect semen that can then be further used in various assisted reproductive technology methods to achieve a pregnancy. The majority of men sustaining a spinal cord injury regardless of the cause or the level of injury cannot ejaculate during sexual intercourse. Only a small minority can ejaculate by masturbation. Penile vibratory stimulation and electroejaculation are the two most common methods used to retrieve sperm. Other techniques such as prostatic massage and the adjunct application of other medications can be used, but the results are inconsistent. Surgical sperm retrieval should be considered as a last resort if all other methods fail. Special attention must be paid to patients with T6 and rostral levels of injury due to the risk of autonomic dysreflexia resulting from stimulation below the level of injury. Bladder preparation should be performed before stimulation if retrograde ejaculation is anticipated. Erectile dysfunction is ubiquitous in the spinal cord injured population but is usually easily managed and does not pose a barrier to semen retrieval in these men. Semen analysis parameters of men with spinal cord injury are unique for this population regardless of the method of retrieval, generally presenting as normal sperm concentration but abnormally low sperm motility and viability. When sperm retrieval is desired in this population, emphasis should be placed on initially trying the simple methods of penile vibratory stimulation or electroejaculation before resorting to more advanced and invasive surgical procedures. PMID:27048781
Gustin, S.M.; Wrigley, P.J.; Youssef, A.M.; McIndoe, L.; Wilcox, S.L.; Rae, C.D.; Edden, R; Siddall, P.J.; Henderson, L.A.
There is increasing evidence relating thalamic changes to the generation and/or maintenance of neuropathic pain. We have recently reported that neuropathic orofacial pain is associated with altered thalamic anatomy, biochemistry and activity, which may result in disturbed thalamocortical oscillatory circuits. Despite this evidence, it is possible that these thalamic changes are not responsible for the presence of pain per se, but result as a consequence of the injury. To clarify this subject, we compared brain activity and biochemistry in 12 people with below-level neuropathic pain after complete thoracic spinal cord injury to 11 people with similar injuries and no neuropathic pain and 21 age and gender matched healthy controls. Quantitative arterial spinal labelling was used to measure thalamic activity and magnetic resonance spectroscopy was used to determine changes in neuronal variability quantifying N-acetylaspartate and alterations in inhibitory function quantifying gamma amino butyric acid. This study revealed that the presence of neuropathic pain is associated with significant changes in thalamic biochemistry and neuronal activity. More specifically, the presence of neuropathic pain following spinal cord injury is associated with significant reductions in thalamic N-acetylaspartate, gamma amino butyric acid content and blood flow in the region of the thalamic reticular nucleus. Spinal cord injury on its own did not account for these changes. These findings support the hypothesis that neuropathic pain is associated with altered thalamic structure and function, which may disturb central processing and play a key role in the experience of neuropathic pain. PMID:24530612
Ibrahim, Emad; Brackett, Nancy L; Lynne, Charles M
Couples with a spinal cord injured male partner require assisted ejaculation techniques to collect semen that can then be further used in various assisted reproductive technology methods to achieve a pregnancy. The majority of men sustaining a spinal cord injury regardless of the cause or the level of injury cannot ejaculate during sexual intercourse. Only a small minority can ejaculate by masturbation. Penile vibratory stimulation and electroejaculation are the two most common methods used to retrieve sperm. Other techniques such as prostatic massage and the adjunct application of other medications can be used, but the results are inconsistent. Surgical sperm retrieval should be considered as a last resort if all other methods fail. Special attention must be paid to patients with T6 and rostral levels of injury due to the risk of autonomic dysreflexia resulting from stimulation below the level of injury. Bladder preparation should be performed before stimulation if retrograde ejaculation is anticipated. Erectile dysfunction is ubiquitous in the spinal cord injured population but is usually easily managed and does not pose a barrier to semen retrieval in these men. Semen analysis parameters of men with spinal cord injury are unique for this population regardless of the method of retrieval, generally presenting as normal sperm concentration but abnormally low sperm motility and viability. When sperm retrieval is desired in this population, emphasis should be placed on initially trying the simple methods of penile vibratory stimulation or electroejaculation before resorting to more advanced and invasive surgical procedures.
Ando, Takahiro; Sato, Shunichi; Kobayashi, Hiroaki; Nawashiro, Hiroshi; Ashida, Hiroshi; Hamblin, Michael R.; Obara, Minoru
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.
Liu, Jie; Yung, Andrew; Cripton, Peter; Kozlowski, Piotr; Tetzlaff, Wolfram; Oxland, Thomas
Abstract During traumatic spinal cord injury (SCI), the spinal cord is subject to external displacements that result in damage of neural tissues. These displacements produce complex internal deformations, or strains, of the spinal cord parenchyma. The aim of this study is to determine a relationship between these internal strains during SCI and primary damage to spinal cord gray matter (GM) in an in vivo rat contusion model. Using magnetic resonance imaging and novel image registration methods, we measured three-dimensional (3D) mechanical strain in in vivo rat cervical spinal cord (n = 12) during an imposed contusion injury. We then assessed expression of the neuronal transcription factor, neuronal nuclei (NeuN), in ventral horns of GM (at the epicenter of injury as well as at intervals cranially and caudally), immediately post-injury. We found that minimum principal strain was most strongly correlated with loss of NeuN stain across all animals (R2 = 0.19), but varied in strength between individual animals (R2 = 0.06–0.52). Craniocaudal distribution of anatomical damage was similar to measured strain distribution. A Monte Carlo simulation was used to assess strain field error, and minimum principal strain (which ranged from 8% to 36% in GM ventral horns) exhibited a standard deviation of 2.6% attributed to the simulated error. This study is the first to measure 3D deformation of the spinal cord and relate it to patterns of ensuing tissue damage in an in vivo model. It provides a platform on which to build future studies addressing the tolerance of spinal cord tissue to mechanical deformation. PMID:26729511
Bhatnagar, Tim; Liu, Jie; Yung, Andrew; Cripton, Peter; Kozlowski, Piotr; Tetzlaff, Wolfram; Oxland, Thomas
During traumatic spinal cord injury (SCI), the spinal cord is subject to external displacements that result in damage of neural tissues. These displacements produce complex internal deformations, or strains, of the spinal cord parenchyma. The aim of this study is to determine a relationship between these internal strains during SCI and primary damage to spinal cord gray matter (GM) in an in vivo rat contusion model. Using magnetic resonance imaging and novel image registration methods, we measured three-dimensional (3D) mechanical strain in in vivo rat cervical spinal cord (n = 12) during an imposed contusion injury. We then assessed expression of the neuronal transcription factor, neuronal nuclei (NeuN), in ventral horns of GM (at the epicenter of injury as well as at intervals cranially and caudally), immediately post-injury. We found that minimum principal strain was most strongly correlated with loss of NeuN stain across all animals (R(2) = 0.19), but varied in strength between individual animals (R(2) = 0.06-0.52). Craniocaudal distribution of anatomical damage was similar to measured strain distribution. A Monte Carlo simulation was used to assess strain field error, and minimum principal strain (which ranged from 8% to 36% in GM ventral horns) exhibited a standard deviation of 2.6% attributed to the simulated error. This study is the first to measure 3D deformation of the spinal cord and relate it to patterns of ensuing tissue damage in an in vivo model. It provides a platform on which to build future studies addressing the tolerance of spinal cord tissue to mechanical deformation.
Singh, Anoushka; Tetreault, Lindsay; Kalsi-Ryan, Suhkvinder; Nouri, Aria; Fehlings, Michael G
Background Spinal cord injury (SCI) is a traumatic event that impacts a patient’s physical, psychological, and social well-being and places substantial financial burden on health care systems. To determine the true impact of SCI, this systematic review aims to summarize literature reporting on either the incidence or prevalence of SCI. Methods A systematic search was conducted using PubMed, MEDLINE, MEDLINE in process, EMBASE, Cochrane Controlled Trial Register, and Cochrane Database of Systematic Reviews to identify relevant literature published through June 2013. We sought studies that provided regional, provincial/state, or national data on the incidence of SCI or reported estimates of disease prevalence. The level of evidence of each study was rated using a scale that evaluated study design, methodology, sampling bias, and precision of estimates. Results The initial search yielded 5,874 articles, 48 of which met the inclusion criteria. Forty-four studies estimated the incidence of SCI and nine reported the prevalence, with five discussing both. Of the incidence studies, 14 provided figures at a regional, ten at a state or provincial level and 21 at a national level. The prevalence of SCI was highest in the United States of America (906 per million) and lowest in the Rhone-Alpes region, France (250 per million) and Helsinki, Finland (280 per million). With respect to states and provinces in North America, the crude annual incidence of SCI was highest in Alaska (83 per million) and Mississippi (77 per million) and lowest in Alabama (29.4 per million), despite a large percentage of violence injuries (21.2%). Annual incidences were above 50 per million in the Hualien County in Taiwan (56.1 per million), the central Portugal region (58 per million), and Olmsted County in Minnesota (54.8 per million) and were lower than 20 per million in Taipei, Taiwan (14.6 per million), the Rhone-Alpes region in France (12.7 per million), Aragon, Spain (12.1 per million
Smith, Hannah K; Durnford, Andrew J; Sherlala, Khaled; Merriam, William F
A 37-year-old man, amateur rugby player sustained a hyperextension injury to his lower thoracic spine during a scrum collapse. The patient developed extreme hyperpathia in the T10-12 dermatome, and parasthesia from T12 to S1 in the left lower limb. Medical Research Council grade 5 power was regained rapidly within minutes of the accident, and the hyperpathia resolved within a week. MRI showed contusion of the spinal cord at T10 level but no associated osseoligamentous injury. Six months later, parasthesia and subjective weakness remained in the left lower limb. To our knowledge, this is the first description of a lower thoracic spinal cord injury without radiographic abnormality following an isolated low-energy injury in a skeletally mature patient.
Kirshblum, S. C.; Biering-Sorensen, F.; Betz, R.; Burns, S.; Donovan, W.; Graves, D. E.; Johansen, M.; Jones, L.; Mulcahey, M. J.; Rodriguez, G. M.; Schmidt-Read, M.; Steeves, J. D.; Tansey, K.; Waring, W.
The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is routinely used to determine the levels of injury and to classify the severity of the injury. Questions are often posed to the International Standards Committee of the American Spinal Injury Association regarding the classification. The committee felt that disseminating some of the challenging questions posed, as well as the responses, would be of benefit for professionals utilizing the ISNCSCI. Case scenarios that were submitted to the committee are presented with the responses as well as the thought processes considered by the committee members. The importance of this documentation is to clarify some points as well as update the SCI community regarding possible revisions that will be needed in the future based upon some rules that require clarification. PMID:24559416
Biering-Sørensen, F.; Betz, R.; Burns, S.; Donovan, W.; Graves, D.E.; Johansen, M.; Jones, L.; Mulcahey, M.J.; Rodriguez, G.M.; Schmidt-Read, M.; Steeves, J.D.; Tansey, K.; Waring, W.
The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is routinely used to determine levels of injury and to classify the severity of the injury. Questions are often posed to the International Standards Committee of the American Spinal Injury Association (ASIA) regarding the classification. The committee felt that disseminating some of the challenging questions posed, as well as the responses, would be of benefit for professionals utilizing the ISNCSCI. Case scenarios that were submitted to the committee are presented with the responses as well as the thought processes considered by the committee members. The importance of this documentation is to clarify some points as well as update the SCI community regarding possible revisions that will be needed in the future based upon some rules that require clarification. PMID:25477729
Kirshblum, S C; Biering-Sorensen, F; Betz, R; Burns, S; Donovan, W; Graves, D E; Johansen, M; Jones, L; Mulcahey, M J; Rodriguez, G M; Schmidt-Read, M; Steeves, J D; Tansey, K; Waring, W
The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is routinely used to determine the levels of injury and to classify the severity of the injury. Questions are often posed to the International Standards Committee of the American Spinal Injury Association regarding the classification. The committee felt that disseminating some of the challenging questions posed, as well as the responses, would be of benefit for professionals utilizing the ISNCSCI. Case scenarios that were submitted to the committee are presented with the responses as well as the thought processes considered by the committee members. The importance of this documentation is to clarify some points as well as update the SCI community regarding possible revisions that will be needed in the future based upon some rules that require clarification.
Introduction Spinal cord injury is a cause of severe disability and mortality. The pharmacological and non-pharmacological methods used, are unable to improve the quality of life in spinal cord injury. Spinal disorders have been treated with human embryonic stem cells. Magnetic resonance imaging and tractography were used as imaging modality to document the changes in the damaged cord, but the magnetic resonance imaging tractography was seen to be more sensitive in detecting the changes in the spinal cord. The present study was conducted to evaluate the diagnostic modality of magnetic resonance imaging tractography to determine the efficacy of human embryonic stem cells in chronic spinal cord injury. Materials and methods The study included the patients with spinal cord injury for whom magnetic resonance imaging tractography was performed before and after the therapy. Omniscan (gadodiamide) magnetic resonance imaging tractography was analyzed to assess the spinal defects and the improvement by human embryonic stem cell treatment. The patients were also scored by American Spinal Injury Association scale. Results Overall, 15 patients aged 15-44 years with clinical manifestations of spinal cord injury had magnetic resonance imaging tractography performed. The average treatment period was nine months. The majority of subjects ( n = 13) had American Spinal Injury Association score A, and two patients were at score C at the beginning of therapy. At the end of therapy, 10 patients were at score A, two patients were at score B and three patients were at score C. Improvements in patients were clearly understood through magnetic resonance imaging tractography as well as in clinical signs and symptoms. Conclusion Magnetic resonance imaging tractography can be a crucial diagnostic modality to assess the improvement in spinal cord injury patients.
Bonner, Joseph F; Steward, Oswald
Spinal cord injury (SCI) disrupts the long axonal tracts of the spinal cord leading to devastating loss of function. Cell transplantation in the injured spinal cord has the potential to lead to recovery after SCI via a variety of mechanisms. One such strategy is the formation of neuronal relays between injured long tract axons and denervated neurons. The idea of creating a neuronal relay was first proposed over 25 years ago when fetal tissue was first successfully transplanted into the injured rodent spinal cord. Advances in labeling of grafted cells and the development of neural stem cell culturing techniques have improved the ability to create and refine such relays. Several recent studies have examined the ability to create a novel neuronal circuit between injured axons and denervated targets. This approach is an alternative to long-distance regeneration of damaged axons that may provide a meaningful degree of recovery without direct recreation of lost pathways. This brief review will examine the contribution of fetal grafting to current advances in neuronal grafting. Of particular interest will be the ability of transplanted neurons derived from fetal grafts, neural precursor cells and neural stem cells to reconnect long distance motor and sensory pathways of the injured spinal cord. This article is part of a Special Issue entitled SI: Spinal cord injury.
Martin, John H.
As most spinal cord injuries (SCIs) are incomplete, an important target for promoting neural repair and recovery of lost motor function is to promote the connections of spared descending spinal pathways with spinal motor circuits. Among the pathways, the corticospinal tract (CST) is most associated with skilled voluntary functions in humans and many animals. CST loss, whether at its origin in the motor cortex or in the white matter tracts subcortically and in the spinal cord, leads to movement impairments and paralysis. To restore motor function after injury will require repair of the damaged CST. In this review, I discuss how knowledge of activity-dependent development of the CST—which establishes connectional specificity through axon pruning, axon outgrowth, and synaptic competition among CST terminals—informed a novel activity-based therapy for promoting sprouting of spared CST axons after injur in mature animals. This therapy, which comprises motor cortex electrical stimulation with and without concurrent trans-spinal direct current stimulation, leads to an increase in the gray matter axon length of spared CST axons in the rat spinal cord and, after a pyramidal tract lesion, restoration of skilled locomotor movements. I discuss how this approach is now being applied to a C4 contusion rat model. PMID:27857728
Gong, Gu; Yuan, Li-bang; Hu, Ling; Wu, Wei; Yin, Liang; Hou, Jing-li; Liu, Ying-hai; Zhou, Le-shun
Aim: To investigate the neuroprotective effect of glycyrrhizin (Gly) against the ischemic injury of rat spinal cord and the possible role of the nuclear protein high-mobility group box 1 (HMGB1) in the process. Methods: Male Sprague-Dawley rats were subjected to 45 min aortic occlusion to induce transient lumbar spinal cord ischemia. The motor functions of the animals were assessed according to the modified Tarlov scale. The animals were sacrificed 72 h after reperfusion and the lumbar spinal cord segment (L2–L4) was taken out for histopathological examination and Western blotting analysis. Serum inflammatory cytokine and HMGB1 levels were analyzed using ELISA. Results: Gly (6 mg/kg) administered intravenously 30 min before inducing the transient lumbar spinal cord ischemia significantly improved the hind-limb motor function scores, and reduced the number of apoptotic neurons, which was accompanied by reduced levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the plasma and injured spinal cord. Moreover, the serum HMGB1 level correlated well with the serum TNF-α, IL-1β and IL-6 levels during the time period of reperfusion. Conclusion: The results suggest that Gly can attenuate the transient spinal cord ischemic injury in rats via reducing inflammatory cytokines and inhibiting the release of HMGB1. PMID:22158106
fractures , and recent reports within the field of spine surgery as a whole. CONCLUSIONS: American and coalition forces are sustaining the highest...the Egyptians de- vised means to attempt reduction of fractures and disloca- tions . Until the age of gunpowder, however, most spine injuries...herniation or epi- dural hematoma . The guideline also declares that treat- ment with high-dose methylprednisolone per the National Acute Spinal Cord Injury
Crupi, Rosalia; Impellizzeri, Daniela; Bruschetta, Giuseppe; Cordaro, Marika; Paterniti, Irene; Siracusa, Rosalba; Cuzzocrea, Salvatore; Esposito, Emanuela
Spinal cord injury (SCI) stimulates activation of astrocytes and infiltration of immune cells at the lesion site; however, the mechanism that promotes the birth of new neurons is still under debate. Neuronal regeneration is restricted after spinal cord injury, but can be stimulated by experimental intervention. Previously we demonstrated that treatment co-ultramicronized palmitoylethanolamide and luteolin, namely co-ultraPEALut, reduced inflammation. The present study was designed to explore the neuroregenerative properties of co-ultraPEALut in an estabished murine model of SCI. A vascular clip was applied to the spinal cord dura at T5–T8 to provoke injury. Mice were treated with co-ultraPEALut (1 mg/kg, intraperitoneally) daily for 72 h after SCI. Co-ultraPEALut increased the numbers of both bromodeoxyuridine-positive nuclei and doublecortin-immunoreactive cells in the spinal cord of injured mice. To correlate neuronal development with synaptic plasticity a Golgi method was employed to analyze dendritic spine density. Co-ultraPEALut administration stimulated expression of the neurotrophic factors brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, nerve growth factor, and neurotrophin-3. These findings show a prominent effect of co-ultraPEALut administration in the management of survival and differentiation of new neurons and spine maturation, and may represent a therapeutic treatment for spinal cord and other traumatic diseases. PMID:27014061
Liu, Zhi-Qiang; Zhang, Hong-Bin; Wang, Jian; Xia, Li-Jian; Zhang, Wei
Ischemia/reperfusion (I/R) induced spinal cord injury is an important pathologic mechanism leading to the paraplegia observed after surgery to repairaortic aneurysms. This study aims to investigate the neuroprotective effects of Lipoxin A4 and its potential mechanism in a rabbit model with I/R spinal cord injury. Forty-five rabbits were randomly divided into three groups: sham group, I/R group and Lipoxin A4 group. Rabbits were subject to 30 min aortic occlusion to induce transient spinal cord ischemia. All animals were sacrificed after neurological evaluation with modified Tarlov criteria at the 48th hour after reperfusion, and the spinal cord segments (L4-6) were harvested for histopathological examination, as well as local malondialdehyde (MDA) and total superoxide dismutase (SOD) activity analysis. All animals in the I/R group became paraplegic. While after 48-hour treatment, compared with I/R group, Lipoxin A4 significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05). These results suggest that Lipoxin A4 can ameliorate I/R induced spinal cord injury in Rabbit through its antiapoptosis and antioxidant activity. PMID:26550197
Zhang, Rui-ping; Xu, Cheng; Liu, Yin; Li, Jian-ding; Xie, Jun
An important factor in improving functional recovery from spinal cord injury using stem cells is maximizing the number of transplanted cells at the lesion site. Here, we established a contusion model of spinal cord injury by dropping a weight onto the spinal cord at T7-8. Superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells were transplanted into the injured spinal cord via the subarachnoid space. An outer magnetic field was used to successfully guide the labeled cells to the lesion site. Prussian blue staining showed that more bone marrow mesenchymal stem cells reached the lesion site in these rats than in those without magnetic guidance or superparamagnetic iron oxide labeling, and immunofluorescence revealed a greater number of complete axons at the lesion site. Moreover, the Basso, Beattie and Bresnahan (BBB) locomotor rating scale scores were the highest in rats with superparamagnetic labeling and magnetic guidance. Our data confirm that superparamagnetic iron oxide nanoparticles effectively label bone marrow mesenchymal stem cells and impart sufficient magnetism to respond to the external magnetic field guides. More importantly, superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells can be dynamically and non-invasively tracked in vivo using magnetic resonance imaging. Superparamagnetic iron oxide labeling of bone marrow mesenchymal stem cells coupled with magnetic guidance offers a promising avenue for the clinical treatment of spinal cord injury. PMID:25878588
Mountney, Andrea; Zahner, Matthew R; Sturgill, Elizabeth R; Riley, Christopher J; Aston, Jeffrey W; Oudega, Martin; Schramm, Lawrence P; Hurtado, Andres; Schnaar, Ronald L
Axon regeneration in the central nervous system is severely hampered, limiting functional recovery. This is in part because of endogenous axon regeneration inhibitors that accumulate at the injury site. Therapeutic targeting of these inhibitors and their receptors may facilitate axon outgrowth and enhance recovery. A rat model of spinal cord contusion injury was used to test the effects of two bacterial enzyme therapies that target independent axon regeneration inhibitors, sialidase (Vibrio cholerae) and chondroitinase ABC (ChABC, Proteus vulgaris). The two enzymes, individually and in combination, were infused for 2 weeks via implanted osmotic pumps to the site of a moderate thoracic spinal cord contusion injury. Sialidase was completely stable, whereas ChABC retained>30% of its activity in vivo over the 2 week infusion period. Immunohistochemistry revealed that infused sialidase acted robustly throughout the spinal cord gray and white matter, whereas ChABC activity was more intense superficially. Sialidase treatment alone resulted in improved behavioral and anatomical outcomes. Rats treated exclusively with sialidase showed significantly increased hindlimb motor function, evidenced by higher Basso Beattie and Bresnahan (BBB) and BBB subscores, and fewer stepping errors on a horizontal ladder. Sialidase-treated rats also had increased serotonergic axons caudal to the injury. ChABC treatment, in contrast, did not enhance functional recovery or alter axon numbers after moderate spinal cord contusion injury, and dampened the response of sialidase in the dual enzyme treatment group. We conclude that sialidase infusion enhanced recovery from spinal cord contusion injury, and that combining sialidase with ChABC failed to improve outcomes.
Epstein, Nancy E.; Hollingsworth, Renee
Background: The classical clinical presentation, neuroradiographic features, and conservative vs. surgical management of traumatic cervical central spinal cord (CSS) injury remain controversial. Methods: CSS injuries, occurring in approximately 9.2% of all cord injuries, are usually attributed to significant hyperextension trauma combined with congenital/acquired cervical stenosis/spondylosis. Patients typically present with greater motor deficits in the upper vs. lower extremities accompanied by patchy sensory loss. T2-weighted magnetic resonance (MR) scans usually show hyperintense T2 intramedullary signals reflecting acute edema along with ligamentous injury, while noncontrast computed tomography (CT) studies typically show no attendant bony pathology (e.g. no fracture, dislocation). Results: CSS constitute only a small percentage of all traumatic spinal cord injuries. Aarabi et al. found CSS patients averaged 58.3 years of age, 83% were male and 52.4% involved accidents/falls in patients with narrowed spinal canals (average 5.6 mm); their average American Spinal Injury Association (ASIA) motor score was 63.8, and most pathology was at the C3-C4 and C4-C5 levels (71%). Surgery was performed within 24 h (9 patients), 24–48 h (10 patients), or after 48 h (23 patients). In the Brodell et al. study of 16,134 patients with CSS, 39.7% had surgery. In the Gu et al. series, those with CSS and stenosis/ossification of the posterior longitudinal ligament (OPLL) exhibited better outcomes following laminoplasty. Conclusions: Recognizing the unique features of CSS is critical, as the clinical, neuroradiological, and management strategies (e.g. conservative vs. surgical management: early vs. late) differ from those utilized for other spinal cord trauma. Increased T2-weighted MR images best document CSS, while CT studies confirm the absence of fracture/dislocation. PMID:26005576
Zhou, Kailiang; Sansur, Charles A.; Xu, Huazi; Jia, Xiaofeng
Previous studies have indicated that autophagy plays a critical role in spinal cord injury (SCI), including traumatic spinal cord injury (TSCI) and ischemia-reperfusion spinal cord injury (IRSCI). However, while the understanding of mechanisms underlying autophagy in SCI has progressed, there remain several controversial points: (1) temporal pattern results of autophagic activation after SCI are not consistent across studies; (2) effect of accumulation of autophagosomes due to the blockade or enhancement of autophagic flux is uncertain; (3) overall effect of enhanced autophagy remains undefined, with both beneficial and detrimental outcomes reported in SCI literature. In this review, the temporal pattern of autophagic activation, autophagic flux, autophagic cell death, relationship between autophagy and apoptosis, and pharmacological intervention of autophagy in TSCI (contusion injury, compression injury and hemisection injury) and IRSCI are discussed. Types of SCI and severity appear to contribute to differences in outcomes regarding temporal pattern, flux, and function of autophagy. With future development of specific strategies on autophagy intervention, autophagy may play an important role in improving functional recovery in patients with SCI. PMID:28230791
Acosta, A M; Kirsch, R F; van der Helm, F C
The shoulder kinematics of five able-bodied subjects and those of five arms in three subjects with spinal cord injuries at C5 or C6 levels were measured as the subjects elevated their arms in three different planes: coronal, scapular and sagittal. The range of humeral elevation was significantly reduced in all spinal cord injury (SCI) subjects relative to able-bodied subjects. Over this restricted range of humeral motion, the scapula of SCI subjects tended to be medially rotated, relative to able-bodied subjects, and the protraction and spinal tilt angles of the scapula of the SCI subjects indicated scapular winging. These results are consistent with paralysis or at least with significant weakness of the serratus anterior muscle. If further study confirms this hypothesis, functional neuromuscular stimulation of the serratus anterior muscle via a nerve cuff electrode may be an effective intervention for improving shoulder function in C5-C6 SCI.
Duan, Hongmei; Ge, Weihong; Zhang, Aifeng; Xi, Yue; Chen, Zhihua; Luo, Dandan; Cheng, Yin; Fan, Kevin S.; Horvath, Steve; Sofroniew, Michael V.; Cheng, Liming; Yang, Zhaoyang; Sun, Yi E.; Li, Xiaoguang
Spinal cord injury (SCI) is considered incurable because axonal regeneration in the central nervous system (CNS) is extremely challenging, due to harsh CNS injury environment and weak intrinsic regeneration capability of CNS neurons. We discovered that neurotrophin-3 (NT3)-loaded chitosan provided an excellent microenvironment to facilitate nerve growth, new neurogenesis, and functional recovery of completely transected spinal cord in rats. To acquire mechanistic insight, we conducted a series of comprehensive transcriptome analyses of spinal cord segments at the lesion site, as well as regions immediately rostral and caudal to the lesion, over a period of 90 days after SCI. Using weighted gene coexpression network analysis (WGCNA), we established gene modules/programs corresponding to various pathological events at different times after SCI. These objective measures of gene module expression also revealed that enhanced new neurogenesis and angiogenesis, and reduced inflammatory responses were keys to conferring the effect of NT3-chitosan on regeneration. PMID:26460053
Yang, Zhaoyang; Zhang, Aifeng; Duan, Hongmei; Zhang, Sa; Hao, Peng; Ye, Keqiang; Sun, Yi E.; Li, Xiaoguang
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
Nagai, Jun; Kitamura, Yoshiteru; Owada, Kazuki; Yamashita, Naoya; Takei, Kohtaro; Goshima, Yoshio; Ohshima, Toshio
Axonal outgrowth inhibitors and scar formation are two major obstacles to central nervous system (CNS) repair. No target molecule that regulates both axonal growth and scarring has been identified. Here we identified collapsin response mediator protein 4 (CRMP4), a common mediator of inhibitory signals after neural injury, as a crucial factor that contributes to both axonal growth inhibition and scarring after spinal cord injury (SCI). We found increases in the inhibitory and toxic forms of CRMP4 in injured spinal cord. Notably, CRMP4 expression was evident in inflammatory cells as well as in neurons after spinal cord transection. Crmp4−/− mice displayed neuroprotection against SCI and reductions in inflammatory response and scar formation. This permissive environment for axonal growth due to CRMP4 deletion restored locomotor activity at an unusually early phase of healing. These results suggest that deletion of CRMP4 is a unique therapeutic strategy that overcomes two obstacles to CNS repair after SCI. PMID:25652774
Duan, Hongmei; Ge, Weihong; Zhang, Aifeng; Xi, Yue; Chen, Zhihua; Luo, Dandan; Cheng, Yin; Fan, Kevin S; Horvath, Steve; Sofroniew, Michael V; Cheng, Liming; Yang, Zhaoyang; Sun, Yi E; Li, Xiaoguang
Spinal cord injury (SCI) is considered incurable because axonal regeneration in the central nervous system (CNS) is extremely challenging, due to harsh CNS injury environment and weak intrinsic regeneration capability of CNS neurons. We discovered that neurotrophin-3 (NT3)-loaded chitosan provided an excellent microenvironment to facilitate nerve growth, new neurogenesis, and functional recovery of completely transected spinal cord in rats. To acquire mechanistic insight, we conducted a series of comprehensive transcriptome analyses of spinal cord segments at the lesion site, as well as regions immediately rostral and caudal to the lesion, over a period of 90 days after SCI. Using weighted gene coexpression network analysis (WGCNA), we established gene modules/programs corresponding to various pathological events at different times after SCI. These objective measures of gene module expression also revealed that enhanced new neurogenesis and angiogenesis, and reduced inflammatory responses were keys to conferring the effect of NT3-chitosan on regeneration.
Crowell, Andrew D.; King, Kevin; Deitermann, Annika; Miranpuri, Gurwattan S.; Resnick, Daniel K.
Neuropathic pain (NP) is common among spinal cord injury (SCI) patients, and there remain clinical difficulties in treating NP due to the lack of understanding of underlying mechanisms. Extracellular proteins, such as matrix metalloproteinase and β-catenin, have been shown to be activated in the spinal cord regions following an injury, and may play a key role in contributing to NP states. While these extracellular proteins have been used as therapeutic targets in the spinal cord, there has also been evidence of up-regulation in the hypothalamus following a SCI. We hypothesize that the hypothalamus is involved in regulating NP following a SCI, and hence should be researched further to determine if it is a viable target for future therapeutic treatments. PMID:27721586
Shuai, Lang; Yu, Guo-hua; Feng, Zhen; Wang, Wan-song; Sun, Wei-ming; Zhou, Lu; Yan, Yin
Paraplegic gait orthosis has been shown to help paraplegic patients stand and walk, although this method cannot be individualized for patients with different spinal cord injuries and functional recovery of the lower extremities. There is, however, a great need to develop individualized paraplegic orthosis to improve overall quality of life for paraplegic patients. In the present study, 36 spinal cord (below T4) injury patients were equally and randomly divided into control and observation groups. The control group received systematic rehabilitation training, including maintenance of joint range of motion, residual muscle strength training, standing training, balance training, and functional electrical stimulation. The observation group received an individualized paraplegic locomotion brace and functional training according to the various spinal cord injury levels and muscle strength based on comprehensive systematic rehabilitation training. After 3 months of rehabilitation training, the observation group achieved therapeutic locomotion in 8 cases, family-based locomotion in 7 cases, and community-based locomotion in 3 cases. However, locomotion was not achieved in any of the control group patients. These findings suggest that individualized paraplegic braces significantly improve activity of daily living and locomotion in patients with thoracolumbar spinal cord injury. PMID:28197198
Jones, Michael L.; Marini, Irmo; Slate, John R.
Pressure ulcers are common among people with spinal cord injury (SCI) and not only are costly to treat but also affect the quality of life of those affected by them. Despite a plethora of literature on prevention, there are few wellness studies focusing on the practices of people who do not develop pressure ulcers. This preliminary study sought to…
Stogov, M V; Shchurova, E N; Bliudenov, D N
A comparative analysis of biochemical parameters of blood serum and daily urine in patients with urolithiasis developed after spinal cord injury (study group--35 patients) and patients without development of the disease (comparison group--20 patients) was performed. It was found that patients after spinal cord injury have developed productive azotemia, which led to the disruption of renal excretory function (accumulation of urea and creatinine in blood, and lowering their clearance). Against this background, there is violation of excretion of uric acid, magnesium, decreased sensitivity of the renal tubules to aldosterone (in patients with nephrolithiasis K/Na ratio in urine was lower). As a result, patients have decreased reabsorption of sodium and water retention, increased urine osmolality; against the background of electrolyte imbalance in urine, this leads to the formation of stones. In patients with spinal cord injuries, main trigger mechanism of formation of urinary stones was excessive posttraumatic azotemia. The high concentration of the products of protein-nitrogen catabolism in the serum of patients in the acute and early periods of spinal cord injury may be unfavorable criterion determining the significant risk of developing of kidney stones.
Diaz Quiroz, Juan Felipe; Li, Yuping; Aparicio, Conrado; Echeverri, Karen
Spinal cord injury affects millions of people around the world, however, limited therapies are available to improve the quality of life of these patients. Spinal cord injury is usually modeled in rats and mice using contusion or complete transection models and this has led to a deeper understanding of the molecular and cellular complexities of the injury. However, it has not to date led to development of successful novel therapies, this is in part due to the complexity of the injury and the difficulty of deciphering the exact roles and interactions of different cells within this complex environment. Here we developed a collagen matrix that can be molded into the 3D tubular shape with a lumen and can hence support cell interactions in a similar architecture to a spinal cord. We show that astrocytes can be successfully grown on this matrix in vitro and when injured, the cells respond as they do in vivo and undergo reactive gliosis, one of the steps that lead to formation of a glial scar, the main barrier to spinal cord regeneration. In the future, this system can be used to quickly assess the effect of drugs on glial scar protein activity or to perform live imaging of labeled cells after exposure to drugs.
Deswysen, Yannick; Labeau, Jason; Kaminski, Ludovik; Astarci, Parla
We report the cases of two patients who presented with screw misplacement following spinal surgery. Both benefited from unusual vascular surgical management with removal of the material and injection of biological glue facing the injury, with uneventful postoperative courses. PMID:28097186
Recovery Scale for Spinal Cord Injury: Inpatient and Outpatient Rehabilitation PRINCIPAL INVESTIGATOR: Craig Velozo, PhD, OTR ...AUTHOR(S) 5d. PROJECT NUMBER Craig Velozo, Ph.D., PT Andrea L. Behrman, Ph.D., OTR 5e. TASK NUMBER D. Michele Basso, Ed.D., PT E-Mail
Sadowsky, Cristina L.; McDonald, John W.
Physical rehabilitation following spinal cord injury-related paralysis has traditionally focused on teaching compensatory techniques, thus enabling the individual to achieve day-to-day function despite significant neurological deficits. But the concept of an irreparable central nervous system (CNS) is slowly being replaced with evidence related to…
Ando, Takahiro; Kobayashi, Hiroaki; Nawashiro, Hiroshi; Ashida, Hiroshi; Hamblin, Michael R.; Obara, Minoru
Abstract. The effects of laser polarization on the efficacy of near-infrared low-level laser therapy for spinal cord injury (SCI) are presented. Rat spinal cords were injured with a weight-drop device, and the lesion sites were directly irradiated with a linearly polarized 808-nm diode laser positioned either perpendicular or parallel to the spine immediately after the injury and daily for five consecutive days. Functional recovery was assessed daily by an open-field test. Regardless of the polarization direction, functional scores of SCI rats that were treated with the 808-nm laser irradiation were significantly higher than those of SCI alone group (Group 1) from day 5 after injury. The locomotive function of SCI rats irradiated parallel to the spinal column (Group 3) was significantly improved from day 10 after injury, compared to SCI rats treated with the linear polarization perpendicular to the spinal column (Group 2). There were no significant differences in ATP contents in the injured tissue among the three groups. We speculate that the higher efficacy with parallel irradiation is attributable to the deeper light penetration into tissue with anisotropic scattering. PMID:24030687
dependent male infertility is characterized by a significant reduction in numbers and quality of functional sperm. The mechanism(s) underlying this...term effects on the blood-testis-barrier as a mechanism underlying male infertility following spinal cord injury. Goals/Milestones (Example) CY12/13
Diaz Quiroz, Juan Felipe; Li, Yuping; Aparicio, Conrado; Echeverri, Karen
Spinal cord injury affects millions of people around the world, however, limited therapies are available to improve the quality of life of these patients. Spinal cord injury is usually modeled in rats and mice using contusion or complete transection models and this has led to a deeper understanding of the molecular and cellular complexities of the injury. However, it has not to date led to development of successful novel therapies, this is in part due to the complexity of the injury and the difficulty of deciphering the exact roles and interactions of different cells within this complex environment. Here we developed a collagen matrix that can be molded into the 3D tubular shape with a lumen and can hence support cell interactions in a similar architecture to a spinal cord. We show that astrocytes can be successfully grown on this matrix in vitro and when injured, the cells respond as they do in vivo and undergo reactive gliosis, one of the steps that lead to formation of a glial scar, the main barrier to spinal cord regeneration. In the future, this system can be used to quickly assess the effect of drugs on glial scar protein activity or to perform live imaging of labeled cells after exposure to drugs. PMID:28123426
Saxena, Tarun; Deng, Bin; Stelzner, Dennis; Hasenwinkel, Julie; Chaiken, Joseph
Raman spectroscopy was used to study temporal molecular changes associated with spinal cord injury (SCI) in a rat model. Raman spectra of saline-perfused, injured, and healthy rat spinal cords were obtained and compared. Two injury models, a lateral hemisection and a moderate contusion were investigated. The net fluorescence and the Raman spectra showed clear differences between the injured and healthy spinal cords. Based on extensive histological and biochemical characterization of SCI available in the literature, these differences were hypothesized to be due to cell death, demyelination, and changes in the extracellular matrix composition, such as increased expression of proteoglycans and hyaluronic acid, at the site of injury where the glial scar forms. Further, analysis of difference spectra indicated the presence of carbonyl containing compounds, hypothesized to be products of lipid peroxidation and acid catalyzed hydrolysis of glycosaminoglycan moieties. These results compared well with in vitro experiments conducted on chondroitin sulfate sugars. Since the glial scar is thought to be a potent biochemical barrier to nerve regeneration, this observation suggests the possibility of using near infrared Raman spectroscopy to study injury progression and explore potential treatments ex vivo, and ultimately monitor potential remedial treatments within the spinal cord in vivo.
Kullmann, Lajos; Toth, Katalin
The aim of the study is to investigate the applicability of structured interviews for exploration of quality-of-life goals using an established instrument. Structured interviews were performed using WHOQOL-BREF and Disabilities Module as guideline with 35 clients admitted for first rehabilitation intervention after spinal cord injury. Although…
Giner-Pascual, Manuel; Alcanyis-Alberola, Modesto; Millan Gonzalez, Luis; Aguilar-Rodriguez, Marta; Querol, Felipe
The objective of this study was to determine the relationship between shoulder pain and the position of the seat of a wheelchair relative to the ground and to determine the relationship between shoulder pain and structural damage. A transversal study of a patient cohort of 140 patients with grade A and B spinal cord injuries below the T1 vertebra,…
Cobo-Cuenca, Ana Isabel; Martín-Espinosa, Noelia M; Píriz Campos, Rosa M
The impact of spinal cord injury and its sequels requires important efforts of adaptation. In several studies, people with spinal cord injury claim to have covered most of their needs at physical, emotional and social level, but they are not yet fully satisfied with their sexual life. Sexual function is usually impaired in men with spinal cord injuries, and is sometimes related to problems of erection, ejaculation and/or orgasm. This issue is not a priority in the first phase, but it appears over the subsequent periods when patients often ask for a solution to this problem. A case-study is presented of a 25 year old male with chronic complete spinal cord injury (ASIA A), L4-L5 level, who reported sexual dysfunction and attended an annual review in the National Hospital for Paraplegics. After performing a nursing assessment using the functional health patterns of Gordon, the team proposed a nursing care plan according to the taxonomy of NANDA (North American Nursing Association), NOC (Nursing Outcome Classification) and NIC (Nursing Intervention Classification). Nurses are the healthcare professionals who have more direct and continuous contact with these patients. Specific programs need to be designed to provide them with the sexual education, which should contain adequate emotional and sexual information. We believe that an appropriate and systematic assessment of patient's sexuality, as well as the application of the (NANDA, NOC, NIC) nurse methodology, may be very helpful in improving the outcomes of these specific interventions.
Collyer, E; Catenaccio, A; Lemaitre, D; Diaz, P; Valenzuela, V; Bronfman, F; Court, F A
After an incomplete spinal cord injury (SCI), partial recovery of locomotion is accomplished with time. Previous studies have established a functional link between extension of axon collaterals from spared spinal tracts and locomotor recovery after SCI, but the tissular signals triggering collateral sprouting have not been identified. Here, we investigated whether axonal degeneration after SCI contributes to the sprouting of collaterals from axons spared after injury. To this end, we evaluated collateral sprouting from BDA-labeled uninjured corticospinal axons after spinal cord hemisection (SCI(H)) in wild type (WT) mouse and Wld(S) mouse strains, which shows a significant delay in Wallerian degeneration after injury. After SCI(H), spared fibers of WT mice extend collateral sprouts to both intact and denervated sides of the spinal cord distant from the injury site. On the contrary, in the Wld(S) mice collateral sprouting from spared fibers was greatly reduced after SCI(H). Consistent with a role for collateral sprouting in functional recovery after SCI, locomotor recovery after SCI(H) was impaired in Wld(S) mice compared to WT animals. In conclusion, our results identify axonal degeneration as one of the triggers for collateral sprouting from the contralesional uninjured fibers after an SCI(H). These results open the path for identifying molecular signals associated with tissular changes after SCI that promotes collateral sprouting and functional recovery.
Quinzaños-Fresnedo, J; Rodríguez-Reyes, G; Mendoza-Cosío, C; Pérez-Zavala, R; Márquez-Guitérrez, E A; Hernández-Sandoval, S
Study design: Case report. Objectives: To highlight the importance of the integral multidisciplinary management of a patient with complete chronic spinal cord injury and hip disarticulation secondary to pressure ulcers (PU). Setting: Mexico City. Methods: The case of a 40-year-old male violinist with a spinal cord injury, American Spinal Injury Association Impairment Scale A and neurological level T4, is reported. The patient initiated with bilateral ischiatic, left trochanteric and sacral PU. The ulcers were complicated with infection with sluggish evolution. Thus, it was decided a multidisciplinary management by means of left hip disarticulation and elaboration of a cosmetic prosthesis and the manufacture of a viscous elastic foam cushion for the prevention of new PU. The patient was quickly included in his professional and social activities. Conclusion: This study proves that multidisciplinary management of patients with spinal cord injury with complications such as the presence of PU that are resistant to noninvasive treatment can be the solution for the patient’s reintegration into their normal life with adequate quality of life. PMID:28053719
Wang, Ping; Low, K. H.; McGregor, Alison H.; Tow, Adela
In order to identify optimal rehabilitation strategies for spinal cord injury (SCI) participants, assessment of impaired walking is required to detect, monitor and quantify movement disorders. In the proposed assessment, ten healthy and seven SCI participants were recruited to perform an over-ground walking test at slow walking speeds. SCI…
Frank, Robert G.; And Others
Identified and validated two subgroups in group of 53 persons with spinal cord injury by applying cluster-analytic procedures to subjects' self-reported coping and health locus of control belief scores. Cluster 1 coped less effectively and tended to be psychologically distressed; Cluster 2 subjects emphasized internal health attributions and…
journal.pone.0096408 Editor: Hatem E. Sabaawy, Rutgers- Robert wood Johnson Medical School, United States of America Received January 23, 2014; Accepted April 7...functional recovery after spinal cord injury. Journal of neurochemistry 121: 818–829. 8. Stirling DP, Yong VW (2008) Dynamics of the inflammatory response
Skinner, Amy L.; Armstrong, Kevin J.; Rich, John
Studies of depression in individuals with spinal cord injuries (SCI) over a 15-year period were examined to determine if researchers used consistent diagnostic measures. The Beck Depression Inventory was the most frequently used instrument, but there was inconsistency among methods employed and disagreement regarding the inclusion of somatic…
Cardoso, Fernando Luiz; Savall, Ana Carolina R.; Mendes, Aline K.
The aim of this study was to assess the impact of spinal cord injury on men's sexual motivation, through the sexual desire self-assessment, and the sexual arousal and orgasm physiological responses. This research consisted of a descriptive, nonprobabilistic and comparative study, designed to outline the target population characteristics to compare…
Arango-Lasprilla, Juan Carlos; Cardoso, Elizabeth da Silva; Wilson, Lisa M.; Romero, Maria G.; Chan, Fong; Sung, Connie
Purpose: This study examined demographic and rehabilitation service variables affecting employment outcomes of people with spinal cord injury (SCI) receiving services from state vocational rehabilitation agencies. A secondary purpose was to determine whether there are disparities in services and outcomes between European American and Hispanic…
Krause, James S.; Reed, Karla S.
The authors identify the association of educational milestones obtained before and after spinal cord injury (SCI) with postinjury employment (PIE). Survey data were collected from 1,362 adults younger than 65, with traumatic SCI of at least 1 year duration who were not currently attending school. The sole outcome was obtaining PIE--whether the…
Gilad, Dvorit; Lavee, Yoav
This article describes the cognitive schemata of couples' support relationships among 65 couples in which the husband had a long-term spinal cord injury and 65 couples without disability. The structure of the support relations schemata were examined by means of smallest-space analysis. Similarities between men and women in couples with and without…
Hampton, Nan Zhang
Explores the relationship between self-efficacy beliefs and the quality of life in Chinese individuals with spinal cord injuries. Also examines whether health status and demographic variables correlated with the quality of life in this population. Results are discussed in line with the Chinese culture and its influences on the psychosocial…
NIDRR Consensus Statement, 1992
A 1992 Urinary Tract Infection Consensus Validation Conference brought together researchers, clinicians, and consumers to arrive at consensus on the best practices for preventing and treating urinary tract infections (UBI) in people with spinal cord injuries; the risk factors and diagnostic studies that should be done; indications for antibiotic…
Johnson, Michael D; Frigon, Alain; Hurteau, Marie-France; Cain, Charlette; Heckman, Charles J
In this study we evaluate temporal summation (wind-up) of reflexes in select distal and proximal hindlimb muscles in response to repeated stimuli of the distal tibial or superficial peroneal nerves in cats 1 month following complete spinal transection. This report is a continuation of our companion paper on reflex wind-up in the intact and acutely spinalized cat. To evaluate reflex wind-up in both studies we recorded EMG signals from the following left hindlimb muscles: lateral gastrocnemius (LG), tibialis anterior (TA), semitendinosus (ST) and sartorius (Srt) in response to 10 electrical pulses to the tibial or superficial peroneal nerves. Two distinct components of the reflex responses were considered, a short latency compound action potential (CAP) and a longer duration bout of sustained activity (SA). These two response types were shown to be differentially modified by acute spinal injury in our companion paper (Frigon, Johnson et al. 2012). We show that these responses exhibit continued plasticity during the 1-month recovery period following acute spinalization. During this early chronic phase, wind-up of SA responses returned to pre-injury levels in one muscle, the ST, but remained depressed in all other muscles tested. In contrast CAP response amplitudes, which were initially potentiated following acute transection, returned to pre-injury levels in all muscles except for Srt, which continued to show marked increase. These findings illustrate that spinal elements exhibit considerable plasticity during the recovery process following spinal injury and highlight the importance of considering SA and CAP responses as distinct phenomena with unique underlying neural mechanisms.
Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire
Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis. Theoretically, this strategy could also restore control over leg muscle activity for walking. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges. Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion. Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for
Solis, Leandro R.; Twist, Elizabeth; Seres, Peter; Thompson, Richard B.
Deep tissue injury (DTI) is a severe medical complication that commonly affects those with spinal cord injury. It is caused by prolonged external loading of the muscles, entrapping them between a bony prominence and the support surface. The entrapment causes excessive mechanical deformation and increases in interstitial pressure, leading to muscle breakdown deep around the bony prominences. We proposed the use of intermittent electrical stimulation (IES) as a novel prophylactic method for the prevention of DTI. In this study, we assessed the long-term effectiveness of this technique in pigs that had received a partial spinal cord injury that paralyzed one hindlimb. The pigs recovered for 2 wk postsurgery, and subsequently, their paralyzed limbs were loaded to 25% of their body weights 4 h/day for 4 consecutive days each week for 1 mo. One group of pigs (n = 3) received IES during the loading, whereas another group (n = 3) did not. DTI was quantified using magnetic resonance imaging (MRI) and postmortem histology. In the group that did not receive IES, MRI assessments revealed signs of tissue damage in 48% of the volume of the loaded muscle. In the group that did receive IES, only 8% of the loaded muscle volume showed signs of tissue damage. Similar findings were found through postmortem histology. This study demonstrates, for the first time, that IES may be an effective technique for preventing the formation of DTI in loaded muscles after spinal cord injury. PMID:23172030
Shaikh, Nissar; Rhaman, M. A.; Raza, Ali; Shabana, Adel; Malstrom, Mahommad Faisal; Al-Sulaiti, Ghanem
Background: High spinal cord injury (HSCI) is one of the devastating traumatic injuries. 80% of these patients are young male, and 93% will have major neurological disabilities. There is a paucity of literature about prolonged bradycardia in HSCI patients. The aim of this study was to know the prevalence, risk factors, precipitating factors for prolonged bradycardia in the HSCI patients. Materials and Methods: All patients who were admitted to the Intensive Care Unit (ICU) of a tertiary hospital, with spinal cord injury above level of dorsal (D4) were enrolled in this study prospectively. Patient's demographic data, mechanism, level and type of spinal injury, associated injuries, injury severity score (ISS), spinal shock, vasopressors used, time of occurrence of bradycardia, treatment for bradycardia, precipitating as well as risk factors and outcome were recorded. Results: During the study period, a total of 138 patients were admitted to the ICU with HSCI. Majority of patients were male. The most frequently associated injury in these patients was skeletal fractures (38.4%). Most common complication was pneumonia 56 (41%). Forty-five (33%) of the total patients had prolonged bradycardia; 87% of these patients had pneumonia when bradycardia occurred. 53.4% had cardiac asystole. 29 (21%) patients had bradycardia at the time of endotracheal suctioning, whereas 27 (20%) patients developed bradycardia at the time of positioning. Majority of the patients were managed conservatively. Those HSCI patients who developed prolonged bradycardia, their ISS score was statistically higher, ICU and hospital stay was significantly higher compared with those HSCI patient who did not have prolonged bradycardia. Multivariate analysis revealed that hypotension on admission; pneumonia, and tracheostomy were risk factors for the development of prolonged bradycardia in HSCI patients. Conclusion: Prolonged bradycardia was associated with significantly higher incidence of asystole
Adhikary, Sabina; Li, Hongbo; Heller, Joshua; Skarica, Mario; Zhang, Ming; Ganea, Doina
Abstract The goal of the current investigation was to evaluate the mechanisms through which administration of a selective cannabinoid-2 (CB2) agonist (O-1966) modifies inflammatory responses and helps to improve function following spinal cord injury. A comparison of motor function, autonomic function, and inflammatory responses was made between animals treated with O-1966 (5 mg/kg IP) and animals treated with vehicle 1 h and 24 h following contusion injury to the spinal cord. Motor function was significantly improved in the treated animals at each time point during the 14 days of evaluation. The percentage of animals able to spontaneously void their bladder was also greater over the entire study period in the group treated with the selective CB2 agonist. Seven days following injury there was a significant reduction in both hematopoietic and myeloid cell invasion of the spinal cord, and a reduction in the number of immunoreactive microglia. The results of the evaluation of chemokine/cytokine expression and inflammatory cell invasion also demonstrated a significant effect of treatment on inflammatory reactions following injury. Two days after injury, animals treated with O-1966 had significant reductions in CXCL-9 and CXCL-11, and dramatic reductions in IL-23p19 expression and its receptor IL-23r. Treatment with O-1966 also caused inhibition of toll-like receptor expression (TLR1, TLR4, TLR6 and TLR7) following injury. These results demonstrate that the improvement in motor and autonomic function resulting from treatment with a selective CB2 agonist is associated with a significant effect on inflammatory responses in the spinal cord following injury. PMID:21970496
Yisheng, W; Fuying, Z; Limin, W; Junwei, Li; Guofu, P; Weidong, W
Background: Traumatic cervical spinal cord injury with subaxial fracture and dislocation not only indicates a highly unstable spine but can also induce life-threatening complications. This makes first aid critically important before any definitive operative procedure is undertaken. The present study analyzes the various first aid measures and operative procedures for such injury. Materials and Methods: Two hundred and ninety-five patients suffered from cervical spinal cord injury with fracture and dislocation. The average period between injury and admission was 4.5 days (range 5 h-12 weeks). The injury includes burst fractures (n = 90), compression fractures with herniated discs (n = 50), fractures and dislocation (n = 88) and pure dislocation (n = 36). Other injuries including developmental spinal canal stenosis and/or multi-segment spinal cord compression associated with trauma (n = 12), lamina fractures compressing the spinal cord (n = 6), ligament injuries (n = 7) and hematoma (n = 6) were observed in the present study. The injury level was C4 (n = 17), C5 (n = 29), C6 (n = 39), C7 (n = 35), C4-5 (n = 38), C5-6 (n = 58), C6-7 (n = 49), C4-6 (n = 16) and C5-7 (n = 14). According to the Frankel grading system, grade A was observed in 20 cases, grade B in 91, grade C in 124 and grade D in 60. One hundred and eighteen (40%) patients had a high fever and difficulty in breathing on presentation. First aid measures included early reduction and immobilization of the injured cervical spine, controlling the temperature, breathing support, and administration of high-dose methylprednisolone within eight hours of the injury (n = 12) and administration of dehydration and neurotrophy medicine. Oxygen support was given and tracheotomy was performed for patients with serious difficulty in breathing. Measures were taken to prevent bedsores and infections of the respiratory and urological systems. Two hundred and thirty six patients were treated with anterior decompression, 31
Aquarone, Rita Lacerda; Faro, Ana Cristina Mancussi e
Studies evaluating the Quality of Life of individuals with spinal cord injury using different research tools demonstrate that the Quality of Life scores are considered low both in national and international studies. The objective of this review was to characterize the international scientific production about the most used scales to assess Quality of Life in patients with spinal cord injury. We examined articles on Quality of Life of patients with spinal cord injury published over the last 5 years and indexed in the National Library of Medicine (PUBMED). During this period, 28 articles met the inclusion criteria. Eleven studies were conducted in the United States, five articles were published in Australia, and four in Canada. Brazil, France, Holland, India, Japan, Norway, Singapore and Switzerland contributed with one study each. The scientific articles were published in 13 high impact factor journals. Seven different instruments to assess Quality of Life were used in the studies: Satisfaction with Life Scale, Short Form (36) Health Survey, The Brief Version of the WHO Quality of Life Questionnaire (WHOQOL-BREF), Comprehensive Quality of Life Scale, Life Situation Questionnaire-Revised, Quality of Well-Being Scale and the SF-12® Health Survey. The articles examined underscore the impact of spinal cord injury in the Quality of Life of patients, demonstrating how this condition impairs their lives, mainly socially, but followed by the physical aspects. Despite the studies have different goals they all acknowledge that further studies are necessary in order to determine the Quality of Life of patients with spinal cord injury. Specific instruments should be chosen or developed and validated in order to fulfill this purpose.
Aquarone, Rita Lacerda; Faro, Ana Cristina Mancussi e
ABSTRACT Studies evaluating the Quality of Life of individuals with spinal cord injury using different research tools demonstrate that the Quality of Life scores are considered low both in national and international studies. The objective of this review was to characterize the international scientific production about the most used scales to assess Quality of Life in patients with spinal cord injury. We examined articles on Quality of Life of patients with spinal cord injury published over the last 5 years and indexed in the National Library of Medicine (PUBMED). During this period, 28 articles met the inclusion criteria. Eleven studies were conducted in the United States, five articles were published in Australia, and four in Canada. Brazil, France, Holland, India, Japan, Norway, Singapore and Switzerland contributed with one study each. The scientific articles were published in 13 high impact factor journals. Seven different instruments to assess Quality of Life were used in the studies: Satisfaction with Life Scale, Short Form (36) Health Survey, The Brief Version of the WHO Quality of Life Questionnaire (WHOQOL-BREF), Comprehensive Quality of Life Scale, Life Situation Questionnaire-Revised, Quality of Well-Being Scale and the SF-12® Health Survey. The articles examined underscore the impact of spinal cord injury in the Quality of Life of patients, demonstrating how this condition impairs their lives, mainly socially, but followed by the physical aspects. Despite the studies have different goals they all acknowledge that further studies are necessary in order to determine the Quality of Life of patients with spinal cord injury. Specific instruments should be chosen or developed and validated in order to fulfill this purpose PMID:25003935
Eminović, Fadilj; Dopsaj, Milivoj; Pavlović, Dragan; Arsić, Sladjana; Otašević, Jadranka
Abstract Objectives Studying the quality of life of people with a spinal cord injury is of great importance as it allows the monitoring of both functioning and adaptation to disability. The aim of this study was to determine the difference between persons with a spinal cord injury involved in sports activities and those not involved in sports activities in relation to their quality of life and the presence of secondary health conditions (pressure ulcers, urinary infections, muscle spasms, osteoporosis, pain, kidney problems-infections, calculosis and poor circulation). Methods The study included a total of 44 participants with spinal cord injury-paraplegia of both genders; 26 of them were athletes and 18 were not athletes. The athletes were training actively for the last two years, minimally 2-3 times per week. A specially designed questionnaire, medical documentation and the Spinal Cord Injury Quality of Life Questionnaire (SCI QL-23) were used for research purposes. Chi-square test was used to analyze the differences between the groups, while multiple analysis of variance (MANOVA) was used to determine the differences between the sets of variables. Results Among the participants, the athletes perceived higher quality of life than the non-athletes (male gender p<0.001 and female gender p<0.05). Regarding secondary health conditions, the athletes reported the presence of less pain (p=0.034) and a subjective feeling of better circulation (p=0.023). Conclusion The implementation of sports activities significantly improves quality of life in the population of people with spinal cord injury-paraplegia. However, sports activities only partially affect secondary health conditions. PMID:27284378
Zbogar, Dominik; Eng, Janice J; Miller, William C; Krassioukov, Andrei V; Verrier, Mary C
Objectives: To assess the test–retest reliability and convergent validity of daily physical activity measures during inpatient spinal cord injury rehabilitation. Design: Observational study. Setting: Two inpatient spinal cord injury rehabilitation centres. Subjects: Participants (n = 106) were recruited from consecutive admissions to rehabilitation. Methods: Physical activity during inpatient spinal cord injury rehabilitation stay was recorded on two days via (1) wrist accelerometer, (2) hip accelerometer if ambulatory, and (3) self-report (Physical Activity Recall Assessment for People with Spinal Cord Injury questionnaire). Spearman’s correlations and Bland–Altman plots were utilized for test–retest reliability. Correlations between physical activity measures and clinical measures (functional independence, hand function, and ambulation) were performed. Results: Correlations for physical activity measures between Day 1 and Day 2 were moderate to high (ρ = 0.53–0.89). Bland–Altman plots showed minimal bias and more within-subject differences in more active individuals and wide limits of agreement. None of these three physical activity measures correlated with one another. A moderate correlation was found between wrist accelerometry counts and grip strength (ρ = 0.58) and between step counts and measures of ambulation (ρ = 0.62). Functional independence was related to wrist accelerometry (ρ = 0.70) and step counts (ρ = 0.56), but not with self-report. Conclusion: The test–retest reliability and convergent validity of the instrumented measures suggest that wrist and hip accelerometers are appropriate tools for use in research studies of daily physical activity in the spinal cord injury rehabilitation setting but are too variable for individual use. PMID:27635252
Mac-Thiong, Jean-Marc; Roy-Beaudry, Marjolaine; Sosa, Jose Felix; Labelle, Hubert
Abstract Spinal Cord Injury (SCI) in the pediatric population is relatively rare but carries significant psychological and physiological consequences. An interdisciplinary group of experts composed of medical and surgical specialists treating patients with SCI formulated the following questions: 1) What is the epidemiology of pediatric spinal cord injury and fractures?; 2) Are there unique features of pediatric SCI which distinguish the pediatric SCI population from adult SCI?; 3) Is there evidence to support the use of neuroprotective approaches, including hypothermia and steroids, in the treatment of pediatric SCI? A systematic review of the literature using multiple databases was undertaken to evaluate these three specific questions. A search strategy composed of specific search terms (Spinal Cord Injury, Paraplegia, Quadriplegia, tetraplegia, lapbelt injuries, seatbelt injuries, cervical spine injuries and Pediatrics) returned over 220 abstracts that were evaluated and by two observers. Relevant abstracts were then evaluated and papers were graded using the Downs and Black method. A table of evidence was then presented to a panel of experts using a modified Delphi approach and the following recommendation was then formulated using a consensus approach: Pediatric patients with traumatic SCI have different mechanisms of injury and have a better neurological recovery potential when compared to adults. Patients with SCI before their adolescent growth spurt have a high likelihood of developing scoliosis. Because of these differences, traumatic SCI should be highly suspected in the presence of abnormal neck or neurological exam, a high-risk mechanism of injury or a distracting injury even in the absence of radiological anomaly. PMID:21501096
Lieutaud, Thomas; Ndiaye, Amina; Frost, Fanny; Chiron, Mireille
Fatalities or injuries following motorized and non-motorized vehicle accidents (MNMVA) are reported by police or health care systems. However, limited data exist for spinal injuries. Using an epidemiological database of road accidents occurring in a defined geographic area, we measured the incidence of major spinal trauma (MST, Abbreviated Injury Scale [AIS] score 2 or more), spinal cord injury (SCI, AIS score 4 or more), and associated lesions over a 10-year period (1997-2006). Among the 97,341 victims included, 21,623 (22.2%) suffered spinal trauma, but only 1523 (1.6%) and 144 (0.2%) sustained an MST or SCI, respectively, and among those 10% and 43% died, respectively, before reaching hospital facilities. Men were more likely to have SCI and die. Cervical injuries were more frequently observed for SCI (58%) than for MST (39%; p < 0.001). Motorcyclists were overrepresented in SCI (33%) compared to MST (21%; p < 0.001), and were at significant risk for fatality. Non-restrained car occupants were at risk of MST and SCI, whereas motorcyclists wearing helmets were not. The chest was the most frequently-injured body region. Nearly half of MNMVA victims suffering SCI die quickly after the crash. Young age, male gender, a motorcyclist, and non-restrained car occupant were risk factors for serious injury. These groups should be targeted in specific programs to decrease fatalities, spinal trauma, and SCI after MNMVA.
Popovich, Phillip G; Tovar, C Amy; Lemeshow, Stanley; Yin, Qin; Jakeman, Lyn B
The goal of the current manuscript was to replicate published data that show intrathecal infusions of Taxol® (paclitaxel), an anti-neoplastic microtubule stabilizing agent, reduce fibrogliotic scarring caused by a dorsal spinal hemisection (DHx) injury and increase functional recovery and growth of serotonergic axons after moderate spinal contusion injury. These experiments were completed as part of an NIH-NINDS contract entitled "Facilities of Research Excellence in Spinal Cord Injury (FORE-SCI) - Replication". Here, data are presented that confirm the anti-scarring effects of Taxol after DHx injury; however, Taxol did not confer neuroprotection or promote serotonergic axon growth nor did it improve functional recovery in a model of moderate spinal contusion injury. Thus, only partial replication was achieved. Possible explanations for disparate results in our studies and published data are discussed.
d'Hemecourt, Pierre A; Luke, Anthony
Young aesthetic athletes require special understanding of the athletic biomechanical demands peculiar to each sport. The performance of these activities may impart specific biomechanical stresses and subsequent injury patterns. The clinician must understand these aspects as well as the spinal changes that occur with growth when many of these injuries often occur. Further, athletes, parents, coaches, and healthcare providers must be sensitive to the overall aspects of the athlete, including nutrition, overtraining, adequate recovery, proper technique, and limiting repetition of difficult maneuvers to minimize injuries.
Structural discontinuity in the spinal cord after injury results in a disruption in the impulse conduction resulting in loss of various bodily functions depending upon the level of injury. This article presents a summary of the scientific research employing electrical stimulation as a means for anatomical or functional recovery for patients suffering from spinal cord injury. Electrical stimulation in the form of functional electrical stimulation (FES) can help facilitate and improve upper/lower limb mobility along with other body functions lost due to injury e.g. respiratory, sexual, bladder or bowel functions by applying a controlled electrical stimulus to generate contractions and functional movement in the paralysed muscles. The available rehabilitative techniques based on FES technology and various Food and Drug Administration, USA approved neuroprosthetic devices that are in use are discussed. The second part of the article summarises the experimental work done in the past 2 decades to study the effects of weakly applied direct current fields in promoting regeneration of neurites towards the cathode and the new emerging technique of oscillating field stimulation which has shown to promote bidirectional regeneration in the injured nerve fibres. The present article is not intended to be an exhaustive review but rather a summary aiming to highlight these two applications of electrical stimulation and the degree of anatomical/functional recovery associated with these in the field of spinal cord injury research. PMID:18677518
Kabu, Shushi; Gao, Yue; Kwon, Brian K; Labhasetwar, Vinod
Spinal cord injury (SCI) results in devastating neurological and pathological consequences, causing major dysfunction to the motor, sensory, and autonomic systems. The primary traumatic injury to the spinal cord triggers a cascade of acute and chronic degenerative events, leading to further secondary injury. Many therapeutic strategies have been developed to potentially intervene in these progressive neurodegenerative events and minimize secondary damage to the spinal cord. Additionally, significant efforts have been directed toward regenerative therapies that may facilitate neuronal repair and establish connectivity across the injury site. Despite the promise that these approaches have shown in preclinical animal models of SCI, challenges with respect to successful clinical translation still remain. The factors that could have contributed to failure include important biologic and physiologic differences between the preclinical models and the human condition, study designs that do not mirror clinical reality, discrepancies in dosing and the timing of therapeutic interventions, and dose-limiting toxicity. With a better understanding of the pathobiology of events following acute SCI, developing integrated approaches aimed at preventing secondary damage and also facilitating neuroregenerative recovery is possible and hopefully will lead to effective treatments for this devastating injury. The focus of this review is to highlight the progress that has been made in drug therapies and delivery systems, and also cell-based and tissue engineering approaches for SCI.
Aguilar-Cevallos, Jorge; Silva-Garcia, Raul; Ibarra, Antonio
Spinal cord injury results in a life-disrupting series of deleterious interconnected mechanisms encompassed by the primary and secondary injury. These events are mediated by the upregulation of genes with roles in inflammation, transcription, and signaling proteins. In particular, cytokines and growth factors are signaling proteins that have important roles in the pathophysiology of SCI. The balance between the proinflammatory and anti-inflammatory effects of these molecules plays a critical role in the progression and outcome of the lesion. The excessive inflammatory Th1 and Th17 phenotypes observed after SCI tilt the scale towards a proinflammatory environment, which exacerbates the deleterious mechanisms present after the injury. These mechanisms include the disruption of the spinal cord blood barrier, edema and ion imbalance, in particular intracellular calcium and sodium concentrations, glutamate excitotoxicity, free radicals, and the inflammatory response contributing to the neurodegenerative process which is characterized by demyelination and apoptosis of neuronal tissue. PMID:27418745
Iversen, P O; Hjeltnes, N; Holm, B; Flatebo, T; Strom-Gundersen, I; Ronning, W; Stanghelle, J; Benestad, H B
The bone marrow is supplied with both sensory and autonomic neurons, but their roles in regulating hematopoietic and immunocompetent cells are unknown. Leukocyte growth and activity in patients with stable and complete spinal cord injuries were studied. The innervation of the bone marrow below the injury level lacked normal supraspinal activity, that is, a decentralized bone marrow. Lymphocyte functions were markedly decreased in injured patients. Long-term colony formation of all hematopoietic cell lineages, including dendritic cells, by decentralized bone marrow cells was substantially reduced. It was concluded that nonspecific and adaptive lymphocyte-mediated immunity and growth of early hematopoietic progenitor cells are impaired in patients with spinal cord injuries. Possibly, this reflects cellular defects caused by the malfunctioning neuronal regulation of immune and bone marrow function.
Huang, Qiuchen; Yu, Lili; Gu, Rui; Zhou, Yue; Hu, Chunying
[Purpose] The purpose of this study was to compare the effects of body weight-supported treadmill training (BWSTT) and robot-assisted rehabilitation (RAT) on bowel function in patients with spinal cord injury with respect to defecation time and defecation drug dose (enema). [Subjects] Twenty-four patients with spinal cord injury participated in the study. All subjects had an incomplete injury ranging from level T8 to L2. [Methods] The subjects were randomly divided into BWSTT and RAT groups. Walking training was provided to both groups for 20 minutes, four times a week, for one month. The defecation time and enema dose were measured before and after the experiment. [Results] The RAT group showed significant shortening of defecation time and decrease of enema dose. [Conclusion] The results demonstrated that significantly better improvement in bowel function can be achieved with RAT. PMID:26157223
Severe spinal cord injury (SCI) leads to devastating neurological deficits and disabilities, which necessitates spending a great deal of health budget for psychological and healthcare problems of these patients and their relatives. This justifies the cost of research into the new modalities for treatment of spinal cord injuries, even in developing countries. Apart from surgical management and nerve grafting, several other approaches have been adopted for management of this condition including pharmacologic and gene therapy, cell therapy, and use of different cell-free or cell-seeded bioscaffolds. In current paper, the recent developments for therapeutic delivery of stem and non-stem cells to the site of injury, and application of cell-free and cell-seeded natural and synthetic scaffolds have been reviewed.
Hess, Marika J.; Hough, Sigmund
This study focuses on the impact a spinal cord injury may have on achieving physical and emotional intimacy, and potential to maximize sexual ability and quality of life. Spinal cord injury is a traumatic, life-altering event that is usually associated with loss of motor and sensory function, as well as sexual impairment. At the time of injury, the individual is faced with devastating loss and an abundance of new information in a setting of extreme stress and challenge. In the acute rehabilitation setting, there is often a considerable void in providing education and resources regarding sexual concerns and needs. There is a positive relationship between sexual education and sexual activity. The impact of inadequate sexual counseling and education as a part of rehabilitation can be deleterious. PMID:22925747
Hayakawa, Kazuo; Haas, Christopher; Fischer, Itzhak
In the aftermath of spinal cord injury, glial restricted precursors (GRPs) and immature astrocytes offer the potential to modulate the inflammatory environment of the injured spinal cord and promote host axon regeneration. Nevertheless clinical application of cellular therapy for the repair of spinal cord injury requires strict quality-assured protocols for large-scale production and preservation that necessitates long-term in vitro expansion. Importantly, such processes have the potential to alter the phenotypic and functional properties and thus therapeutic potential of these cells. Furthermore, clinical use of cellular therapies may be limited by the inflammatory microenvironment of the injured spinal cord, altering the phenotypic and functional properties of grafted cells. This report simulates the process of large-scale GRP production and demonstrates the permissive properties of GRP following long-term in vitro culture. Furthermore, we defined the phenotypic and functional properties of GRP in the presence of inflammatory factors, and call attention to the importance of the microenvironment of grafted cells, underscoring the importance of modulating the environment of the injured spinal cord. PMID:27212899
BARROS, TARCÍSIO ELOY PESSOA; ARAUJO, FERNANDO FLORES DE; HIGINO, LUCAS DA PAZ; MARCON, RAPHAEL MARTUS; CRISTANTE, ALEXANDRE FOGAÇA
ABSTRACT Objective: To evaluate the effect of monosialoganglioside (GM-1) in spinal cord trauma patients seen in our service who have not been treated with methylprednisolone. Methods: Thirty patients with acute spinal cord trauma were randomly divided into two groups. In Group 1, patients received 200 mg GM-1 in the initial assessment and thereafter received 100 mg intravenous per day for 30 days and Group 2 (control) received saline. Patients were evaluated periodically (at 6 weeks, 6 months, one year and two years), using a standardized neurological assessment of the American Spinal Injury Association / International Spinal Cord Society. Results: The comparative statistical analysis of motor indices, sensitive indices for pain and touch according to the standardization of ASIA / ISCOS showed that the assessments at 6 weeks, 6 months and 2 years, GM-Group 1 patients had higher rates than the control group regarding sensitivity to pain and touch, with no statistically significant difference from the motor index. Conclusion: The functional assessment showed improvement in the sensitive indices of patients treated with GM1 after post-traumatic spinal cord injury compared to patients who received placebo. Level of Evidence IV, Prospective Case Studies Series. PMID:27217811
Ning, Guang-Zhi; Wu, Qiang; Li, Yu-Lin; Feng, Shi-Qing
Study design A systematic review. Background The number of traumatic spinal cord injury (TSCI) reports grows annually, especially in China and Korea. The epidemiological characteristics of TSCI in Asia differ from those in other countries. Thus, we compiled epidemiological factors from Asia to compare with those from other countries. Method We searched articles published in any language between January 1980 to December 2011 using the terms “spinal cord injury”, “traumatic spinal cord injury”, “epidemiology”, and “Asia”. The articles were reviewed for information regarding TSCI incidence, total cases, case criteria, case source, causes of injury, male/female ratio, mean age, prospective or retrospective, neurological level of injury, extent of injury, and America Spinal Injury Association Impairment Scale (AIS)/grade. Results Epidemiological data were extracted from 39 reports in the published literature that met the inclusion criteria. Only two studies reported prevalence rates. Incidence rates ranged from 12.06 to 61.6 per million. The average age ranged from 26.8 to 56.6 years old. Men were at higher risk than women. Motor vehicle collisions (MVCs) and falls were the main causes of TSCI. However, several countries reported war wounds as the major cause. The neurological level and extent of injury were mixed, and most patients were categorized as AIS/Frankel grade A. Conclusion TSCI is an important public health problem and a major cause of paralysis. We must understand the epidemiology to implement appropriate preventative measures. Asian epidemiology is different from that in other regions, so intervention measures must be established according to population-specific characteristics. PMID:22925749
Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I.; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew
Abstract With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996
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
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
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
Koehn, Liam M.; Noor, Natassya M.; Dong, Qing; Er, Sing-Yan; Rash, Lachlan D.; King, Glenn F.; Dziegielewska, Katarzyna M.; Saunders, Norman R.; Habgood, Mark D.
Tissue loss after spinal trauma is biphasic, with initial mechanical/haemorrhagic damage at the time of impact being followed by gradual secondary expansion into adjacent, previously unaffected tissue. Limiting the extent of this secondary expansion of tissue damage has the potential to preserve greater residual spinal cord function in patients. The acute tissue hypoxia resulting from spinal cord injury (SCI) activates acid-sensing ion channel 1a (ASIC1a). We surmised that antagonism of this channel should provide neuroprotection and functional preservation after SCI. We show that systemic administration of the spider-venom peptide PcTx1, a selective inhibitor of ASIC1a, improves locomotor function in adult Sprague Dawley rats after thoracic SCI. The degree of functional improvement correlated with the degree of tissue preservation in descending white matter tracts involved in hind limb locomotor function. Transcriptomic analysis suggests that PcTx1-induced preservation of spinal cord tissue does not result from a reduction in apoptosis, with no evidence of down-regulation of key genes involved in either the intrinsic or extrinsic apoptotic pathways. We also demonstrate that trauma-induced disruption of blood-spinal cord barrier function persists for at least 4 days post-injury for compounds up to 10 kDa in size, whereas barrier function is restored for larger molecules within a few hours. This temporary loss of barrier function provides a “ treatment window” through which systemically administered drugs have unrestricted access to spinal tissue in and around the sites of trauma. Taken together, our data provide evidence to support the use of ASIC1a inhibitors as a therapeutic treatment for SCI. This study also emphasizes the importance of objectively grading the functional severity of initial injuries (even when using standardized impacts) and we describe a simple scoring system based on hind limb function that could be adopted in future studies. PMID:28105306
Cloud, Beth A.; Ball, Bret G.; Chen, Bingkun; Knight, Andrew M.; Hakim, Jeffrey S.; Ortiz, Ana M.; Windebank, Anthony J.
Techniques used to produce partial spinal cord injuries in animal models have the potential for creating variability in lesions. The amount of tissue affected may influence the functional outcomes assessed in the animals. The recording of somatosensory evoked potentials (SSEPs) may be a valuable tool for assessing the extent of lesion applied in animal models of traumatic spinal cord injury (SCI). Intraoperative tibial SSEP recordings were assessed during surgically induced lateral thoracic hemisection SCI in Sprague-Dawley rats. The transmission of SSEPs, or lack thereof, was determined and compared against the integrity of the dosal funiculi on each side of the spinal cord upon histological sectioning. An association was found between the presence of an SSEP signal and presence of intact dorsal funiculus tissue. The relative risk is 4.50 (95% confidence interval: 1.83 to 11.08) for having an intact dorsal funiculus when the ipsilateral SSEP was present compared to when it was absent. Additionally, the amount of spared spinal cord tissue correlates with final functional assessments at nine weeks post injury: BBB (linear regression, R2 = 0.618, p <0.001) and treadmill test (linear regression, R2 = 0.369, p = 0.016). Therefore, we propose intraoperative SSEP monitoring as a valuable tool to assess extent of lesion and reduce variability between animals in experimental studies of SCI. PMID:22960163
Ruven, Carolin; Li, Wen; Li, Heng; Wong, Wai-Man; Wu, Wutian
Injuries to peripheral nerves are frequent in serious traumas and spinal cord injuries. In addition to surgical approaches, other interventions, such as cell transplantation, should be considered to keep the muscles in good condition until the axons regenerate. In this study, E14.5 rat embryonic spinal cord fetal cells and cultured neural progenitor cells from different spinal cord segments were injected into transected musculocutaneous nerve of 200–300 g female Sprague Dawley (SD) rats, and atrophy in biceps brachii was assessed. Both kinds of cells were able to survive, extend their axons towards the muscle and form neuromuscular junctions that were functional in electromyographic studies. As a result, muscle endplates were preserved and atrophy was reduced. Furthermore, we observed that the fetal cells had a better effect in reducing the muscle atrophy compared to the pure neural progenitor cells, whereas lumbar cells were more beneficial compared to thoracic and cervical cells. In addition, fetal lumbar cells were used to supplement six weeks delayed surgical repair after the nerve transection. Cell transplantation helped to preserve the muscle endplates, which in turn lead to earlier functional recovery seen in behavioral test and electromyography. In conclusion, we were able to show that embryonic spinal cord derived cells, especially the lumbar fetal cells, are beneficial in the treatment of peripheral nerve injuries due to their ability to prevent the muscle atrophy. PMID:28264437
Ruven, Carolin; Li, Wen; Li, Heng; Wong, Wai-Man; Wu, Wutian
Injuries to peripheral nerves are frequent in serious traumas and spinal cord injuries. In addition to surgical approaches, other interventions, such as cell transplantation, should be considered to keep the muscles in good condition until the axons regenerate. In this study, E14.5 rat embryonic spinal cord fetal cells and cultured neural progenitor cells from different spinal cord segments were injected into transected musculocutaneous nerve of 200-300 g female Sprague Dawley (SD) rats, and atrophy in biceps brachii was assessed. Both kinds of cells were able to survive, extend their axons towards the muscle and form neuromuscular junctions that were functional in electromyographic studies. As a result, muscle endplates were preserved and atrophy was reduced. Furthermore, we observed that the fetal cells had a better effect in reducing the muscle atrophy compared to the pure neural progenitor cells, whereas lumbar cells were more beneficial compared to thoracic and cervical cells. In addition, fetal lumbar cells were used to supplement six weeks delayed surgical repair after the nerve transection. Cell transplantation helped to preserve the muscle endplates, which in turn lead to earlier functional recovery seen in behavioral test and electromyography. In conclusion, we were able to show that embryonic spinal cord derived cells, especially the lumbar fetal cells, are beneficial in the treatment of peripheral nerve injuries due to their ability to prevent the muscle atrophy.
An essential item in the development of this project was the availability of the artificial gravity simulator (AGS). At the termination of that grant in 1994, the AGS was dismantled and transferred to NASA Johnson Space Center. It took over two years for the AGS to be re-assembled and re-certified for use. As a consequence of the non-availability of the AGS for two years, there was a considerable delay in implementing the various phases of the project. The subjects involved in the study were eight healthy able bodied subjects and twelve with spinal cord injury. After analysis of the data collected on these subjects, six of the healthy able bodied subjects and three of the sub ects with spinal cord injury were found to qualify for the study. This report gives the results of four subjects only, two healthy able bodied and two spinal cord injured subjects because the period of the grant (1 year) and its extension (1 year) expired before additional subjects could be studied. The principal objective of the study was to conduct a series of experiments to demonstrate the feasibility of utilizing artificial gravity to assist in the physical rehabilitation of persons with spinal cord injuries.
Bolshakov, I. N.; Sergienko, V. I.; Kiselev, S. L.; Lagarkova, M. A.; Remigaylo, A. A.; Mihaylov, A. A.; Prokopenko, S. V.
In the treatment of patients with complicated spinal cord injury the Russian Health spends about one million rubles for each patient in the acute and the interim period after the injury. The number of complicated spinal cord injury is different in geographical areas Russian Federation from 30 to 50 people per 1 million that is affected by the year 5600. Applied to the present surgical and pharmacological techniques provide unsatisfactory results or minimally effective treatment. Transplantation of 100 thousand neuronal mouse predecessors (24 rats) or human neuronal predecessors (18 rats) in the anatomical gap rat spinal cord, followed by analysis of neurological deficit. The neuro-matrix implantation in the rat spinal cord containing 100 thousand neuronal precursors hESC, repeatable control neuro-matrix transplantation, non-cell mass, eliminating neurological deficit for 14 weeks after transplantation about 5-9 points on the scale of the BBB. The cultivation under conditions in vitro human induced pluripotent stem cells on collagen-chitosan matrix (hIPSC) showed that neurons differentiated from induced pluripotent stem cells grown on scaffolds as compact groups and has no neurites. Cells do not penetrate into the matrix during long-term cultivation and formed near the surface of the spherical structures resembling neurospheres. At least 90% of the cells were positive for the neuronal marker tubulin b3. Further studies should be performed to examine the compatibility of neuronal cultures and matrices.
Cloud, Beth A; Ball, Bret G; Chen, Bingkun K; Knight, Andrew M; Hakim, Jeffrey S; Ortiz, Ana M; Windebank, Anthony J
Techniques used to produce partial spinal cord injuries in animal models have the potential for creating variability in lesions. The amount of tissue affected may influence the functional outcomes assessed in the animals. The recording of somatosensory evoked potentials (SSEPs) may be a valuable tool for assessing the extent of lesion applied in animal models of traumatic spinal cord injury (SCI). Intraoperative tibial SSEP recordings were assessed during surgically induced lateral thoracic hemisection SCI in Sprague-Dawley rats. The transmission of SSEPs, or lack thereof, was determined and compared against the integrity of the dorsal funiculi on each side of the spinal cord upon histological sectioning. An association was found between the presence of an SSEP signal and presence of intact dorsal funiculus tissue. The relative risk is 4.50 (95% confidence interval: 1.83-11.08) for having an intact dorsal funiculus when the ipsilateral SSEP was present compared to when it was absent. Additionally, the amount of spared spinal cord tissue correlates with final functional assessments at nine weeks post injury: BBB (linear regression, R²=0.618, p<0.001) and treadmill test (linear regression, R²=0.369, p=0.016). Therefore, we propose intraoperative SSEP monitoring as a valuable tool to assess extent of lesion and reduce variability between animals in experimental studies of SCI.
Shin, Ji Cheol; Kim, Ji Yong; Park, Han Kyul
Objective To determine the effect of robotic-assisted gait training (RAGT) compared to conventional overground training. Methods Sixty patients with motor incomplete spinal cord injury (SCI) were included in a prospective, randomized clinical trial by comparing RAGT to conventional overground training. The RAGT group received RAGT three sessions per week at duration of 40 minutes with regular physiotherapy in 4 weeks. The conventional group underwent regular physiotherapy twice a day, 5 times a week. Main outcomes were lower extremity motor score of American Spinal Injury Association impairment scale (LEMS), ambulatory motor index (AMI), Spinal Cord Independence Measure III mobility section (SCIM3-M), and walking index for spinal cord injury version II (WISCI-II) scale. Results At the end of rehabilitation, both groups showed significant improvement in LEMS, AMI, SCIM3-M, and WISCI-II. Based on WISCI-II, statistically significant improvement was observed in the RAGT group. For the remaining variables, no difference was found. Conclusion RAGT combined with conventional physiotherapy could yield more improvement in ambulatory function than conventional therapy alone. RAGT should be considered as one additional tool to provide neuromuscular reeducation in patient with incomplete SCI. PMID:25566469
Jongen, Joost L. M.; Smits, Helwin; Pederzani, Tiziana; Bechakra, Malik; Hossaini, Mehdi; Koekkoek, Sebastiaan K.; Huygen, Frank J. P. M.; De Zeeuw, Chris I.; Holstege, Jan C.; Joosten, Elbert A. J.
Nerve injury may cause neuropathic pain, which involves hyperexcitability of spinal dorsal horn neurons. The mechanisms of action of spinal cord stimulation (SCS), an established treatment for intractable neuropathic pain, are only partially understood. We used Autofluorescent Flavoprotein Imaging (AFI) to study changes in spinal dorsal horn metabolic activity. In the Seltzer model of nerve-injury induced pain, hypersensitivity was confirmed using the von Frey and hotplate test. 14 Days after nerve-injury, rats were anesthetized, a bipolar electrode was placed around the affected sciatic nerve and the spinal cord was exposed by a laminectomy at T13. AFI recordings were obtained in neuropathic rats and a control group of naïve rats following 10 seconds of electrical stimulation of the sciatic nerve at C-fiber strength, or following non-noxious palpation. Neuropathic rats were then treated with 30 minutes of SCS or sham stimulation and AFI recordings were obtained for up to 60 minutes after cessation of SCS/sham. Although AFI responses to noxious electrical stimulation were similar in neuropathic and naïve rats, only neuropathic rats demonstrated an AFI-response to palpation. Secondly, an immediate, short-lasting, but strong reduction in AFI intensity and area of excitation occurred following SCS, but not following sham stimulation. Our data confirm that AFI can be used to directly visualize changes in spinal metabolic activity following nerve injury and they imply that SCS acts through rapid modulation of nociceptive processing at the spinal level. PMID:25279562
D'Amico, Jessica M.; Condliffe, Elizabeth G.; Martins, Karen J. B.; Bennett, David J.; Gorassini, Monica A.
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
Khurana, Seema R; Garg, Deep S
Muscle spasms and spasticity constitute a significant problem in patients with spinal cord injury, interfering with rehabilitation and leading to impairments in quality of life in addition to medical complications. Administration of intrathecal baclofen (ITB) is indicated when spasticity continues to produce a clinical disability despite trials of oral treatments and other alternatives in patients who have functional goals and/or pain without contractures. Severe spasticity of spinal origin has been shown to respond dramatically to long-term ITB when used in appropriate patients with spasticity.
Dai, Haining; MacArthur, Linda; McAtee, Marietta; Hockenbury, Nicole; Tidwell, J. Lille; McHugh, Brian; Mansfield, Kevin; Finn, Tom; Hamers, Frank P.T.
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
Anderson, Kim D; Guest, James D; Dietrich, W Dalton; Bunge, Mary Bartlett; Curiel, Rosie; Dididze, Marine; Green, Barth A; Khan, Aisha; Pearse, Damien D; Saraf-Lavi, Efrat; Widerström-Noga, Eva; Wood, Patrick; Levi, Allan D
The rationale for implantation of autologous human Schwann cells (SCs) in persons with subacute spinal cord injury (SCI) is based on evidence that transplanted SCs are neuroprotective, support local axonal plasticity, and are capable of myelinating axons. A Phase I clinical trial was conducted to evaluate the safety of autologous human SC transplantation into the injury epicenter of six subjects with subacute SCI. The trial was an open-label, unblinded, non-randomized, non-placebo controlled study with a dose escalation design and standard medical rehabilitation. Participants were paraplegics with neurologically complete, trauma-induced spinal lesions. Autologous SCs were cultured in vitro from a sural nerve harvested from each participant and injected into the epicenter of the spinal lesion. Outcome measures for safety were protocol compliance, feasibility, adverse events, stability of neurological level, absence of detectable mass lesion, and the emergence of clinically significant neuropathic pain or muscle spasticity no greater than expected for a natural course cohort. One year post-transplantation, there were no surgical, medical, or neurological complications to indicate that the timing or procedure for the cell transplantation was unsafe. There were no adverse events or serious adverse events related to the cell therapy. There was no evidence of additional spinal cord damage, mass lesion, or syrinx formation. We conclude that it is feasible to identify eligible candidates, appropriately obtain informed consent, perform a peripheral nerve harvest to obtain SCs within 5-30 days of injury, and perform an intra-spinal transplantation of highly purified autologous SCs within 4-7 weeks of injury.
Okada, Starlyn L M; Stivers, Nicole S; Stys, Peter K; Stirling, David P
Injured CNS axons fail to regenerate and often retract away from the injury site. Axons spared from the initial injury may later undergo secondary axonal degeneration. Lack of growth cone formation, regeneration, and loss of additional myelinated axonal projections within the spinal cord greatly limits neurological recovery following injury. To assess how central myelinated axons of the spinal cord respond to injury, we developed an ex vivo living spinal cord model utilizing transgenic mice that express yellow fluorescent protein in axons and a focal and highly reproducible laser-induced spinal cord injury to document the fate of axons and myelin (lipophilic fluorescent dye Nile Red) over time using two-photon excitation time-lapse microscopy. Dynamic processes such as acute axonal injury, axonal retraction, and myelin degeneration are best studied in real-time. However, the non-focal nature of contusion-based injuries and movement artifacts encountered during in vivo spinal cord imaging make differentiating primary and secondary axonal injury responses using high resolution microscopy challenging. The ex vivo spinal cord model described here mimics several aspects of clinically relevant contusion/compression-induced axonal pathologies including axonal swelling, spheroid formation, axonal transection, and peri-axonal swelling providing a useful model to study these dynamic processes in real-time. Major advantages of this model are excellent spatiotemporal resolution that allows differentiation between the primary insult