Concomitance of cervical intramedullary traumatic neuroma and cervical cord herniation in a tetraplegic woman.

PubMed

Su, Hui-Yi; Wu, Yung-Tsan; Liu, Ming-Ying; Lin, Yu-Chun; Chu, Heng-Yi; Chang, Shin-Tsu

2013-01-01

We present the first case of concomitant intramedullary traumatic neuroma and spinal cord herniation. A 57-year-old woman injured her cervical spine with subluxation and cord compression at the C5-C6 level. After the operation, the patient received intensive rehabilitation for one year with well response. Unfortunately, she experienced weakness and progressive numbness extending to all the limbs later. Cervical magnetic resonance imaging revealed spinal cord herniation at the C5-C6 level and pathology proved intramedullary traumatic neuroma. After the second operation, the paresthesia over the trunk and limbs persisted, and the patient was nearly totally assisted in her activities of daily living. The intramedullary traumatic neuroma and spinal cord herniation are rare causes in patients with spinal cord dysfunction. The case presented here indicates the possibility of the coexisting conditions leading to progressive neurologic deficits in patients with old spinal cord injury.

Sexual Functioning in Men Living with a Spinal Cord Injury–A Narrative Literature Review

PubMed Central

Sunilkumar, MM; Boston, Patricia; Rajagopal, MR

2015-01-01

Background: Sexual dysfunction is a major concern for Indian men living with a spinal cord injury Objectives: To examine the literature related to sexuality traumatic cord injury and its impact on sexual functioning. Materials and Methods: Databases using Cumulative Index to Nursing and Allied Health Literature (CINAHL) 2000–2012, Medline 1989–2012, Applied Social Sciences Index and Abstracts (ASSIA) 1989–2012 and Google Scholar were the search engines used used for literature review. Results: The search yielded a total of 457 articles and only 75 of them were found relevant. The minimum number of articles required to meet the inclusion criteria for this review was 25–30 articles. Out of the 75 articles, 33 were considered relevant or related to the topic of sexual functioning, spinal cord injury, and paraplegia. Six areas were identified: Sexual stigmatization, physiological barriers to sexual satisfaction, clinical aspects of sexual functioning, biomedical approaches to sexual dysfunction, partner satisfaction, and lack of accessibility to sexual education. Conclusion: Spinal cord injury and sexual functioning affects a large segment of the male Indian population, yet most current research focuses on quantitative measurement with the emphasis on ejaculatory dysfunction, orgasm impairment, incontinence, and other physiological dysfunction. Further research is needed to address the subjective accounts of patients themselves with respect to the emotional and social impact of sexual disability. This would help to identify the best possible outcomes for both treatment and rehabilitation. PMID:26600694

Cardiac dysfunctions following spinal cord injury

PubMed Central

Sandu, AM; Popescu, M; Iacobini, MA; Stoian, R; Neascu, C; Popa, F

2009-01-01

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 SCI. Each type of cardiac disturbance requires specific treatment. PMID:20108532

Involvement of the Spinal Cord in Mitochondrial Disorders.

PubMed

Finsterer, Josef; Zarrouk-Mahjoub, Sinda

2018-01-01

This review aims at summarising and discussing the current status concerning the clinical presentation, pathogenesis, diagnosis, and treatment of spinal cord affection in mitochondrial disorders (MIDs). A literature search using the database Pubmed was carried out by application of appropriate search terms and their combinations. Involvement of the spinal cord in MIDs is more frequent than anticipated. It occurs in specific and non-specific MIDs. Among the specific MIDs it has been most frequently described in LBSL, LS, MERRF, KSS, IOSCA, MIRAS, and PCH and only rarely in MELAS, CPEO, and LHON. Clinically, spinal cord involvement manifests as monoparesis, paraparesis, quadruparesis, sensory disturbances, hypotonia, spasticity, urinary or defecation dysfunction, spinal column deformities, or as transverse syndrome. Diagnosing spinal cord involvement in MIDs requires a thoroughly taken history, clinical exam, and imaging studies. Additionally, transcranial magnetic stimulation, somato-sensory-evoked potentials, and cerebro-spinal fluid can be supportive. Treatment is generally not at variance compared to the underlying MID but occasionally surgical stabilisation of the spinal column may be necessary. It is concluded that spinal cord involvement in MIDs is more frequent than anticipated but may be missed if cerebral manifestations prevail. Spinal cord involvement in MIDs may strongly determine the mobility of these patients.

Kainate and metabolic perturbation mimicking spinal injury differentially contribute to early damage of locomotor networks in the in vitro neonatal rat spinal cord.

PubMed

Taccola, G; Margaryan, G; Mladinic, M; Nistri, A

2008-08-13

Acute spinal cord injury evolves rapidly to produce secondary damage even to initially spared areas. The result is loss of locomotion, rarely reversible in man. It is, therefore, important to understand the early pathophysiological processes which affect spinal locomotor networks. Regardless of their etiology, spinal lesions are believed to include combinatorial effects of excitotoxicity and severe stroke-like metabolic perturbations. To clarify the relative contribution by excitotoxicity and toxic metabolites to dysfunction of locomotor networks, spinal reflexes and intrinsic network rhythmicity, we used, as a model, the in vitro thoraco-lumbar spinal cord of the neonatal rat treated (1 h) with either kainate or a pathological medium (containing free radicals and hypoxic/aglycemic conditions), or their combination. After washout, electrophysiological responses were monitored for 24 h and cell damage analyzed histologically. Kainate suppressed fictive locomotion irreversibly, while it reversibly blocked neuronal excitability and intrinsic bursting induced by synaptic inhibition block. This result was associated with significant neuronal loss around the central canal. Combining kainate with the pathological medium evoked extensive, irreversible damage to the spinal cord. The pathological medium alone slowed down fictive locomotion and intrinsic bursting: these oscillatory patterns remained throughout without regaining their control properties. This phenomenon was associated with polysynaptic reflex depression and preferential damage to glial cells, while neurons were comparatively spared. Our model suggests distinct roles of excitotoxicity and metabolic dysfunction in the acute damage of locomotor networks, indicating that different strategies might be necessary to treat the various early components of acute spinal cord lesion.

Clinical and imaging features of spinal cord type of neuro Behçet disease: A case report and systematic review.

PubMed

Liu, Hui-Miao; Dong, Ci; Zhang, Yong-Zhi; Tian, Ya-Yun; Chen, Hong-Xu; Zhang, Sai; Li, Na; Gu, Ping

2017-10-01

To investigate the clinical and MRI characteristics of spinal cord nerve Behçet's disease. One patient with spinal cord nerve Behçet's disease was admitted to our hospital at October 20, 2015. Spinal cord nerve Behçet's disease. Retrospective analysis was performed on such case as well as 16 cases of spinal cord nerve Behçet's disease reported in China or abroad. Seventeen cases of spinal cord type of neuro Behçet's disease include 13 men and 4 women, with an average age of onset of 34.8 years old. The mean time from Behçet's disease symptoms to spinal cord involvement were 10.8 years. The initial symptom in one case was spinal cord injury, and another 4 cases had a recurrence course. The most common performance of spinal cord injury was sensory disturbance (82.4%), following by weakness (76.5%), sphincter or sexual dysfunction (58.8%), and pain in back, backside of neck or lower chest (29.4%). The number of cells was slightly increased or the protein level was increased in cerebrospinal fluid test. And the water channel protein antibody and oligoclonal band of serum levels were all negative. The spinal cord injury involved more than 3 vertebral bodies in 10 cases, and involved more than half of spinal cord in sagittal plane in 8 cases. In acute stage, shock therapy with large dose of glucocorticoid was generally applied both in China and abroad. The clinical features of spinal cord nerve Behçet's disease were various, making it easily misdiagnosed. Longitudinal extensive transverse myelitis performs as a characteristic manifestation.

Effectiveness of Phosphodiesterase 5 Inhibitors in the Treatment of Erectile Dysfunction in Patients with Spinal Cord Trauma: Systematic Review and Meta-Analysis.

PubMed

García-Perdomo, Herney Andrés; Echeverría-García, Fernando; Tobías, Aurelio

2017-01-01

To determine the effectiveness of the Phosphodiesterase 5 (PDE5) Inhibitors for the treatment of erectile dysfunction in patients with spinal trauma. A systematic review and meta-analysis comparing PDE5 inhibitors versus placebo were carried out for clinical trials conducted between 1980 and 2014 that evaluated male patients older than 18 years, diagnosed with spinal cord trauma and erectile dysfunction. We designed a search strategy for Medline, CENTRAL, EMBASE and other electronic sources. Two investigators independently and blindly screened the studies for inclusion. A random effect meta-analysis was performed. Six studies involving 963 patients were included. Male patients over 18 years with ED attributable or subsequent to traumatic spinal cord injury (SCI) were included from these studies. In 4 of these studies, patients were randomized to the treatment group receiving sildenafil and the comparison group was placebo. Out of the remaining 2 trials, one compared tadalafil against the placebo and the other vardenafil versus placebo. The improvement on SCIs with PDE5 inhibitors was found to be large (standardized mean difference 0.71; 95% CI 0.39-1.03), with a high heterogeneity (I2 = 74.4%). PDE5 inhibitors are effective for the treatment of erectile dysfunction secondary to SCI. © 2016 S. Karger AG, Basel.

Vascular dysfunctions following spinal cord injury

PubMed Central

Popa, F; Grigorean, VT; Onose, G; Sandu, AM; Popescu, M; Burnei, G; Strambu, V; Sinescu, C

2010-01-01

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 deep vein thrombosis and long–term risk for coronary heart disease and systemic atherosclerosis are also described. Proper prophylaxis, including non–pharmacologic and pharmacological strategies, diminishes the occurrence of the vascular dysfunction following SCI. Each vascular disturbance requires a specific treatment. PMID:20945818

Changes in Afferent Activity After Spinal Cord Injury

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2010-01-01

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

[Homogeneous spinal-shortening axial decompression procedure for tethered cord syndrome].

PubMed

Wang, Haibo; Sun, Jingchuan; Wang, Yuan; Wu, Zhao; Xu, Tao; Chen, Kefu; Shi, Guodong; Yuan, Wen; Jia, Lianshun; Shi, Jiangang

2015-06-16

Surgical detethering is a traditional treatment for symptomatic tethered cord syndrome. However, such complications as cerebrospinal fluid leakage and neurologic deterioration are common. Homogeneous spinal-shortening axial decompression (HSAD) is a modified procedure of monosegmental spinal-shortening osteotomy and it is a novel surgical alternative of reducing neural tension indirectly. The objective was to evaluate the surgical outcomes of HSAD for tethered cord syndrome. The surgical outcomes were examined for 15 consecutive patients with tethered cord syndrome undergoing HSAD from April 2010 to July 2014. Improvements of neurological symptoms including urinary dysfunction, lower-extremity motor and sensory disturbances and/or gait abnormalities, low-back and/or lower-extremity pain, bowel incontinence and sexual dysfunction were evaluated. Their average follow-up period was 21.5 months. The length of spinal column shortening was 17.2 ± 2.9 mm. Urinary dysfunction (n = 9) was the most common residual deficit. All 9 patients with urological symptoms reported improvements, although deficits persisted at the last follow-up. All patients with lower-extremity motor dysfunction improved and 4 (50.0%) noted complete resolution of preoperative lower-extremity sensory symptoms. All patients reported immediate low-back or lower-extremity pain relief after HSAD. One patient reported improved sexual functioning and regained complete erectile capabilities. Two patients (11%) experienced less satisfactory symptomatic or functional benefit from HSAD. However, the main objective of surgery was to prevent further worsening of neurological status. Complete bone union at osteotomy site was noted in all cases at the last follow-up. As a novel surgical option for tethered cord syndrome, HSAD may avoid such complications as cerebrospinal fluid leakage or neurologic deterioration commonly encountered during traditional detethering surgery. All patients gain satisfactory functional outcomes without complications compared to their preoperative symptoms.

Malignant spinal cord compression in cancer patients may be mimicked by a primary spinal cord tumour.

PubMed

Mohammadianpanah, M; Vasei, M; Mosalaei, A; Omidvari, S; Ahmadloo, N

2006-12-01

Although it is quite rare, second primary neoplasms in cancer patients may present with the signs and symptoms of malignant spinal cord compression. Primary spinal cord tumours in the cancer patients may be deceptive and considered as the recurrent first cancer. Therefore, it should be precisely differentiated and appropriately managed. We report such a case of intramedullary ependymoma of the cervical spinal cord mimicking metatstatic recurrent lymphoma and causing cord compression. A 50-year-old man developed intramedullary ependymoma of the cervical spinal cord 1.5 years following chemoradiation for Waldeyer's ring lymphoma. He presented with a 2-month history of neck pain, progressive upper- and lower-extremity numbness and weakness, and bowel and bladder dysfunction. Magnetic resonance imaging revealed an intramedullary expansive lesion extending from C4 to C6 levels of the cervical spinal cord. The clinical and radiological findings were suggestive of malignant process. A comprehensive investigation failed to detect another site of disease. He underwent operation, and the tumour was subtotally resected. The patient's neurological deficits improved subsequently. The development of the intramedullary ependymoma following treating lymphoma has not been reported. We describe the clinical, radiological and pathological findings of this case and review the literature.

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

PubMed

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

2015-12-07

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

A valuable animal model of spinal cord injury to study motor dysfunctions, comorbid conditions, and aging associated diseases.

PubMed

Rouleau, Pascal; Guertin, Pierre A

2013-01-01

Most animal models of contused, compressed or transected spinal cord injury (SCI) require a laminectomy to be performed. However, despite advantages and disadvantages associated with each of these models, the laminectomy itself is generally associated with significant problems including longer surgery and anaesthesia (related post-operative complications), neuropathic pain, spinal instabilities, deformities, lordosis, and biomechanical problems, etc. This review provides an overview of findings obtained mainly from our laboratory that are associated with the development and characterization of a novel murine model of spinal cord transection that does not require a laminectomy. A number of studies successfully conducted with this model provided strong evidence that it constitutes a simple, reliable and reproducible transection model of complete paraplegia which is particularly useful for studies on large cohorts of wild-type or mutant animals - e.g., drug screening studies in vivo or studies aimed at characterizing neuronal and non-neuronal adaptive changes post-trauma. It is highly suitable also for studies aimed at identifying and developing new pharmacological treatments against aging associated comorbid problems and specific SCI-related dysfunctions (e.g., stereotyped motor behaviours such as locomotion, sexual response, defecation and micturition) largely related with 'command centers' located in lumbosacral areas of the spinal cord.

The control of male sexual responses.

PubMed

Courtois, Frédérique; Carrier, Serge; Charvier, Kathleen; Guertin, Pierre A; Journel, Nicolas Morel

2013-01-01

Male sexual responses are reflexes mediated by the spinal cord and modulated by neural circuitries involving both the peripheral and central nervous system. While the brain interact with the reflexes to allow perception of sexual sensations and to exert excitatory or inhibitory influences, penile reflexes can occur despite complete transections of the spinal cord, as demonstrated by the reviewed animal studies on spinalization and human studies on spinal cord injury. Neurophysiological and neuropharmacological substrates of the male sexual responses will be discussed in this review, starting with the spinal mediation of erection and its underlying mechanism with nitric oxide (NO), followed by the description of the ejaculation process, its neural mediation and its coordination by the spinal generator of ejaculation (SGE), followed by the occurrence of climax as a multisegmental sympathetic reflex discharge. Brain modulation of these reflexes will be discussed through neurophysiological evidence involving structures such as the medial preoptic area of hypothalamus (MPOA), the paraventricular nucleus (PVN), the periaqueductal gray (PAG), and the nucleus para-gigantocellularis (nPGI), and through neuropharmacological evidence involving neurotransmitters such as serotonin (5-HT), dopamine and oxytocin. The pharmacological developments based on these mechanisms to treat male sexual dysfunctions will complete this review, including phosphodiesterase (PDE-5) inhibitors and intracavernous injections (ICI) for the treatment of erectile dysfunctions (ED), selective serotonin reuptake inhibitor (SSRI) for the treatment of premature ejaculation, and cholinesterase inhibitors as well as alpha adrenergic drugs for the treatment of anejaculation and retrograde ejaculation. Evidence from spinal cord injured studies will be highlighted upon each step.

Cardiovascular and temperature changes in spinal cord injured rats at rest and during autonomic dysreflexia

PubMed Central

Laird, A S; Carrive, P; Waite, P M E

2006-01-01

In patients with high spinal cord injuries autonomic dysfunction can be dangerous, leading to medical complications such as postural hypotension, autonomic dysreflexia and temperature disturbance. While animal models have been developed to study autonomic dysreflexia, associated temperature changes have not been documented. Our aim here was to use radiotelemetry and infrared thermography in rodents to record the development of cardiovascular and skin temperature changes following complete T4 transection. In adult male Wistar rats (n = 5), responses were assessed prior to spinal cord injury (intact) and for 6 weeks following injury. Statistical analysis by a repeated-measure ANOVA revealed that following spinal cord injury (SCI), rats exhibited decreased mean arterial pressure (MAP, average decrease of 26 mmHg; P < 0.035) and elevated heart rate (HR, average increase of 65 bpm, P < 0.035) at rest. The basal core body temperature following SCI was also significantly lower than intact levels (−0.9°C; P < 0.0035). Associated with this decreased basal core temperature following SCI was an increased skin temperature of the mid-tail and hindpaw (+5.6 and +4.0°C, respectively; P < 0.0003) consistent with decreased cutaneous vasoconstrictor tone. Autonomic dysreflexia, in response to a 1 min colorectal distension (25 mmHg), was fully developed by 4 weeks after spinal cord transection, producing increases in MAP greater than 25 mmHg (P < 0.0003). In contrast to the tachycardia seen in intact animals in response to colorectal distension, SCI animals exhibited bradycardia (P < 0.0023). During episodes of autonomic dysreflexia mid-tail surface temperature decreased (approx. −1.7°C, P < 0.012), consistent with cutaneous vasoconstriction. This is the first study to compare cardiovascular dysfunction with temperature changes following spinal cord transection in rats. PMID:16973703

Soluble TNFα Signaling within the Spinal Cord Contributes to the Development of Autonomic Dysreflexia and Ensuing Vascular and Immune Dysfunction after Spinal Cord Injury.

PubMed

Mironets, Eugene; Osei-Owusu, Patrick; Bracchi-Ricard, Valerie; Fischer, Roman; Owens, Elizabeth A; Ricard, Jerome; Wu, Di; Saltos, Tatiana; Collyer, Eileen; Hou, Shaoping; Bethea, John R; Tom, Veronica J

2018-04-25

Cardiovascular disease and susceptibility to infection are leading causes of morbidity and mortality for individuals with spinal cord injury (SCI). A major contributor to these is autonomic dysreflexia (AD), an amplified reaction of the autonomic nervous system (hallmarked by severe hypertension) in response to sensory stimuli below the injury. Maladaptive plasticity of the spinal sympathetic reflex circuit below the SCI results in AD intensification over time. Mechanisms underlying this maladaptive plasticity are poorly understood, restricting the identification of treatments. Thus, no preventative treatments are currently available. Neuroinflammation has been implicated in other pathologies associated with hyperexcitable neural circuits. Specifically, the soluble form of TNFα (sTNFα) is known to play a role in neuroplasticity. We hypothesize that persistent expression of sTNFα in spinal cord underlies AD exacerbation. To test this, we intrathecally administered XPro1595, a biologic that renders sTNFα nonfunctional, after complete, high-level SCI in female rats. This dramatically attenuated the intensification of colorectal distension-induced and naturally occurring AD events. This improvement is mediated via decreased sprouting of nociceptive primary afferents and activation of the spinal sympathetic reflex circuit. We also examined peripheral vascular function using ex vivo pressurized arterial preparations and immune function via flow cytometric analysis of splenocytes. Diminishing AD via pharmacological inhibition of sTNFα mitigated ensuing vascular hypersensitivity and immune dysfunction. This is the first demonstration that neuroinflammation-induced sTNFα is critical for altering the spinal sympathetic reflex circuit, elucidating a novel mechanism for AD. Importantly, we identify the first potential pharmacological, prophylactic treatment for this life-threatening syndrome. SIGNIFICANCE STATEMENT Autonomic dysreflexia (AD), a disorder that develops after spinal cord injury (SCI) and is hallmarked by sudden, extreme hypertension, contributes to cardiovascular disease and susceptibility to infection, respectively, two leading causes of mortality and morbidity in SCI patients. We demonstrate that neuroinflammation-induced expression of soluble TNFα plays a critical role in AD, elucidating a novel underlying mechanism. We found that intrathecal administration after SCI of a biologic that inhibits soluble TNFα signaling dramatically attenuates AD and significantly reduces AD-associated peripheral vascular and immune dysfunction. We identified mechanisms behind diminished plasticity of neuronal populations within the spinal sympathetic reflex circuit. This study is the first to pinpoint a potential pharmacological, prophylactic strategy to attenuate AD and ensuing cardiovascular and immune dysfunction. Copyright © 2018 the authors 0270-6474/18/384147-17$15.00/0.

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

PubMed

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

2017-01-01

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

Autonomic Nervous System in Paralympic Athletes with Spinal Cord Injury.

PubMed

Walter, Matthias; Krassioukov, Andrei V

2018-05-01

Individuals sustaining a spinal cord injury (SCI) frequently suffer from sensorimotor and autonomic impairment. Damage to the autonomic nervous system results in cardiovascular, respiratory, bladder, bowel, and sexual dysfunctions, as well as temperature dysregulation. These complications not only impede quality of life, but also affect athletic performance of individuals with SCI. This article summarizes existing evidence on how damage to the spinal cord affects the autonomic nervous system and impacts the performance in athletes with SCI. Also discussed are frequently used performance-enhancing strategies, with a special focus on their legal aspect and implication on the athletes' health. Copyright © 2018 Elsevier Inc. All rights reserved.

Neuromodulation of lower limb motor control in restorative neurology.

PubMed

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

2012-06-01

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

Neuromodulation of lower limb motor control in restorative neurology

PubMed Central

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

2012-01-01

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

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

PubMed Central

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

2016-01-01

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

Automatic 3D segmentation of spinal cord MRI using propagated deformable models

NASA Astrophysics Data System (ADS)

De Leener, B.; Cohen-Adad, J.; Kadoury, S.

2014-03-01

Spinal cord diseases or injuries can cause dysfunction of the sensory and locomotor systems. Segmentation of the spinal cord provides measures of atrophy and allows group analysis of multi-parametric MRI via inter-subject registration to a template. All these measures were shown to improve diagnostic and surgical intervention. We developed a framework to automatically segment the spinal cord on T2-weighted MR images, based on the propagation of a deformable model. The algorithm is divided into three parts: first, an initialization step detects the spinal cord position and orientation by using the elliptical Hough transform on multiple adjacent axial slices to produce an initial tubular mesh. Second, a low-resolution deformable model is iteratively propagated along the spinal cord. To deal with highly variable contrast levels between the spinal cord and the cerebrospinal fluid, the deformation is coupled with a contrast adaptation at each iteration. Third, a refinement process and a global deformation are applied on the low-resolution mesh to provide an accurate segmentation of the spinal cord. Our method was evaluated against a semi-automatic edge-based snake method implemented in ITK-SNAP (with heavy manual adjustment) by computing the 3D Dice coefficient, mean and maximum distance errors. Accuracy and robustness were assessed from 8 healthy subjects. Each subject had two volumes: one at the cervical and one at the thoracolumbar region. Results show a precision of 0.30 +/- 0.05 mm (mean absolute distance error) in the cervical region and 0.27 +/- 0.06 mm in the thoracolumbar region. The 3D Dice coefficient was of 0.93 for both regions.

Cell therapy for spinal cord injury informed by electromagnetic waves.

PubMed

Finnegan, Jack; Ye, Hui

2016-10-01

Spinal cord injury devastates the CNS, besetting patients with symptoms including but not limited to: paralysis, autonomic nervous dysfunction, pain disorders and depression. Despite the identification of several molecular and genetic factors, a reliable regenerative therapy has yet to be produced for this terminal disease. Perhaps the missing piece of this puzzle will be discovered within endogenous electrotactic cellular behaviors. Neurons and stem cells both show mediated responses (growth rate, migration, differentiation) to electromagnetic waves, including direct current electric fields. This review analyzes the pathophysiology of spinal cord injury, the rationale for regenerative cell therapy and the evidence for directing cell therapy via electromagnetic waves shown by in vitro experiments.

Brainstem dysfunction protects against syncope in multiple sclerosis.

PubMed

Habek, Mario; Krbot Skorić, Magdalena; Crnošija, Luka; Adamec, Ivan

2015-10-15

The aim of this study was to investigate the correlation between autonomic dysfunction in multiple sclerosis (MS) and brainstem dysfunction evaluated with the vestibular evoked myogenic potentials (VEMP) score and conventional MRI. Forty-five patients with the diagnosis of clinically isolated syndrome (CIS) suggestive of MS were enrolled. VEMP, heart rate, and blood pressure responses to the Valsalva maneuver, heart rate response to deep breathing, and pain provoked head-up tilt table test, as well as brain and spinal cord MRI were performed. There was no difference in the VEMP score between patients with and without signs of sympathetic or parasympathetic dysfunction. However, patients with syncope had significantly lower VEMP score compared to patients without syncope (p<0.01). Patients with orthostatic hypotension (OH) showed a trend of higher VEMP score compared to patients without OH (p=0.06). There was no difference in the presence of lesions in the brainstem or cervical spinal cord between patients with or without any of the studied autonomic parameters. The model consisting of a VEMP score of ≤5 and normal MRI of the midbrain and cervical spinal cord has sensitivity and specificity of 83% for the possibility that the patient with MS can develop syncope. Pathophysiological mechanisms underlying functional and structural disorders of autonomic nervous system in MS differ significantly. While preserved brainstem function is needed for development of syncope, structural disorders like OH could be associated with brainstem dysfunction. Copyright © 2015 Elsevier B.V. All rights reserved.

Dendritic spine dysgenesis contributes to hyperreflexia after spinal cord injury

PubMed Central

Bandaru, Samira P.; Liu, Shujun; Waxman, Stephen G.

2014-01-01

Hyperreflexia and spasticity are chronic complications in spinal cord injury (SCI), with limited options for safe and effective treatment. A central mechanism in spasticity is hyperexcitability of the spinal stretch reflex, which presents symptomatically as a velocity-dependent increase in tonic stretch reflexes and exaggerated tendon jerks. In this study we tested the hypothesis that dendritic spine remodeling within motor reflex pathways in the spinal cord contributes to H-reflex dysfunction indicative of spasticity after contusion SCI. Six weeks after SCI in adult Sprague-Dawley rats, we observed changes in dendritic spine morphology on α-motor neurons below the level of injury, including increased density, altered spine shape, and redistribution along dendritic branches. These abnormal spine morphologies accompanied the loss of H-reflex rate-dependent depression (RDD) and increased ratio of H-reflex to M-wave responses (H/M ratio). Above the level of injury, spine density decreased compared with below-injury spine profiles and spine distributions were similar to those for uninjured controls. As expected, there was no H-reflex hyperexcitability above the level of injury in forelimb H-reflex testing. Treatment with NSC23766, a Rac1-specific inhibitor, decreased the presence of abnormal dendritic spine profiles below the level of injury, restored RDD of the H-reflex, and decreased H/M ratios in SCI animals. These findings provide evidence for a novel mechanistic relationship between abnormal dendritic spine remodeling in the spinal cord motor system and reflex dysfunction in SCI. PMID:25505110

Effect of spinal anterior root stimulation and sacral deafferentation on bladder and sexual dysfunction in spinal cord injury.

PubMed

Zaer, Hamed; Rasmussen, Mikkel Mylius; Zepke, Franko; Bodin, Charlotte; Domurath, Burkhard; Kutzenberger, Johannes

2018-05-10

Spinal cord injury (SCI) is a highly devastating injury with a variety of complications; among them are neurogenic bladder, bowel, and sexual dysfunction. We aimed to evaluate the effect of sacral anterior root stimulation with sacral deafferentation (SARS-SDAF) on neurogenic bladder and sexual dysfunction in a large well-defined spinal cord injury cohort. In the manner of cross-sectional study, subjects undergone SARS-SDAF between September 1986 and July 2011 answered a questionnaire concerning conditions before and after surgery in the department of Neuro-Urology, Bad Wildungen, Germany. In total 287 of 587 subjects were analyzed. Median age was 49 years (range 19-80), median time from SCI to surgery was 10 years (range 0-49), and from surgery to follow-up 13 years (range 1-25). Of the analyzed subjects, 100% of both gender used SARS for bladder emptying. On the visual analogue scale (VAS) ranging from 0 to 10 (best), satisfaction with SARS-SDAF was 10 concerning bladder emptying, however 5 and 8 regarding sexual performance, for female and male users, respectively. Baseline and follow-up comparison showed a decline in self-intermittent catheterization (p < 0.0001), partial catheterization by attendant (p = 0.0125), complete catheterization and suprapubic catheterization (p < 0.0001), transurethral catheterization (p < 0.0011), and fewer cases of involuntary urine leakage (p < 0.0001). The SARS-SDAF is a beneficial multi-potential treatment method with simultaneous positive effect on multi-organ dysfunction among SCI subjects.

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

PubMed

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

2014-11-01

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

Design and testing of a controlled electromagnetic spinal cord impactor for use in large animal models of acute traumatic spinal cord injury.

PubMed

Petteys, Rory J; Spitz, Steven M; Syed, Hasan; Rice, R Andrew; Sarabia-Estrada, Rachel; Goodwin, C Rory; Sciubba, Daniel M; Freedman, Brett A

2017-09-01

Spinal cord injury (SCI) causes debilitating neurological dysfunction and has been observed in warfighters injured in IED blasts. Clinical benefit of SCI treatment remains elusive and better large animal models are needed to assess treatment options. Here, we describe a controlled electromagnetic spinal cord impactor for use in large animal models of SCI. A custom spinal cord impactor and platform were fabricated for large animals (e.g., pig, sheep, dog, etc.). Impacts were generated by a voice coil actuator; force and displacement were measured with a load cell and potentiometer respectively. Labview (National Instruments, Austin, TX) software was used to control the impact cycle and import force and displacement data. Software finite impulse response (FIR) filtering was employed for all input data. Silicon tubing was used a surrogate for spinal cord in order to test the device; repeated impacts were performed at 15, 25, and 40 Newtons. Repeated impacts demonstrated predictable results at each target force. The average duration of impact was 71.2 ±6.1ms. At a target force of 40N, the output force was 41.5 ±0.7N. With a target of 25N, the output force was 23.5 ±0.6N; a target of 15Newtons revealed an output force of 15.2 ±1.4N. The calculated acceleration range was 12.5-21.2m/s 2 . This custom spinal cord impactor reliably delivers precise impacts to the spinal cord and will be utilized in future research to study acute traumatic SCI in a large animal. Published by Elsevier Ltd.

Spinal dural arteriovenous fistulas: the most frequent vascular malformations of the spinal cord.

PubMed

Iglesias Gordo, J; Martínez García, R

Spinal dural arteriovenous fistulas are produced by direct communication between the arterial and venous systems of the spinal cord, causing hypertension in the latter with spinal cord dysfunction. It is a rare pathology with unknown etiology and non-specific clinical symptoms that usually results in a delayed diagnosis. Often radiologists are the first to guide the disease towards an adequate diagnosis. Characteristic findings can be seen through MR or MR angiography, and may even locate the fistula in a high percentage of cases, although the pathology must be confirmed by spinal angiography. There are two treatment modalities: endovascular and surgical therapy. Endovascular treatment has improved in recent years with the advantages of a less invasive approach and is therefore usually chosen as primary therapy. In this article we review the main clinical manifestations, imaging findings and treatment of this pathology. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Use of Optical Mapping to Evaluate Mechanisms and New Therapies for Bladder Dysfunction Due to Spinal Cord Injury

DTIC Science & Technology

2013-10-01

TERMS Lower urinary tract symptoms (LUTS), spinal cord injury (SCI), Botulinum Toxin Type A and β3 adrenoceptor agonists 16. SECURITY...focused on the therapeutic benefits of β3 adrenoceptor agonists, botulinum neurotoxin type A (BTX-A) intradetrusor injections and their combination...compromised by the toxin . Thus, β3 adrenoceptor agonists in combination with BTX-A are beneficial in improving bladder function in SCI patients. 15. SUBJECT

Psychological impact and sexual dysfunction in men with and without spinal cord injury.

PubMed

Cobo Cuenca, Ana I; Sampietro-Crespo, Antonio; Virseda-Chamorro, Miguel; Martín-Espinosa, Noelia

2015-02-01

The World Health Organization recognizes sexual health as a fundamental right that should be guaranteed to all individuals. Sexual dysfunction affects various aspects in the lives (physical, psychic, and social) of affected persons. To assess the different types of sexual dysfunction, the quality of life (QOL), depression, anxiety, and levels of self-esteem observed in 165 men with sexual dysfunction, both with and without spinal cord injury (SCI). Case control study of 85 men with SCI and sexual dysfunction, and 80 men without SCI that have sexual dysfunction. The Sexual Health Evaluation Scale, the Fugl-Meyer Life Satisfaction Questionnaire scale, the Hospital Anxiety and Depression Scale, the Evaluation of the Sexual Health Scale, and Rosenberg's Self-esteem Scale were all used for data collection. Of the members in group A (with SCI), 89.4% (76) showed erectile dysfunction, and 75.2% (64) reported anejaculation. In group B (without SCI), 75 (96.8%) showed erectile dysfunction, and 58.7% (47) had disorders of sexual desire. In group A, 16.47 % (14) showed signs of depression, and 35.3% (30) had signs of anxiety. In group B, 30% (24) had elevated scores regarding depression, and 48.75% (39) had high scores for anxiety. All of the participants reported a high general QOL and a high satisfaction with their QOL but reported that their satisfaction with their sexual lives was only at the acceptable level. Social QOL is significantly higher in the SCI group (t Student P=0.031). The QOL, self-esteem, and anxiety and depression levels are significantly correlated. Men with sexual dysfunction strive to adapt to their situations, with the relationship between the type of sexual dysfunction and the QOL, mood (depression), and self-esteem all being important considerations. Sexuality and employment status are the areas where men with spinal cord injuries report less satisfaction. © 2014 International Society for Sexual Medicine.

Neurogenic bladder in spinal cord injury patients

PubMed Central

Taweel, Waleed Al; Seyam, Raouf

2015-01-01

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

Male sexual dysfunction and infertility associated with neurological disorders

PubMed Central

Fode, Mikkel; Krogh-Jespersen, Sheila; Brackett, Nancy L; Ohl, Dana A; Lynne, Charles M; Sønksen, Jens

2012-01-01

Normal sexual and reproductive functions depend largely on neurological mechanisms. Neurological defects in men can cause infertility through erectile dysfunction, ejaculatory dysfunction and semen abnormalities. Among the major conditions contributing to these symptoms are pelvic and retroperitoneal surgery, diabetes, congenital spinal abnormalities, multiple sclerosis and spinal cord injury. Erectile dysfunction can be managed by an increasingly invasive range of treatments including medications, injection therapy and the surgical insertion of a penile implant. Retrograde ejaculation is managed by medications to reverse the condition in mild cases and in bladder harvest of semen after ejaculation in more severe cases. Anejaculation might also be managed by medication in mild cases while assisted ejaculatory techniques including penile vibratory stimulation and electroejaculation are used in more severe cases. If these measures fail, surgical sperm retrieval can be attempted. Ejaculation with penile vibratory stimulation can be done by some spinal cord injured men and their partners at home, followed by in-home insemination if circumstances and sperm quality are adequate. The other options always require assisted reproductive techniques including intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection. The method of choice depends largely on the number of motile sperm in the ejaculate. PMID:22138899

The Prevalence and Phenotype of Activated Microglia/Macrophages within the Spinal Cord of the Hyperostotic Mouse (twy/twy) Changes in Response to Chronic Progressive Spinal Cord Compression: Implications for Human Cervical Compressive Myelopathy

PubMed Central

Hirai, Takayuki; Uchida, Kenzo; Nakajima, Hideaki; Guerrero, Alexander Rodriguez; Takeura, Naoto; Watanabe, Shuji; Sugita, Daisuke; Yoshida, Ai; Johnson, William E. B.; Baba, Hisatoshi

2013-01-01

Background Cervical compressive myelopathy, e.g. due to spondylosis or ossification of the posterior longitudinal ligament is a common cause of spinal cord dysfunction. Although human pathological studies have reported neuronal loss and demyelination in the chronically compressed spinal cord, little is known about the mechanisms involved. In particular, the neuroinflammatory processes that are thought to underlie the condition are poorly understood. The present study assessed the localized prevalence of activated M1 and M2 microglia/macrophages in twy/twy mice that develop spontaneous cervical spinal cord compression, as a model of human disease. Methods Inflammatory cells and cytokines were assessed in compressed lesions of the spinal cords in 12-, 18- and 24-weeks old twy/twy mice by immunohistochemical, immunoblot and flow cytometric analysis. Computed tomography and standard histology confirmed a progressive spinal cord compression through the spontaneously development of an impinging calcified mass. Results The prevalence of CD11b-positive cells, in the compressed spinal cord increased over time with a concurrent decrease in neurons. The CD11b-positive cell population was initially formed of arginase-1- and CD206-positive M2 microglia/macrophages, which later shifted towards iNOS- and CD16/32-positive M1 microglia/macrophages. There was a transient increase in levels of T helper 2 (Th2) cytokines at 18 weeks, whereas levels of Th1 cytokines as well as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and macrophage antigen (Mac) −2 progressively increased. Conclusions Spinal cord compression was associated with a temporal M2 microglia/macrophage response, which may act as a possible repair or neuroprotective mechanism. However, the persistence of the neural insult also associated with persistent expression of Th1 cytokines and increased prevalence of activated M1 microglia/macrophages, which may lead to neuronal loss and demyelination despite the presence of neurotrophic factors. This understanding of the aetiopathology of chronic spinal cord compression is of importance in the development of new treatment targets in human disease. PMID:23717624

[Acute non-traumatic myelopathy in children and adolescents].

PubMed

Arroyo, Hugo A

2013-09-06

The term 'acute myelopathies'--referred to a spinal cord dysfunction--represent a heterogeneous group of disorders with distinct etiologies, clinical and radiologic features, and prognoses. The objective of this review is to discuss the non-traumatic acute myelopathies. Acute myelopathy can be due to several causes as infective agents or inflammatory processes, such as in acute myelitis, compressive lesions, vascular lesions, etc. The clinical presentation is often dramatic with tetraparesis or paraparesis, sensory disturbances and bladder and/or bowel dysfunction. History and physical examination are used to localize the lesion to the root or specific level of the cord, which can guide imaging. Different syndromes are recognized: complete transverse lesion, central grey matter syndrome, anterior horn syndrome, anterior spinal artery syndrome, etc). The first priority is to rule out a compressive lesion. If a myelopathy is suspected, a gadolinium-enhanced MRI of the spinal cord should be obtained as soon as possible. If there is no structural lesion such as epidural blood or a spinal mass, then the presence or absence of spinal cord inflammation should be documented with a lumbar puncture. The absence of pleocytosis would lead to consideration of non inflammatory causes of myelopathy such as arteriovenous malformations, fibrocartilaginous embolism, or possibly early inflammatory myelopathy. In the presence of an inflammatory process (defined by gadolinium enhancement, cerebrospinal fluid pleocytosis, or elevated cerebrospinal fluid immunoglobulin index), one should determine whether there is an inflammatory or an infectious cause. Different virus, bacterias, parasites and fungi have to be considered as autoimmune and inflammatory diseases that involve the central nervous system.

Aging among the Disabled: A Neglected Area.

ERIC Educational Resources Information Center

Kemp, Bryan

The paper addresses issues involved in the aging of persons disabled earlier through spinal dysfunction (post-polio and spinal cord injury) and mental retardation. Biological, psychological, and social aspects of aging are examined separately. In a discussion of longevity and physical health, causes of functional aging are considered.…

Review of the History of Non-traumatic Spinal Cord Dysfunction.

PubMed

New, Peter Wayne; Biering-Sørensen, Fin

2017-01-01

Background: The incidence of non-traumatic spinal cord dysfunction (SCDys) is reported to be higher than traumatic spinal cord injury (SCI) in many countries. No formal review of the history of SCDys has been published. Objective: This article aims to identify key highlights in the history of SCDys. Method: An electronic literature search was conducted (January 2017) using MEDLINE (1946-2016) and Embase (1974-2016) databases for publications regarding the history of SCDys. Publications on the history of SCI and a selection of neurology textbooks and books on the history of neurology were reviewed for potentially relevant references. The focus of the literature search was on identifying publications that detail key highlights regarding the history of the diagnosis and management of the most common SCDys conditions, as well as those of historical significance. Results: The electronic search of MEDLINE and Embase identified 11 relevant publications. The majority of publications included were identified from the authors' libraries and a selection of books on neurology and the history of neurology. Conclusions: This review outlines the history of SCDys, taking a broader historical perspective and covering the increasing awareness of the role of the spinal cord and knowledge of neuroanatomy. Key milestones in the history of the diagnosis and management of the most common SCDys conditions are presented. An appreciation of the history of SCDys increases our understanding of the large number of people who contributed to our current knowledge of these conditions and in some situations helps guide efforts regarding prevention of SCDys.

Inflatable artificial sphincter - series (image)

MedlinePlus

... sphincter dysfunction related to spinal cord injury or multiple sclerosis. Most experts advise their patients to try medication and bladder retraining therapy first before resorting to this treatment. Alternatives to ...

Degenerative Cervical Myelopathy: A Spectrum of Related Disorders Affecting the Aging Spine.

PubMed

Tetreault, Lindsay; Goldstein, Christina L; Arnold, Paul; Harrop, James; Hilibrand, Alan; Nouri, Aria; Fehlings, Michael G

2015-10-01

Cervical spinal cord dysfunction can result from either traumatic or nontraumatic causes, including tumors, infections, and degenerative changes. In this article, we review the range of degenerative spinal disorders resulting in progressive cervical spinal cord compression and propose the adoption of a new term, degenerative cervical myelopathy (DCM). DCM comprises both osteoarthritic changes to the spine, including spondylosis, disk herniation, and facet arthropathy (collectively referred to as cervical spondylotic myelopathy), and ligamentous aberrations such as ossification of the posterior longitudinal ligament and hypertrophy of the ligamentum flavum. This review summarizes current knowledge of the pathophysiology of DCM and describes the cascade of events that occur after compression of the spinal cord, including ischemia, destruction of the blood-spinal cord barrier, demyelination, and neuronal apoptosis. Important features of the diagnosis of DCM are discussed in detail, and relevant clinical and imaging findings are highlighted. Furthermore, this review outlines valuable assessment tools for evaluating functional status and quality of life in these patients and summarizes the advantages and disadvantages of each. Other topics of this review include epidemiology, the prevalence of degenerative changes in the asymptomatic population, the natural history and rates of progression, risk factors of diagnosis (clinical, imaging and genetic), and management strategies.

Neuroanatomy, neurophysiology, and dysfunction of the female lower urinary tract: a review.

PubMed

Unger, Cécile A; Tunitsky-Bitton, Elena; Muffly, Tyler; Barber, Matthew D

2014-01-01

The 2 major functions of the lower urinary tract are the storage and emptying of urine. These processes are controlled by complex neurophysiologic mechanisms and are subject to injury and disease. When there is disruption of the neurologic control centers, dysfunction of the lower urinary tract may occur. This is sometimes referred to as the "neurogenic bladder." The manifestation of dysfunction depends on the level of injury and severity of disruption. Patients with lesions above the spinal cord often have detrusor overactivity with no disruption in detrusor-sphincter coordination. Patients with well-defined suprasacral spinal cord injuries usually present with intact reflex detrusor activity but have detrusor sphincter dyssynergia, whereas injuries to or below the sacral spinal cord usually lead to persistent detrusor areflexia. A complete gynecologic, urologic, and neurologic examination should be performed when evaluating patients with neurologic lower urinary tract dysfunction. In addition, urodynamic studies and neurophysiologic testing can be used in certain circumstances to help establish diagnosis or to achieve better understanding of a patient's vesicourethral functioning. In the management of neurogenic lower urinary tract dysfunction, the primary goal is improvement of a patient's quality of life. Second to this is the prevention of chronic damage to the bladder and kidneys, which can lead to worsening impairment and symptoms. Treatment is often multifactorial, including behavioral modifications, bladder training programs, and pharmacotherapy. Surgical procedures are often a last resort option for management. An understanding of the basic neurophysiologic mechanisms of the lower urinary tract can guide providers in their evaluation and treatment of patients who present with lower urinary tract disorders. As neurologic diseases progress, voiding function often changes or worsens, necessitating a good understanding of the underlying physiology in question.

Dysfunctional oligodendrocyte progenitor cell (OPC) populations may inhibit repopulation of OPC depleted tissue.

PubMed

Chari, D M; Huang, W L; Blakemore, W F

2003-09-15

We have attempted to extend a previously described rat model of focal oligodendrocyte progenitor cell (OPC) depletion, using 40 Gy X-irradiation (Chari and Blakemore [2002] Glia 37:307-313), to the adult mouse spinal cord, to examine the ability of OPCs present in adjacent normal areas to colonise areas of progenitor depletion. In contrast to rat, OPCs in the mouse spinal cord appeared to be a comparatively radiation-resistant population, as 30-35% of OPCs survived in X-irradiated tissue (whereas <1% of OPCs survive in X-irradiated rat spinal cord). The numbers of surviving OPCs remained constant with time indicating that this population was incapable of regenerating itself in response to OPC loss. Additionally, these OPCs did not contribute to remyelination of axons when demyelinating lesions were placed in X-irradiated tissue, suggesting that the surviving cells are functionally impaired. Importantly, the length of the OPC-depleted area did not diminish with time, as would be expected if progressive repopulation of OPC-depleted areas by OPCs from normal areas was occurring. Our findings therefore raise the possibility that the presence of a residual dysfunctional OPC population may inhibit colonisation of such areas by normal OPCs. Copyright 2003 Wiley-Liss, Inc.

Neurogenic detrusor overactivity in patients with spinal cord injury: evaluation and management.

PubMed

Sahai, Arun; Cortes, Eduardo; Seth, Jai; Khan, Muhammad Shamim; Panicker, Jalesh; Kelleher, Cornelius; Kessler, Thomas M; Fowler, Clare J; Dasgupta, Prokar

2011-12-01

Lower urinary tract dysfunction can have a significant impact on patients with spinal cord injury. Over the years, many treatment options have become available. This article reviews the assessment and management of neurogenic detrusor overactivity, with a particular focus on articles from the recent literature. Recent guidelines on the subject will be discussed. Management options include antimuscarinics and bladder emptying measures, botulinum toxin A, and neuromodulation in refractory cases and surgery for intractable cases. Recent and relevant publications in these areas will be summarized and discussed.

Symptomatic arrhythmias due to syringomyelia-induced severe autonomic dysfunction.

PubMed

Riedlbauchová, Lucie; Nedělka, Tomáš; Schlenker, Jakub

2014-10-01

Syringomyelia is characterized by cavity formation in the spinal cord, most often at C2-Th9 level. Clinical manifestation reflects extent and localization of the spinal cord injury. 20-year old woman was admitted for recurrent rest-related presyncopes with sudden manifestation. Paroxysms of sinus bradycardia with SA and AV blocks were repeatedly documented during symptoms. There was normal echocardiographic finding, (para) infectious etiology was not proved. Character of the ECG findings raised suspicion on neurogenic cause. Autonomic nervous system testing demonstrated abnormalities reflecting predominant sympathetic dysfunction. Suspicion on incipient myelopathy was subsequently confirmed by MRI, which discovered syringomyelia at Th5 level as the only pathology. A 52-year old man with hypotrophic quadruparesis resulting from perinatal brain injury was sent for 2-years lasting symptoms (sudden palpitation, sweating, muscle tightness, shaking) with progressive worsening. Symptoms occurred in association with sudden increase of sinus rhythm rate and blood pressure that were provoked by minimal physical activity. Presence of significant autonomic dysregulation with baroreflex hyperreactivity in orthostatic test and symptomatic postural orthostatic tachycardia with verticalization-associated hypertension were proved. MRI revealed syringomyelia at C7 and Th7 level affecting sympathetic centers at these levels. Sympathetic fibers dysfunction at C-Th spinal level may cause significant autonomic dysfunction with arrhythmic manifestation.

Prediction of autonomic dysreflexia during urodynamics: a prospective cohort study.

PubMed

Walter, Matthias; Knüpfer, Stephanie C; Cragg, Jacquelyn J; Leitner, Lorenz; Schneider, Marc P; Mehnert, Ulrich; Krassioukov, Andrei V; Schubert, Martin; Curt, Armin; Kessler, Thomas M

2018-04-13

Autonomic dysreflexia is a severe and potentially life-threatening condition in patients with spinal cord injury, as it can lead to myocardial ischemia, brain hemorrhage, or even death. Urodynamic investigation is the gold standard to assess neurogenic lower urinary tract dysfunction due to spinal cord injury and reveal crucial pathological findings, such as neurogenic detrusor overactivity. However, neurogenic detrusor overactivity and urodynamic investigation are known to be leading triggers of autonomic dysreflexia. Therefore, we aimed to determine predictors of autonomic dysreflexia in individuals with spinal cord injury during urodynamic investigation. This prospective cohort study included 300 patients with spinal cord injuries and complete datasets of continuous non-invasive cardiovascular monitoring, recorded during same session repeat urodynamic investigation. We used logistic regression to reveal predictors of autonomic dysreflexia during urodynamic investigation. We found that level of injury and presence of neurogenic detrusor overactivity were the only two independent significant predictors for autonomic dysreflexia during urodynamic investigation. A lesion at spinal segment T6 or above (odds ratio (OR) 5.5, 95% CI 3.2-9.4) compared to one at T7 or below, and presence of neurogenic detrusor overactivity (OR 2.7, 95% confidence interval (CI) 1.4-4.9) were associated with a significant increased odds of autonomic dysreflexia during urodynamic investigation. Both odds persisted after adjustment for age, sex, and completeness and stage of injury (adjusted OR (AOR) 6.6, 95% CI 3.8-11.7, and AOR 2.2, 95% CI 1.1-4.5, respectively). Further stratification by lesion level showed level-dependent significantly increased adjusted odds of autonomic dysreflexia, i.e., from C1-C4 (AOR 16.2, 95% CI 5.9-57.9) to T4-T6 (AOR 2.6, 95% CI 1.3-5.2), compared to lesions at T7 or below. In patients with neurogenic lower urinary tract dysfunction due to spinal cord injury, autonomic dysreflexia is independently predicted by lesion level and presence of neurogenic detrusor overactivity. Considering the health risks associated with autonomic dysreflexia, such as seizures, stroke, retinal bleeding, or even death, we recommend both continuous cardiovascular monitoring during urodynamic investigation in all spinal cord-injured patients with emphasis on those with cervical lesions, and appropriate neurogenic detrusor overactivity treatment to reduce the probability of potentially life-threatening complications. ClinicalTrials.gov, NCT01293110 .

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

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2013-01-01

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

Inflammatory cascades mediate synapse elimination in spinal cord compression

PubMed Central

2014-01-01

Background Cervical compressive myelopathy (CCM) is caused by chronic spinal cord compression due to spondylosis, a degenerative disc disease, and ossification of the ligaments. Tip-toe walking Yoshimura (twy) mice are reported to be an ideal animal model for CCM-related neuronal dysfunction, because they develop spontaneous spinal cord compression without any artificial manipulation. Previous histological studies showed that neurons are lost due to apoptosis in CCM, but the mechanism underlying this neurodegeneration was not fully elucidated. The purpose of this study was to investigate the pathophysiology of CCM by evaluating the global gene expression of the compressed spinal cord and comparing the transcriptome analysis with the physical and histological findings in twy mice. Methods Twenty-week-old twy mice were divided into two groups according to the magnetic resonance imaging (MRI) findings: a severe compression (S) group and a mild compression (M) group. The transcriptome was analyzed by microarray and RT-PCR. The cellular pathophysiology was examined by immunohistological analysis and immuno-electron microscopy. Motor function was assessed by Rotarod treadmill latency and stride-length tests. Results Severe cervical calcification caused spinal canal stenosis and low functional capacity in twy mice. The microarray analysis revealed 215 genes that showed significantly different expression levels between the S and the M groups. Pathway analysis revealed that genes expressed at higher levels in the S group were enriched for terms related to the regulation of inflammation in the compressed spinal cord. M1 macrophage-dominant inflammation was present in the S group, and cysteine-rich protein 61 (Cyr61), an inducer of M1 macrophages, was markedly upregulated in these spinal cords. Furthermore, C1q, which initiates the classical complement cascade, was more upregulated in the S group than in the M group. The confocal and electron microscopy observations indicated that classically activated microglia/macrophages had migrated to the compressed spinal cord and eliminated synaptic terminals. Conclusions We revealed the detailed pathophysiology of the inflammatory response in an animal model of chronic spinal cord compression. Our findings suggest that complement-mediated synapse elimination is a central mechanism underlying the neurodegeneration in CCM. PMID:24589419

Behavioral Intervention, Exercise, and Nutrition Education to Improve Health and Fitness (BENEfit) in Adolescents With Mobility Impairment Due to Spinal Cord Dysfunction

PubMed Central

Liusuwan, Rungsinee Amanda; Widman, Lana M; Abresch, Richard Ted; Johnson, Allan J; McDonald, Craig M

2007-01-01

Background/Objective: Determine the effects of a nutrition education and exercise intervention on the health and fitness of adolescents with mobility impairment due to spinal cord dysfunction from myelomeningocele and spinal cord injury. Subjects participated in a 16-week intervention consisting of a behavioral approach to lifestyle change, exercise, and nutrition education to improve fitness (BENEfit) program. Participants were given a schedule of aerobic and strengthening exercises and attended nutrition education and behavior modification sessions every other week along with their parent(s). Subjects: Twenty adolescents (aged 11–18 years, mean 15.4 ± 2.2 years) with spinal cord dysfunction. Methods: Subjects were tested immediately prior to starting and upon completion of the program. Aerobic fitness was measured using a ramp protocol with an arm ergometer. Heart rate and oxygen uptake were measured. Values at anaerobic threshold and maximum oxygen uptake were recorded. Peak isokinetic arm and shoulder strength were determined with a dynamometer. Body composition was estimated with dual-energy x-ray absorptiometry. Serum chemistry included measures of cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides. Results: Fourteen individuals completed all testing sessions. There was no significant overall change in weight, body mass index, body mass index z-scores, or serum chemistry. Overall, there was a significant increase in whole body lean tissue without a concomitant increase in whole body fat. Fitness measures revealed a significant increase in maximum power output, work efficiency as measured by the amount of power output produced aerobically, and resting oxygen uptake. Strength measurements revealed a significant increase in shoulder extension strength and a trend towards increased shoulder flexion strength. There were no significant changes in high-density lipoprotein, low-density lipoprotein, total cholesterol, or triglycerides. Conclusions: The BENEfit program shows promise as a method for improving the health and fitness of adolescents with mobility impairments who are at high risk for obesity and obesity-related health conditions. PMID:17874697

Assessment of neurogenic bowel dysfunction impact after spinal cord injury using the International Classification of Functioning, Disability and Health.

PubMed

Pires, Jennifer M; Ferreira, Ana M; Rocha, Filipa; Andrade, Luis G; Campos, Inês; Margalho, Paulo; Laíns, Jorge

2018-05-09

Bowel function is frequently compromised after spinal cord injury (SCI). Regardless of this crucial importance in patients' lives, there is still scarce literature on the Neurogenic Bowel Dysfunction (NBD) deleterious impact on SCI patient's lives and only few studies correlating NBD severity with quality of life (QoL). To our knowledge there are no studies assessing the impact of NBD on the context of ICF domains. To assess NBD after SCI using ICF domains and to assess its impact in QoL. Retrospective data analysis and cross-sectional phone survey. Outpatient spinal cord injury setting. Portuguese adult spinal cord injury patients. Retrospective analysis of demographic data, lesion characteristics and bowel management methods at last inpatient discharge. Cross-sectional phone survey assessing current bowel management methods, the Neurogenic Bowel Dysfunction Score and a Likert scale questionnaire about the impact on ICF domains and QoL. 64 patients answered the questionnaire. The majority was male (65.6%), mean age 56.6±15.6 years, AIS A lesion (39.1%), with a traumatic cause (71.9%). The main bowel management methods were contact laxatives, suppositories and osmotic laxatives. 50.1% of patients scored moderate or severe NBD. Considering ICF domains, the greatest impact was in personal and environmental factors, with 39.1% reporting impact in financial costs, 45.3% in need of assistance, 45.3% in emotional health and 46.9% in loss of privacy. There was a significant association between severity of NBD and negative impact on QoL (p<0.05). The study confirms the major impact of NBD on personal and environmental factors of ICF and on the quality of life of SCI population. These findings confirm that it is relevant to identify the main ICF domains affected by NBD after SCI in order to address targeted interventions, working toward changes in health policies and psychosocial aspects.

Factors associated with sexual functioning in women following spinal cord injury.

PubMed

Harrison, J; Glass, C A; Owens, R G; Soni, B M

1995-12-01

Research into sexuality following spinal cord injury (SCI) has tended to concentrate on male experiences and the physical capabilities for sexual intercourse. The sexuality of women following SCI has only recently been addressed and studies are limited to small numbers and the use of non-standardised measures. The present investigation utilised standard measures of affective state and body satisfaction together with pre and post-injury questionnaire information of sexual dysfunction, feelings about sex and importance of sexual activity in a group of 85 women with SCI. Sexual dysfunction increased significantly post-injury, whilst feelings about sex and it's importance were unaffected. Sexual dysfunction and the importance of sex were inversely correlated. General and Head satisfaction estimates were not significantly different to control samples, whilst Body Satisfaction was increased for women with disabilities. None of the body satisfaction measures were related to the sexual functioning measure. General dissatisfaction was associated depression. Both anxiety and depression were experienced by the same individuals, and anxiety related to current sexual dysfunction. Qualitative data supported previous findings concerning the effects of social and attitudinal barriers on sexual functioning.

Sudden death and paroxysmal autonomic dysfunction in stiff-man syndrome.

PubMed

Mitsumoto, H; Schwartzman, M J; Estes, M L; Chou, S M; La Franchise, E F; De Camilli, P; Solimena, M

1991-04-01

Two women with typical stiff-man syndrome (SMS) developed increasingly frequent attacks of muscle spasms with severe paroxysmal autonomic dysfunctions such as transient hyperpyrexia, diaphoresis, tachypnea, tachycardia, pupillary dilation, and arterial hypertension. Autoantibodies to GABA-ergic neurons were identified in the serum of both patients and in the cerebrospinal fluid of one. Both died suddenly and unexpectedly. General autopsy did not reveal the cause of death. Neuropathological studies revealed perivascular gliosis in the spinal cord and brain stem of one patient and lymphocytic perivascular infiltration in the spinal cord, brain stem, and basal ganglia of the other. The occurrence of a chronic inflammatory reaction in one of the two patients supports the idea that an autoimmune disease against GABA-ergic neurons may be involved in SMS. A review of the literature indicates that functional impairment in SMS is severe and prognosis is unpredictable because of the potential for sudden and unexpected death. Both muscular abnormalities and autonomic dysfunctions may result from autoimmunity directed against GABA-ergic neurons.

QUAD fever: beware of non-infectious fever in high spinal cord injuries.

PubMed

Goyal, Jyoti; Jha, Rakesh; Bhatia, Paramjeet; Mani, Raj Kumar

2017-06-18

A case of cervical spinal cord injury and quadriparesis with prolonged fever is being described. Initially, the patient received treatment for well-documented catheter-related bloodstream infection. High spiking fever returned and persisted with no obvious evidence of infection. The usual non-infectious causes too were carefully excluded. QUAD fever or fever due to spinal cord injury itself was considered. The pathogenetic basis of QUAD fever is unclear but could be attributed to autonomic dysfunction and temperature dysregulation. Awareness of this little known condition could help in avoiding unnecessary antimicrobial therapy and in more accurate prognostication. Unlike several previous reported cases that ended fatally, the present case ran a relatively benign course. The spectrum of presentations may therefore be broader than hitherto appreciated. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Increased excitability of spinal pain reflexes and altered frequency-dependent modulation in the dopamine D3-receptor knockout mouse.

PubMed

Keeler, Benjamin E; Baran, Christine A; Brewer, Kori L; Clemens, Stefan

2012-12-01

Frequency-dependent modulation and dopamine (DA) receptors strongly modulate neural circuits in the spinal cord. Of the five known DA receptor subtypes, the D3 receptor has the highest affinity to DA, and D3-mediated actions are mainly inhibitory. Using an animal model of spinal sensorimotor dysfunction, the D3 receptor knockout mouse (D3KO), we investigated the physiological consequences of D3 receptor dysfunction on pain-associated signaling pathways in the spinal cord, the initial integration site for the processing of pain signaling. In the D3KO spinal cord, inhibitory actions of DA on the proprioceptive monosynaptic stretch reflex are converted from depression to facilitation, but its effects on longer-latency and pain-associated reflex responses and the effects of FM have not been studied. Using behavioral approaches in vivo, we found that D3KO animals exhibit reduced paw withdrawal latencies to thermal pain stimulation (Hargreaves' test) over wild type (WT) controls. Electrophysiological and pharmacological approaches in the isolated spinal cord in vitro showed that constant current stimulation of dorsal roots at a pain-associated frequency was associated with a significant reduction in the frequency-dependent modulation of longer-latency reflex (LLRs) responses but not monosynaptic stretch reflexes (MSRs) in D3KO. Application of the D1 and D2 receptor agonists and the voltage-gated calcium-channel ligand, pregabalin, but not DA, was able to restore the frequency-dependent modulation of the LLR in D3KO to WT levels. Thus we demonstrate that nociception-associated LLRs and proprioceptive MSRs are differentially modulated by frequency, dopaminergics and the Ca(2+) channel ligand, pregabalin. Our data suggest a role for the DA D3 receptor in pain modulation and identify the D3KO as a possible model for increased nociception. Copyright © 2012 Elsevier Inc. All rights reserved.

Vardenafil improves ejaculation success rates and self-confidence in men with erectile dysfunction due to spinal cord injury.

PubMed

Giuliano, Francois; Rubio-Aurioles, Eusebio; Kennelly, Michael; Montorsi, Francesco; Kim, Edward D; Finkbeiner, Alex E; Pommerville, Peter J; Colopy, Michael W; Wachs, Barton H

2008-04-01

Multicenter, double-blind, placebo-controlled, parallel-group study. To assess the effect of the oral phosphodiesterase type-5 inhibitor, vardenafil, on ejaculation rates and self-confidence in men with spinal cord injury (SCI). Spinal command of male sexual functions is often seriously impaired by traumatic spinal cord injury (SCI). A high proportion of men with SCI cannot ejaculate during sexual intercourse. SCI-related ejaculatory disorders are often responsible for male infertility. Sexual dysfunction associated with SCI can also affect men's self-confidence. In this 12-week study, 418 men aged >or=18 years with erectile dysfunction >6 months resulting from a traumatic SCI were randomized to vardenafil (n = 207) or placebo (n = 211) 10 mg for 4 weeks, then maintained or titrated to 5 or 20 mg at weeks 4 and 8. Assessments included questions of the International Index of Erectile Function (IIEF) about ejaculation success and orgasmic perception; the Global Confidence Question; and quality-of-life scales to measure psychological well-being, self-esteem, depression, and mental health status. Overall per patient ejaculation success rates were significantly greater with vardenafil than placebo over 12 weeks of treatment (19% vs. 10%; P < 0.001). At last observation carried forward, the IIEF "orgasmic function" score increased from 2.9 at baseline to 4.0 for vardenafil and from 3.0 at baseline to 3.4 for placebo. Sixteen percent of men receiving vardenafil and 8% receiving placebo felt orgasm "almost always" or "always" at weeks 8-12, compared with 4% and 6%, respectively, at baseline. Significant improvements in confidence scores were observed with vardenafil compared with placebo (P < 0.0001). There were no clinically significant differences between vardenafil and placebo in the quality-of-life measures at the study endpoint, but these had been in the normal range at baseline. Vardenafil significantly improved ejaculation and self-confidence in men with erectile dysfunction due to SCI.

Spinal Disinhibition in Experimental and Clinical Painful Diabetic Neuropathy

PubMed Central

Marshall, Andrew G.; Lee-Kubli, Corinne; Azmi, Shazli; Zhang, Michael; Ferdousi, Maryam; Mixcoatl-Zecuatl, Teresa; Petropoulos, Ioannis N.; Ponirakis, Georgios; Fineman, Mark S.; Fadavi, Hassan; Frizzi, Katie; Tavakoli, Mitra; Jolivalt, Corinne G.; Boulton, Andrew J.M.; Efron, Nathan; Calcutt, Nigel A.

2017-01-01

Impaired rate-dependent depression (RDD) of the Hoffman reflex is associated with reduced dorsal spinal cord potassium chloride cotransporter expression and impaired spinal γ-aminobutyric acid type A receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia. Impaired RDD in diabetic rats was rapidly normalized by spinal delivery of duloxetine acting via 5-hydroxytryptamine type 2A receptors and temporally coincident with the alleviation of allodynia. Deficits in RDD and corneal nerve density were demonstrated in patients with painful diabetic neuropathy compared with healthy control subjects and patients with painless diabetic neuropathy. Spinal inhibitory dysfunction and peripheral small fiber pathology may contribute to the clinical phenotype in painful diabetic neuropathy. Deficits in RDD may help identify patients with spinally mediated painful diabetic neuropathy who may respond optimally to therapies such as duloxetine. PMID:28202580

Methane ameliorates spinal cord ischemia-reperfusion injury in rats: Antioxidant, anti-inflammatory and anti-apoptotic activity mediated by Nrf2 activation.

PubMed

Wang, Liping; Yao, Ying; He, Rong; Meng, Yan; Li, Na; Zhang, Dan; Xu, Jiajun; Chen, Ouyang; Cui, Jin; Bian, Jinjun; Zhang, Yan; Chen, Guozhong; Deng, Xiaoming

2017-02-01

Methane is reported to have antioxidant, anti-inflammatory and anti-apoptotic properties. We investigated the potential neuroprotective effects of methane-rich saline (MS) on spinal cord ischemia-reperfusion injury and determined that its therapeutic benefits are associated with the activation of nuclear factor erythroid 2-related factor 2 (Nrf2). Rats received 9min of spinal cord ischemia induced by occlusion of the descending thoracic aorta plus systemic hypotension followed by a single MS treatment (10ml/kg, ip) and 72h reperfusion. MS treatment attenuated motor sensory deficits and produced high concentrations of methane in spinal cords during reperfusion, which increased Nrf2 expression and transcriptional activity in neurons, microglia and astrocytes in the ventral, intermediate and dorsal gray matter of lumbar segments. Heme oxygenase-1, superoxide dismutase, catalase and glutathione were upregulated; and glutathione disulfide, superoxide, hydrogen peroxide, malondialdehyde, 8-hydroxy-2-deoxyguanosine and 3-nitrotyrosine were downregulated in MS-treated spinal cords. MS treatment reduced neuronal apoptosis in gray matter zones, which was consistent with the suppression of cytochrome c release to the cytosol from the mitochondria and the activation of caspase-9 and -3. Throughout the gray matter, the activation of microglia and astrocytes was inhibited; the nuclear accumulation of phosphorylated nuclear factor-kappa B p65 was reduced; and tumor necrosis factor α, interleukin 1β, chemokine (C-X-C motif) ligand 1, intercellular adhesion molecule 1 and myeloperoxidase were decreased. MS treatment attenuated blood-spinal cord barrier dysfunction by preventing the expression and activity of matrix metallopeptidase-9 and disrupting tight junction proteins. Consecutive intrathecal injection of specific siRNAs targeting Nrf2 at 24-h intervals 3 days before ischemia reduced the beneficial effects of MS. Our data indicate that MS treatment prevents IR-induced spinal cord damage via antioxidant, anti-inflammatory and anti-apoptotic activities that involve the activation of Nrf2 signaling. Thus, methane may serve as a novel promising therapeutic agent for treating ischemic spinal cord injury. Copyright © 2016 Elsevier Inc. All rights reserved.

EFFECTS OF METHYLMERCURY ON SPINAL CORD AFFERENTS AND EFFERENTS—A REVIEW

PubMed Central

Colón-Rodríguez, Alexandra; Hannon, Heidi E.; Atchison, William D.

2017-01-01

Methylmercury (MeHg) is an environmental neurotoxicant of public health concern. It readily accumulates in exposed humans, primarily in neuronal tissue. Exposure to MeHg, either acutely or chronically, causes severe neuronal dysfunction in the central nervous system and spinal neurons; dysfunction of susceptible neuronal populations results in neurodegeneration, at least in part through Ca2+-mediated pathways. Biochemical and morphologic changes in peripheral neurons precede those in central brain regions, despite the fact that MeHg readily crosses the blood-brain barrier. Consequently, it is suggested that unique characteristics of spinal cord afferents and efferents could heighten their susceptibility to MeHg toxicity. Transient receptor potential (TRP) ion channels are a class of Ca2+-permeable cation channels that are highly expressed in spinal afferents, among other sensory and visceral organs. These channels can be activated in numerous ways, including directly via chemical irritants or indirectly via Ca2+ release from intracellular storage organelles. Early studies demonstrated that MeHg interacts with heterologous TRPs, though definitive mechanisms of MeHg toxicity on sensory neurons may involve more complex interaction with, and among, differentially-expressed TRP populations. In spinal efferents, glutamate receptors of the N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and possibly kainic acid (KA) classes are thought to play a major role in MeHg-induced neurotoxicity. Specifically, the Ca2+-permeable AMPA receptors, which are abundant in motor neurons, have been identified as being involved in MeHg-induced neurotoxicity. In this review, we will describe the mechanisms that could contribute to MeHg-induced spinal cord afferent and efferent neuronal degeneration, including the possible mediators, such as uniquely expressed Ca2+-permeable ion channels. PMID:28041893

Diabetes-induced microvascular complications at the level of the spinal cord; a contributing factor in diabetic neuropathic pain.

PubMed

Ved, N; Da Vitoria Lobo, M E; Bestall, S M; L Vidueira, C; Beazley-Long, N; Ballmer-Hofer, K; Hirashima, M; Bates, D O; Donaldson, L F; Hulse, R P

2018-05-17

Abnormalities of neurovascular interactions within the central nervous system of diabetic patients is associated with the onset of many neurological disease states. However, to date, the link between the neurovascular network within the spinal cord and regulation of nociception has not been investigated despite neuropathic pain being common in diabetes. We hypothesised that hyperglycaemia-induced endothelial degeneration in the spinal cord, due to suppression of VEGF-A/VEGFR2 signalling, induces diabetic neuropathic pain. Nociceptive pain behaviour was investigated in a chemically induced model of type 1 diabetes (streptozotocin induced, insulin supplemented; either vehicle or VEGF-A 165 b treated) and an inducible endothelial knockdown of VEGFR2 (tamoxifen induced). Diabetic animals developed mechanical allodynia and heat hyperalgesia. This was associated with a reduction in the number of blood vessels and reduction in Evans blue extravasation in the lumbar spinal cord of diabetic animals versus age-matched controls. Endothelial markers occludin, CD31 and VE-cadherin were downregulated in the spinal cord of the diabetic group versus controls, as well as a concurrent reduction of VEGF-A 165 b expression. In diabetic animals, VEGF-A 165 b treatment (biweekly intraperitoneal, 20 ng g -1 ) restored normal Evans blue extravasation and prevented vascular degeneration, diabetes-induced central neuron activation and neuropathic pain. Inducible knockdown of VEGFR2 (tamoxifen treated Tie2CreER T2 -vegfr2 flfl mice) led to a reduction in blood vessel network volume in the lumbar spinal cord and development of heat hyperalgesia. These findings indicate that hyperglycaemia leads to a reduction in the VEGF-A/VEGFR2 signalling cascade resulting in endothelial dysfunction in the spinal cord, which could be an undiscovered contributing factor to diabetic neuropathic pain. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Accumulation of p62 in degenerated spinal cord under chronic mechanical compression

PubMed Central

Tanabe, Fumito; Yone, Kazunori; Kawabata, Naoya; Sakakima, Harutoshi; Matsuda, Fumiyo; Ishidou, Yasuhiro; Maeda, Shingo; Abematsu, Masahiko; Komiya, Setsuro

2011-01-01

Intracellular accumulation of altered proteins, including p62 and ubiquitinated proteins, is the basis of most neurodegenerative disorders. The relationship among the accumulation of altered proteins, autophagy, and spinal cord dysfunction by cervical spondylotic myelopathy has not been clarified. We examined the expression of p62 and autophagy markers in the chronically compressed spinal cord of tiptoe-walking Yoshimura mice. In addition, we examined the expression and roles of p62 and autophagy in hypoxic neuronal cells. Western blot analysis showed the accumulation of p62, ubiquitinated proteins, and microtubule-associated protein 1 light chain 3 (LC3), an autophagic marker, in the compressed spinal cord. Immunohistochemical examinations showed that p62 accumulated in neurons, axons, astrocytes, and oligodendrocytes. Electron microscopy showed the expression of autophagy markers, including autolysosomes and autophagic vesicles, in the compressed spinal cord. These findings suggest the presence of p62 and autophagy in the degenerated compressed spinal cord. Hypoxic stress increased the expression of p62, ubiquitinated proteins, and LC3-II in neuronal cells. In addition, LC3 turnover assay and GFP-LC3 cleavage assay showed that hypoxic stress increased autophagy flux in neuronal cells. These findings suggest that hypoxic stress induces accumulation of p62 and autophagy in neuronal cells. The forced expression of p62 decreased the number of neuronal cells under hypoxic stress. These findings suggest that p62 accumulation under hypoxic stress promotes neuronal cell death. Treatment with 3-methyladenine, an autophagy inhibitor decreased the number of neuronal cells, whereas lithium chloride, an autophagy inducer increased the number of cells under hypoxic stress. These findings suggest that autophagy promotes neuronal cell survival under hypoxic stress. Our findings suggest that pharmacological inducers of autophagy may be useful for treating cervical spondylotic myelopathy patients. PMID:22082874

Electrical stimulation and motor recovery.

PubMed

Young, Wise

2015-01-01

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

The pathology of lumbosacral lipomas: macroscopic and microscopic disparity have implications for embryogenesis and mode of clinical deterioration.

PubMed

Jones, Victoria; Wykes, Victoria; Cohen, Nicki; Thompson, Dominic; Jacques, Tom S

2018-06-01

Lumbosacral lipomas (LSL) are congenital disorders of the terminal spinal cord region that have the potential to cause significant spinal cord dysfunction in children. They are of unknown embryogenesis with variable clinical presentation and natural history. It is unclear whether the spinal cord dysfunction reflects a primary developmental dysplasia or whether it occurs secondarily to mechanical traction (spinal cord tethering) with growth. While different anatomical subtypes are recognised and classified according to radiological criteria, these subtypes correlate poorly with clinical prognosis. We have undertaken an analysis of surgical specimens in order to describe the spectrum of histological changes that occur and have correlated the histology with the anatomical type of LSL to determine if there are distinct histological subtypes. The histopathology was reviewed of 64 patients who had undergone surgical resection of LSL. The presence of additional tissues and cell types were recorded. LSLs were classified from pre-operative magnetic resonance imaging (MRI) scans according to Chapman classification. Ninety-five per cent of the specimens consisted predominantly of mature adipocytes with all containing thickened bands of connective tissue and peripheral nerve fibres, 91% of samples contained ectatic blood vessels with thickened walls, while 22% contained central nervous system (CNS) glial tissue. Additional tissue was identified of both mesodermal and neuroectodermal origin. Our analysis highlights the heterogeneity of tissue types within all samples, not reflected in the nomenclature. The diversity of tissue types, consistent across all subtypes, challenges currently held notions regarding the embryogenesis of LSLs and the assumption that clinical deterioration is due simply to tethering. © 2018 The Authors. Histopathology Published by John Wiley & Sons Ltd.

Advances in the management of infertility in men with spinal cord injury

PubMed Central

Ibrahim, Emad; Brackett, Nancy L; Lynne, Charles M

2016-01-01

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

Management and outcomes of spinal epidural hematoma during vertebroplasty: Case series.

PubMed

Fang, Miao; Zhou, Jiaojiao; Yang, Dongjun; He, Yu; Xu, Yong; Liu, Xin; Zeng, Yong

2018-05-01

Spinal cord injury (SCI) is one of the common complications of spinal surgery. There is no definite treatment and time of decompression for spinal cord induced by epidural hematoma during vertebroplasty. A total of 6 patients with SCI during vertebroplasty were included in our research. All of them occurred sensory disturbance and motor dysfunction due to a lower or same level operative vertebral body lesion in vertebroplasty. Neurological manifestations during vertebroplasty, postoperative magnetic resonance imaging and computed tomography. Once SCI occurred in vertebroplasty, four patients were underwent spinal cord decompression immediately, and two patients were done after 14 and 22 hours, respectively. Before decompression operation, one patient was Frankel A, three were Frankel B, and two were Frankel C. One day after evacuation of the SEH, three patients recovered to normal neurological function (Frankel E), one to Frankel C, and one to Frankel D, but the other one did not recover. At the last follow-up, five patients had recovered to Frankel E and one patient to Frankel D. According to our experience, when SCI occurs during vertebroplasty, neurological deficits are always secondary to acute SEH. Timely decompression, particularly transfer surgery, can shorten recovery time.

[One-stage total en bloc spondylectomy and reconstruction via a single posterior approach for thoracic vertebral symptomatic hemangioma associated with spinal cord dysfunction].

PubMed

Song, Ruo-xian; Zhang, Yong-gang; Zhang, Xue-song; Zheng, Guo-quan; Wang, Yan

2012-04-01

To investigate the surgical results of one-stage total en bloc spondylectomy (TES) and reconstruction via a single posterior approach for thoracic symptomatic vertebral hemangioma associated with spinal cord dysfunction and evaluate its curative effect. A total of 9 patients treated with one-stage TES (7 cases) and total vertebrectomy (2 cases) by posterior approach from March 2006 to January 2010 were retrospectively reviewed. The cases included 2 males and 7 females with a median age of 33.6 years (range 14 to 77 years), and with 1 case of Grade A, 3 cases of Grade B, 3 cases of Grade C, 2 cases of Grade D according to Frankel grade system. All patients suffered from moderate to severe pain and neurological deficit with an average symptom duration of 14.4 months (range 3 - 24 months) MRI revealed severe spinal cord compression. The spinal reconstruction was obtained by titanium mesh filled with autograft and posterior internal fixation with rod-screw system. The operation time was 210 minutes on average (180 - 270 minutes) and the average blood loss was 1800 ml (1000 - 5000 ml). The follow-up period lasted from 18 months to 5 years. All cases with preoperative pain relieved after operation. The visual analogue scale pain scores decreased to 1.1 from 8.3 at 3 months after surgery. No disruption of dural mater, cerebrospinal fluid leakage, iatrogenic spinal cord injury and major vessel damage occurred. Up to now, there was no local recurrence in all cases. Significant neurological function improvement was achieved in all patients with one to three grades in Frankel grade system. Fusion of the autograft was well achieved and no internal fixation failure in all patients. One-stage TES and spine reconstruction by a single posterior approach is feasible, safe and effective to this disease. It is favourable in decreasing the hemangioma recurrence and improvement of the neurological function.

Efficacy and safety of vardenafil in men with erectile dysfunction caused by spinal cord injury.

PubMed

Giuliano, F; Rubio-Aurioles, E; Kennelly, M; Montorsi, F; Kim, E D; Finkbeiner, A E; Pommerville, P J; Colopy, M W; Wilkins, H J; Wachs, B H

2006-01-24

To assess the efficacy and tolerability of vardenafil in men with erectile dysfunction (ED) due to traumatic spinal cord injury (SCI). In this multicenter, double-blind, placebo-controlled, parallel-group 12-week study, 418 men aged 18 years and older with ED for more than 6 months consequent to SCI were randomized to vardenafil (n = 207) or placebo (n = 211) (10 mg for 4 weeks, then maintained or titrated to 5 or 20 mg at weeks 4 and 8). Efficacy assessments included the erectile function (EF) domain score of the International Index of Erectile Function questionnaire and diary questions regarding penetration, maintenance of erection to completion of intercourse, and ejaculation. Baseline patient characteristics were similar in the vardenafil (mean age 40 years) and placebo (mean age 39 years) groups. Mean baseline EF domain scores were 11.6 in the vardenafil group and 12.1 (moderate ED) in the placebo group. EF domain score in the vardenafil group improved to 22.0 (mild ED) at last observation carried forward vs 13.5 in the placebo group (p < 0.001). Over 12 weeks of treatment, mean per-patient penetration (76% vs 41%), maintenance (59% vs 22%), and ejaculation (19% vs 10%) success rates were significantly greater vs placebo (all p < 0.001). The most frequently reported drug-related adverse events were headache (vardenafil 15%, placebo 4%), flushing (vardenafil 6%, placebo 0%), nasal congestion (vardenafil 5%, placebo 0%), and dyspepsia (vardenafil 4%, placebo 0%). Vardenafil significantly improved erectile and ejaculatory function and was generally well tolerated in men with erectile dysfunction due to spinal cord injury.

Spinal cord compression in pseudohypoparathyroidism.

PubMed

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

2013-12-01

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

[HIV-associated myelopathy: an uncommon indicator of AIDS].

PubMed

Konaté, A; Ceballos, P; Rivière, S; Faucherre, V; Ciurana, A J; Le Quellec, A

2001-10-01

Spinal cord lesions are an uncommon mode of discovering acquired immunodeficiency syndrome because they usually appear at a later stage. We report a 58-year-old patient who had a spastic paraparesia and sphincter dysfunction. The spinal cord magnetic resonance imaging showed spontaneous hypersignals on T2-weighted images at the cervical and thoracic levels, enhanced with gadolinium, and without swelling. No cause was found. The HIV serology was positive and allowed us to consider an HIV-associated myelopathy. The antiretroviral therapy led to functional recovery. An HIV serology is suggested whenever an unexplained intramedullary lesion is discovered. Indeed, the diagnosis of HIV-associated myelopathy implies a specific therapeutic approach.

The excitatory amino acid receptor antagonist MK-801 prevents the hypersensitivity induced by spinal cord ischemia in the rat

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

Hao, J.X.; Xu, X.J.; Aldskogius, H.

1991-08-01

Protection by the NMDA receptor antagonist MK-801 against transient spinal cord ischemia-induced hypersensitivity was studied in rats. The spinal ischemia was initiated by vascular occlusion resulting from the interaction between the photosensitizing dye Erythrosin B and an argon laser beam. The hypersensitivity, termed allodynia, where the animals reacted by vocalization to nonnoxious mechanical stimuli in the flank area, was consistently observed during several days after induction of the ischemia. Pretreatment with MK-801 (0.1-0.5 mg/kg, iv) 10 min before laser irradiation dose dependently prevented the occurrence of allodynia. The neuroprotective effect of MK-801 was not reduced by maintaining normal body temperaturemore » during and after irradiation. There was a significant negative correlation between the delay in the administration of MK-801 after irradiation and the protective effect of the drug. Histological examination revealed slight morphological damage in the spinal cord in 38% of control rats after 1 min of laser irradiation without pretreatment with MK-801. No morphological abnormalities were observed in rats after pretreatment with MK-801 (0.5 mg/kg). The present results provide further evidence for the involvement of excitatory amino acids, through activation of the NMDA receptor, in the development of dysfunction following ischemic trauma to the spinal cord.« less

Relative shortening and functional tethering of spinal cord in adolescent scoliosis - Result of asynchronous neuro-osseous growth, summary of an electronic focus group debate of the IBSE.

PubMed

Chu, Winnie Cw; Lam, Wynnie Mw; Ng, Bobby Kw; Tze-Ping, Lam; Lee, Kwong-Man; Guo, Xia; Cheng, Jack Cy; Burwell, R Geoffrey; Dangerfield, Peter H; Jaspan, Tim

2008-06-27

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The Statement for this debate was written by Dr WCW Chu and colleagues who examine the spinal cord to vertebral growth interaction during adolescence in scoliosis. Using the multi-planar reconstruction technique of magnetic resonance imaging they investigated the relative length of spinal cord to vertebral column including ratios in 28 girls with AIS (mainly thoracic or double major curves) and 14 age-matched normal girls. Also evaluated were cerebellar tonsillar position, somatosensory evoked potentials (SSEPs), and clinical neurological examination. In severe AIS compared with normal controls, the vertebral column is significantly longer without detectable spinal cord lengthening. They speculate that anterior spinal column overgrowth relative to a normal length spinal cord exerts a stretching tethering force between the two ends, cranially and caudally leading to the initiation and progression of thoracic AIS. They support and develop the Roth-Porter concept of uncoupled neuro-osseous growth in the pathogenesis of AIS which now they prefer to term 'asynchronous neuro-osseous growth'. Morphological evidence about the curve apex suggests that the spinal cord is also affected, and a 'double pathology' is suggested. AIS is viewed as a disorder with a wide spectrum and a common neuroanatomical abnormality namely, a spinal cord of normal length but short relative to an abnormally lengthened anterior vertebral column. Neuroanatomical changes and/or abnormal neural function may be expressed only in severe cases. This asynchronous neuro-osseous growth concept is regarded as one component of a larger concept. The other component relates to the brain and cranium of AIS subjects because abnormalities have been found in brain (infratentorial and supratentorial) and skull (vault and base). The possible relevance of systemic melatonin-signaling pathway dysfunction, platelet calmodulin levels and putative vertebral vascular biology to the asynchronous neuro-osseous growth concept is discussed. A biomechanical model to test the spinal component of the concept is in hand. There is no published research on the biomechanical properties of the spinal cord for scoliosis specimens. Such research on normal spinal cords includes movements (kinematics), stress-strain responses to uniaxial loading, and anterior forces created by the stretched cord in forward flexion that may alter sagittal spinal shape during adolescent growth. The asynchronous neuro-osseous growth concept for the spine evokes controversy. Dr Chu and colleagues respond to five other concepts of pathogenesis for AIS and suggest that relative anterior spinal overgrowth and biomechanical growth modulation may also contribute to AIS pathogenesis.

Cardiovascular dysfunction following spinal cord injury

PubMed Central

Partida, Elizabeth; Mironets, Eugene; Hou, Shaoping; Tom, Veronica J.

2016-01-01

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

Associations Between Pre-Implant Psychosocial Factors and Spinal Cord Stimulation Outcome: Evaluation Using the MMPI-2-RF.

PubMed

Block, Andrew R; Marek, Ryan J; Ben-Porath, Yossef S; Kukal, Deborah

2017-01-01

Spinal cord stimulation (SCS) has variable effectiveness in controlling chronic pain. Previous research has demonstrated that psychosocial factors are associated with diminished results of SCS. The objective of this investigation is to examine associations between pre-implant psychological functioning as measured by the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) and SCS outcomes. SCS candidates at two sites (total N = 319) completed the MMPI-2-RF and measures of pain, emotional distress, and functional ability as part of a pre-implant psychological evaluation. At an average of 5 months post-implant, patients completed the measures of pain and emotional distress a second time. Poorer SCS outcomes and poorer patient satisfaction were associated with higher pre-implant MMPI-2-RF scores on scales used to assess emotional dysfunction, somatic/cognitive complaints, and interpersonal problems. Ways through which pre-implant psychological evaluations of spinal cord stimulator candidates can be informed by MMPI-2-RF findings are discussed. © The Author(s) 2015.

Abdominal Manual Therapy Repairs Interstitial Cells of Cajal and Increases Colonic c-Kit Expression When Treating Bowel Dysfunction after Spinal Cord Injury

PubMed Central

Zhang, Wenyi; Zhu, Zhaojin; Xie, Bin; Yu, Jun

2017-01-01

Background This study aimed to evaluate the therapeutic effects of abdominal manual therapy (AMT) on bowel dysfunction after spinal cord injury (SCI), investigating interstitial cells of Cajal (ICCs) and related c-kit expression. Methods Model rats were divided as SCI and SCI with drug treatment (intragastric mosapride), low-intensity (SCI + LMT; 50 g, 50 times/min), and high-intensity AMT (SCI + HMT; 100 g, 150 times/min). After 14 days of treatment, weight, improved Basso-Beattie-Bresnahan (BBB) locomotor score, and intestinal movement were evaluated. Morphological structure of spinal cord and colon tissues were examined. Immunostaining, RT-PCR, and western blot were used to assess c-kit expression. Results In SCI rats, AMT could not restore BBB, but it significantly increased weight, shortened time to defecation, increased feces amounts, and improved fecal pellet traits and colon histology. AMT improved the number, distribution, and ultrastructure of colonic ICCs, increasing colonic c-kit mRNA and protein levels. Compared with the SCI + Drug and SCI + LMT groups, the SCI + HMT group showed better therapeutic effect in improving intestinal transmission function and promoting c-kit expression. Conclusions AMT is an effective therapy for recovery of intestinal transmission function. It could repair ICCs and increase c-kit expression in colon tissues after SCI, in a frequency-dependent and pressure-dependent manner. PMID:29349063

Alpha-1 adrenoceptor hyperresponsiveness in three neuropathic pain states: complex regional pain syndrome 1, diabetic peripheral neuropathic pain and central pain states following spinal cord injury.

PubMed

Teasell, Robert W; Arnold, J Malcolm O

2004-01-01

The pathophysiology of the pain associated with complex regional pain syndrome, spinal cord injury and diabetic peripheral neuropathy is not known. The pain of complex regional pain syndrome has often been attributed to abnormal sympathetic nervous system activity based on the presence of vasomotor instability and a frequently reported positive response, albeit a temporary response, to sympathetic blockade. In contrast, the pain below the level of spinal cord injury and diabetic peripheral neuropathy are generally seen as deafferentation phenomena. Each of these pain states has been associated with abnormal sympathetic nervous system function and increased peripheral alpha-1 adrenoceptor activity. This increased responsiveness may be a consequence of alpha-1 adrenoceptor postsynaptic hypersensitivity, or alpha-2 adrenoceptor presynaptic dysfunction with diminished noradrenaline reuptake, increased concentrations of noradrenaline in the synaptic cleft and increased stimulation of otherwise normal alpha-1 adrenoceptors. Plausible mechanisms based on animal research by which alpha-1 adrenoceptor hyperresponsiveness can lead to chronic neuropathic-like pain have been reported. This raises the intriguing possibility that sympathetic nervous system dysfunction may be an important factor in the generation of pain in many neuropathic pain states. Although results to date have been mixed, there may be a greater role for new drugs which target peripheral alpha-2 adrenoceptors (agonists) or alpha-1 adrenoceptors (antagonists).

Effects of Dietary Vitamin E Supplementation in Bladder Function and Spasticity during Spinal Cord Injury

PubMed Central

Cordero, Kathia; Coronel, Gemma G.; Serrano-Illán, Miguel; Cruz-Bracero, Jennifer

2018-01-01

Traumatic spinal cord injury (SCI) results in debilitating autonomic dysfunctions, paralysis and significant sensorimotor impairments. A key component of SCI is the generation of free radicals that contributes to the high levels of oxidative stress observed. This study investigates whether dietary supplementation with the antioxidant vitamin E (alpha-tocopherol) improves functional recovery after SCI. Female adult Sprague-Dawley rats were fed either with a normal diet or a dietary regiment supplemented with vitamin E (51 IU/g) for eight weeks. The rats were subsequently exposed either to a contusive SCI or sham operation, and evaluated using standard functional behavior analysis. We report that the rats that consumed the vitamin E-enriched diet showed an accelerated bladder recovery and significant improvements in locomotor function relative to controls, as determined by residual volumes and Basso, Beatie, and Bresnaham BBB scores, respectively. Interestingly, the prophylactic dietary intervention did not preserve neurons in the ventral horn of injured rats, but it significantly increased the numbers of oligodendrocytes. Vitamin E supplementation attenuated the depression of the H-reflex (a typical functional consequence of SCI) while increasing the levels of supraspinal serotonin immunoreactivity. Our findings support the potential complementary use of vitamin E to ameliorate sensory and autonomic dysfunctions associated with spinal cord injury, and identified promising new cellular and functional targets of its neuroprotective effects. PMID:29495419

Sexual responsiveness in women with spinal cord injuries: differential effects of anxiety-eliciting stimulation.

PubMed

Sipski, Marca L; Rosen, Raymond C; Alexander, Craig J; Gómez-Marín, Orlando

2004-06-01

Sexual dysfunction is a common problem in women after spinal cord injuries (SCIs). Recently, the use of anxiety-provoking stimulation has been explored as a means of improving sexual responses in able-bodied sexually functional and dysfunctional women. In this laboratory-based study, we assessed the sexual and autonomic responses of women with SCIs with varying degrees of preservation of sympathetic innervation to their genitals to respond to anxiety-provoking audiovisual (AV) stimulation. Subjects were 45 women with SCIs and 11 able-bodied women. For purposes of analysis, SCI subjects were grouped on the basis of the degree of preservation of sensation in the T11-L2 dermatomes. Results revealed that women with low sensory scores in these dermatomes achieved higher vaginal pulse amplitude (VPA) responses to audiovisual erotic stimulation after anxiety preexposure than after neutral preexposure; however, women with SCIs and the greatest degree of preservation of sensory function in the T11-L2 dermatomes, as well as able-bodied controls, did not. Moreover, these same 2 groups of subjects had a decrease in VPA responses during baseline periods in which an anxiety-provoking video sequence was shown, but not during the neutral sequence. It is concluded that these findings are due to the proximity of sensory and autonomic neurologic elements in the spinal cord. Moreover, they demonstrate the differential effects of sympathetic stimulation on genital sexual arousal.

Progress in Paralysis | NIH MedlinePlus the Magazine

MedlinePlus

... benefits from this research flowing to people with Parkinson's disease or other neurological disorders? The mechanism of dysfunction in spinal cord injury is not completely understood but is believed to be ... Parkinson's and some of the other neurological disorders. Consequently, ...

The Blood-Testis Barrier and Male Sexual Dysfunction following Spinal Cord Injury

DTIC Science & Technology

2014-10-01

antigenic sperm and sperm cell-containing compartments within the testis. We also demonstrated that once failed, the BTB remains permeable, essentially...input into the male sexual organs. SCI-dependent male infertility is characterized by a significant reduction in numbers and quality of functional... sperm . The mechanism(s) underlying this deficit has previously been unknown. My laboratory has explored the effects of spinal trauma on tissues that

The Blood Testis Barrier and Male Sexual Dysfunction following Spinal Cord Injury

DTIC Science & Technology

2015-10-01

sensory and motor deficits . In addition to these well-described pathological outcomes, a majority of men will also experience greatly diminished...underlying this deficit has previously been unknown. We have explored the effects of spinal trauma on tissues that exhibit “barrier” properties, or...immune cell infiltration. The goal of this project is to: 1) further elaborate the early and long-term biochemical, molecular and structural deficits

Brain and spinal cord interaction: a dietary curcumin derivative counteracts locomotor and cognitive deficits after brain trauma.

PubMed

Wu, Aiguo; Ying, Zhe; Schubert, David; Gomez-Pinilla, Fernando

2011-05-01

In addition to cognitive dysfunction, locomotor deficits are prevalent in traumatic brain injured (TBI) patients; however, it is unclear how a concussive injury can affect spinal cord centers. Moreover, there are no current efficient treatments that can counteract the broad pathology associated with TBI. The authors have investigated potential molecular basis for the disruptive effects of TBI on spinal cord and hippocampus and the neuroprotection of a curcumin derivative to reduce the effects of experimental TBI. The authors performed fluid percussion injury (FPI) and then rats were exposed to dietary supplementation of the curcumin derivative (CNB-001; 500 ppm). The curry spice curcumin has protective capacity in animal models of neurodegenerative diseases, and the curcumin derivative has enhanced brain absorption and biological activity. The results show that FPI in rats, in addition to reducing learning ability, reduced locomotor performance. Behavioral deficits were accompanied by reductions in molecular systems important for synaptic plasticity underlying behavioral plasticity in the brain and spinal cord. The post-TBI dietary supplementation of the curcumin derivative normalized levels of BDNF, and its downstream effectors on synaptic plasticity (CREB, synapsin I) and neuronal signaling (CaMKII), as well as levels of oxidative stress-related molecules (SOD, Sir2). These studies define a mechanism by which TBI can compromise centers related to cognitive processing and locomotion. The findings also show the influence of the curcumin derivative on synaptic plasticity events in the brain and spinal cord and emphasize the therapeutic potential of this noninvasive dietary intervention for TBI.

International spinal cord injury bowel function basic data set (Version 2.0).

PubMed

Krogh, K; Emmanuel, A; Perrouin-Verbe, B; Korsten, M A; Mulcahey, M J; Biering-Sørensen, F

2017-07-01

International expert working group. To revise the International Spinal Cord Injury (SCI) Bowel Function Basic Data Set as a standardized format for the collecting and reporting of a minimal amount of information on bowel function in clinical practice and research. Working group appointed by the American Spinal injury association (ASIA) and the International Spinal Cord Society (ISCoS). The draft prepared by the working group was reviewed by the International SCI Data Set Committee and later by members of the ISCoS Executive and Scientific Committees and the ASIA board. The revised data set was posted on the ASIA and ISCoS websites for 1 month to allow further comments and suggestions. Changes resulting from a Delphi process among experts in children with SCI were included. Members of ISCoS Executive and Scientific Committees and the ASIA board made a final review and approved the data set. The International SCI Bowel Function Basic Data Set (Version 2.0) consists of the following 16 items: date of data collection, gastrointestinal and anal sphincter dysfunction unrelated to SCI, surgical procedures on the gastrointestinal tract, defecation method and bowel-care procedures, average time required for defecation, frequency of defecation, uneasiness, headache or perspiration during defecation, digital stimulation or evacuation of the anorectum, frequency of fecal incontinence, flatus incontinence, need to wear pad or plug, oral laxatives and prokinetics, anti-diarrheal agents, perianal problems, abdominal pain and discomfort and the neurogenic bowel dysfunction score. The International SCI Bowel Function Basic Data Set (Version 2.0) has been developed.

Association of myelopathy scores with cervical sagittal balance and normalized spinal cord volume: analysis of 56 preoperative cases from the AOSpine North America Myelopathy study.

PubMed

Smith, Justin S; Lafage, Virginie; Ryan, Devon J; Shaffrey, Christopher I; Schwab, Frank J; Patel, Alpesh A; Brodke, Darrel S; Arnold, Paul M; Riew, K Daniel; Traynelis, Vincent C; Radcliff, Kris; Vaccaro, Alexander R; Fehlings, Michael G; Ames, Christopher P

2013-10-15

Post hoc analysis of prospectively collected data. Development of methods to determine in vivo spinal cord dimensions and application to correlate preoperative alignment, myelopathy, and health-related quality-of-life scores in patients with cervical spondylotic myelopathy (CSM). CSM is the leading cause of spinal cord dysfunction. The association between cervical alignment, sagittal balance, and myelopathy has not been well characterized. This was a post hoc analysis of the prospective, multicenter AOSpine North America CSM study. Inclusion criteria for this study required preoperative cervical magnetic resonance imaging (MRI) and neutral sagittal cervical radiography. Techniques for MRI assessment of spinal cord dimensions were developed. Correlations between imaging and health-related quality-of-life scores were assessed. Fifty-six patients met inclusion criteria (mean age = 55.4 yr). The modified Japanese Orthopedic Association (mJOA) scores correlated with C2-C7 sagittal vertical axis (SVA) (r = -0.282, P = 0.035). Spinal cord volume correlated with cord length (r = 0.472, P < 0.001) and cord average cross-sectional area (r = 0.957, P < 0.001). For all patients, no correlations were found between MRI measurements of spinal cord length, volume, mean cross-sectional area or surface area, and outcomes. For patients with cervical lordosis, mJOA scores correlated positively with cord volume (r = 0.366, P = 0.022), external cord area (r = 0.399, P = 0.012), and mean cross-sectional cord area (r = 0.345, P = 0.031). In contrast, for patients with cervical kyphosis, mJOA scores correlated negatively with cord volume (r = -0.496, P = 0.043) and mean cross-sectional cord area (r = -0.535, P = 0.027). This study is the first to correlate cervical sagittal balance (C2-C7 SVA) to myelopathy severity. We found a moderate negative correlation in kyphotic patients of cord volume and cross-sectional area to mJOA scores. The opposite (positive correlation) was found for lordotic patients, suggesting a relationship of cord volume to myelopathy that differs on the basis of sagittal alignment. It is interesting to note that sagittal balance but not kyphosis is tied to myelopathy score. Future work will correlate alignment changes to cord morphology changes and myelopathy outcomes. SUMMARY STATEMENTS: This is the first study to correlate sagittal balance (C2-C7 SVA) to myelopathy severity. We found a moderate negative correlation in kyphotic patients of cord volume and cross-sectional area to mJOA scores. The opposite (positive correlation) was found for lordotic patients, suggesting a relationship of cord volume to myelopathy that differs on the basis of sagittal alignment.

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL): assessment of the involved white matter tracts by MRI.

PubMed

Kassem, Hassan; Wafaie, Ahmed; Abdelfattah, Sherif; Farid, Tarek

2014-01-01

Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a recently identified autosomal recessive disorder with early onset of symptoms and slowly progressive pyramidal, cerebellar and dorsal column dysfunction. LBSL is characterized by distinct white matter abnormalities and selective involvement of brainstem and spinal cord tracts. The purpose of this study is to assess the imaging features of the involved white matter tracts in cases of LBSL by MRI. We retrospectively reviewed the imaging features of the selectively involved white matter tracts in sixteen genetically proven cases of leukoencephalopathy with brainstem and spinal cord involvement and elevated brain lactate (LBSL). All patients presented with slowly progressive cerebellar sensory ataxia with spasticity and dorsal column dysfunction. MRI of the brain and spine using 1.5 T machine and proton magnetic resonance spectroscopy (1H MRS) on the abnormal white matter were done to all patients. The MRI and MRS data sets were analyzed according to lesion location, extent, distribution and signal pattern as well as metabolite values and ratios in MRS. Laboratory examinations ruled out classic leukodystrophies. In all cases, MRI showed high signal intensity in T2-weighted and FLAIR images within the cerebral subcortical, periventricular and deep white matter, posterior limbs of internal capsules, centrum semiovale, medulla oblongata, intraparenchymal trajectory of trigeminal nerves and deep cerebellar white matter. In the spine, the signal intensity of the dorsal column and lateral cortico-spinal tracts were altered in all patients. The subcortical U fibers, globi pallidi, thalami, midbrain and transverse pontine fibers were spared in all cases. In 11 cases (68.8%), the signal changes were inhomogeneous and confluent whereas in 5 patients (31.2%), the signal abnormalities were spotty. MRI also showed variable signal abnormalities in the sensory and pyramidal tracts in addition to the brainstem and cerebellar connections. Proton MRS showed consistent elevation of the lactate within the abnormal white matter. Distinct MRI findings in the form of selective affection of subcortical and deep white matter tracts of the brain (involving the posterior limb of internal capsules and sparing the subcortical U fibers), dorsal column and lateral cortico-spinal tracts of the spinal cord should lead to the diagnosis of LBSL supported by the presence of lactate peak in 1H MRS. The disease can be confirmed by the analysis of the disease gene DARS2.

Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury.

PubMed

Ryge, Jesper; Winther, Ole; Wienecke, Jacob; Sandelin, Albin; Westerdahl, Ann-Charlotte; Hultborn, Hans; Kiehn, Ole

2010-06-09

Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be used to alter the transcriptional response to prevent the motor neurons from entering a state of hyper-excitability.

Accumulation of p62 in degenerated spinal cord under chronic mechanical compression: functional analysis of p62 and autophagy in hypoxic neuronal cells.

PubMed

Tanabe, Fumito; Yone, Kazunori; Kawabata, Naoya; Sakakima, Harutoshi; Matsuda, Fumiyo; Ishidou, Yasuhiro; Maeda, Shingo; Abematsu, Masahiko; Komiya, Setsuro; Setoguchi, Takao

2011-12-01

Intracellular accumulation of altered proteins, including p62 and ubiquitinated proteins, is the basis of most neurodegenerative disorders. The relationship among the accumulation of altered proteins, autophagy, and spinal cord dysfunction by cervical spondylotic myelopathy has not been clarified. We examined the expression of p62 and autophagy markers in the chronically compressed spinal cord of tiptoe-walking Yoshimura mice. In addition, we examined the expression and roles of p62 and autophagy in hypoxic neuronal cells. Western blot analysis showed the accumulation of p62, ubiquitinated proteins, and microtubule-associated protein 1 light chain 3 (LC3), an autophagic marker, in the compressed spinal cord. Immunohistochemical examinations showed that p62 accumulated in neurons, axons, astrocytes, and oligodendrocytes. Electron microscopy showed the expression of autophagy markers, including autolysosomes and autophagic vesicles, in the compressed spinal cord. These findings suggest the presence of p62 and autophagy in the degenerated compressed spinal cord. Hypoxic stress increased the expression of p62, ubiquitinated proteins, and LC3-II in neuronal cells. In addition, LC3 turnover assay and GFP-LC3 cleavage assay showed that hypoxic stress increased autophagy flux in neuronal cells. These findings suggest that hypoxic stress induces accumulation of p62 and autophagy in neuronal cells. The forced expression of p62 decreased the number of neuronal cells under hypoxic stress. These findings suggest that p62 accumulation under hypoxic stress promotes neuronal cell death. Treatment with 3-methyladenine, an autophagy inhibitor decreased the number of neuronal cells, whereas lithium chloride, an autophagy inducer increased the number of cells under hypoxic stress. These findings suggest that autophagy promotes neuronal cell survival under hypoxic stress. Our findings suggest that pharmacological inducers of autophagy may be useful for treating cervical spondylotic myelopathy patients.

Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury

PubMed Central

2010-01-01

Background Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. Results Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. Conclusions This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be used to alter the transcriptional response to prevent the motor neurons from entering a state of hyper-excitability. PMID:20534130

Age Related Changes in Metabolite Concentrations in the Normal Spinal Cord

PubMed Central

Abdel-Aziz, Khaled; Solanky, Bhavana S.; Yiannakas, Marios C.; Altmann, Daniel R.; Wheeler-Kingshott, Claudia A. M.; Thompson, Alan J.; Ciccarelli, Olga

2014-01-01

Magnetic resonance spectroscopy (MRS) studies have previously described metabolite changes associated with aging of the healthy brain and provided insights into normal brain aging that can assist us in differentiating age-related changes from those associated with neurological disease. The present study investigates whether age-related changes in metabolite concentrations occur in the healthy cervical spinal cord. 25 healthy volunteers, aged 23–65 years, underwent conventional imaging and single-voxel MRS of the upper cervical cord using an optimised point resolved spectroscopy sequence on a 3T Achieva system. Metabolite concentrations normalised to unsuppressed water were quantified using LCModel and associations between age and spinal cord metabolite concentrations were examined using multiple regressions. A linear decline in total N-Acetyl-aspartate concentration (0.049 mmol/L lower per additional year of age, p = 0.010) and Glutamate-Glutamine concentration (0.054 mmol/L lower per additional year of age, p = 0.002) was seen within our sample age range, starting in the early twenties. The findings suggest that neuroaxonal loss and/or metabolic neuronal dysfunction, and decline in glutamate-glutamine neurotransmitter pool progress with aging. PMID:25310093

The artificial somato-autonomic reflex arch does not improve lower urinary tract function in patients with spinal cord lesions.

PubMed

Rasmussen, Mikkel Mylius; Rawashdeh, Yazan F; Clemmensen, Dorte; Tankisi, Hatice; Fuglsang-Frederiksen, Anders; Krogh, Klaus; Christensen, Peter

2015-02-01

The artificial somato-autonomic reflex arch (Xiao procedure) was proposed as treatment for neurogenic bladder dysfunction. We investigated the effects of the procedure on lower urinary tract function. Seven and 3 patients with a median age of 46 years (range 19 to 64) had AIS A and B spinal cord injury, respectively. In these patients an anastomosis was created between the ventral (motor) part of L5 and the ventral part of the S2 root. Urodynamics were performed and a standard questionnaire was completed at baseline and 18 months postoperatively. Artificial reflex arch stimulation did not initiate voiding or increase bladder pressure. Maximum bladder capacity did not change significantly from baseline to followup (median 427.5 ml, range 168 to 581 vs 498.5, range 271 to 580, p = 0.09). Likewise, bladder compliance did not significantly differ at baseline and followup (median 16.9 ml/cm H2O, range 15.0 to 65.0 vs 25.1, range 17.5 to 50.0, p = 0.95). No difference was found in awareness of bladder emptying, incontinence episodes, bladder emptying method or medication use for neurogenic bladder dysfunction. The only statistically significant change was a decreased incidence of leakage at followup on urodynamics (p = 0.03). Postoperatively decreased genital sensation and erectile dysfunction developed in 1 patient and another experienced a minor cerebrovascular accident with no long-term complications. In contrast to earlier findings, creation of an artificial somato-autonomic reflex arch in patients with spinal cord injury had no clinically relevant effect on lower urinary tract function. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Intraoperative monitoring of somatosensory (SSEPs) and transcranial electric motor-evoked potentials (tce-MEPs) during surgical correction of neuromuscular scoliosis in patients with central or peripheral nervous system diseases.

PubMed

Pastorelli, F; Di Silvestre, M; Vommaro, F; Maredi, E; Morigi, A; Bacchin, M R; Bonarelli, S; Plasmati, R; Michelucci, R; Greggi, T

2015-11-01

Combined intraoperative monitoring (IOM) of transcranial electric motor-evoked potentials (tce-MEPs) and somatosensory-evoked potentials (SSEPs) is safe and effective for spinal cord monitoring during scoliosis surgery. However, the literature data regarding the reliability of spinal cord monitoring in patients with neuromuscular scoliosis are conflicting and need to be confirmed. We reviewed IOM records of 40 consecutive patients with neuromuscular scoliosis related to central nervous system (CNS) (29 pts) or peripheral nervous system (PNS) (11 patients) diseases, who underwent posterior fusion with instrumentation surgery for spinal deformity. Multimodalitary IOM with SSEPs and tce-MEPs was performed. Spinal cord monitoring using at least one modality was attempted in 38/40 (95 %) patients. No false-negative results were present in either group, but a relatively high incidence of false-positive cases (4/29, 13.8 %) was noted in the CNS group. Two patients in the CNS group and one patient in the PNS group presented transient postoperative motor deficits (true positive), related to surgical manoeuvres in two cases and to malposition in the other one. Multimodalitary IOM is safe and effective to detect impending spinal cord and peripheral nerves dysfunction in neuromuscular scoliosis surgery. However, the interpretation of neurophysiological data may be challenging in such patients, and the rate of false-positive results is high when pre-operatory motor deficits are severe.

The effect of thalidomide on spinal cord ischemia/reperfusion injury in a rabbit model.

PubMed

Lee, C-J; Kim, K-W; Lee, H-M; Nahm, F S; Lim, Y-J; Park, J-H; Kim, C-S

2007-02-01

Randomized study. To evaluate the effects of thalidomide on spinal cord ischemia/reperfusion injury via reduced TNF-alpha production. Animal experimental laboratory, Clinical Research Institute of Seoul National University Hospital, Seoul, Korea. Spinal cord ischemia was induced in rabbits by occluding the infrarenal aorta. Rabbits in group N did not undergo ischemic insult, but rabbits in groups C (the untreated group), THA, and THB underwent ischemic insult for 15 min. The THA and THB groups received thalidomide (20 mg/kg) intraperitoneally (i.p.) before ischemia, but only the THB group received thalidomide (i.p., 20 mg/kg) after 24 and 48 h of reperfusion. After evaluating neurologic functions at 1.5 h, 3, and 5 days of reperfusion, rabbits were killed for histopathologic examination and Western blot analysis of TNF-alpha. The THA and THB groups showed significantly less neurologic dysfunction than the C group at 1.5 h, 3, and 5 days of reperfusion. The number of normal spinal motor neurons in ventral gray matter was higher in THA and THB than in C, but no difference was observed between THA and THB. Western blot analysis showed a significantly higher level of TNF-alpha in C than in THA and THB at 1.5 h of reperfusion, but no difference was observed between C, THA, or THB at 3 or 5 days of reperfusion. Thalidomide treatment before ischemic insult reduces early phase ischemia/reperfusion injury of the spinal cord in rabbits.

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

PubMed

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

2014-01-01

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

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

PubMed Central

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

2014-01-01

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

Focal dysfunction of the proteasome: a pathogenic factor in a mouse model of amyotrophic lateral sclerosis.

PubMed

Kabashi, Edor; Agar, Jeffrey N; Taylor, David M; Minotti, Sandra; Durham, Heather D

2004-06-01

Mutations in the Cu/Zn-superoxide dismutase (SOD-1) gene are responsible for a familial form of amyotrophic lateral sclerosis (fALS). The present study demonstrated impaired proteasomal function in the lumbar spinal cord of transgenic mice expressing human SOD-1 with the ALS-causing mutation G93A (SOD-1(G93A)) compared to non-transgenic littermates (LM) and SOD-1(WT) transgenic mice. Chymotrypsin-like activity was decreased as early as 45 days of age. By 75 days, chymotrypsin-, trypsin-, and caspase-like activities of the proteasome were impaired, at about 50% of control activity in lumbar spinal cord, but unchanged in thoracic spinal cord and liver. Both total and specific activities of the proteasome were reduced to a similar extent, indicating that a change in proteasome function, rather than a decrease in proteasome levels, had occurred. Similar decreases of total and specific activities of the proteasome were observed in NIH 3T3 cell lines expressing fALS mutants SOD-1(G93A) and SOD-1(G41S), but not in SOD-1(WT) controls. Although overall levels of proteasome were maintained in spinal cord of SOD-1(G93A) transgenic mice, the level of 20S proteasome was substantially reduced in lumbar spinal motor neurons relative to the surrounding neuropil. It is concluded that impairment of the proteasome is an early event and contributes to ALS pathogenesis.

The crossed phrenic phenomenon

PubMed Central

Ghali, Michael George Zaki

2017-01-01

The cervical spine is the most common site of traumatic vertebral column injuries. Respiratory insufficiency constitutes a significant proportion of the morbidity burden and is the most common cause of mortality in these patients. In seeking to enhance our capacity to treat specifically the respiratory dysfunction following spinal cord injury, investigators have studied the “crossed phrenic phenomenon”, wherein contraction of a hemidiaphragm paralyzed by a complete hemisection of the ipsilateral cervical spinal cord above the phrenic nucleus can be induced by respiratory stressors and recovers spontaneously over time. Strengthening of latent contralateral projections to the phrenic nucleus and sprouting of new descending axons have been proposed as mechanisms contributing to the observed recovery. We have recently demonstrated recovery of spontaneous crossed phrenic activity occurring over minutes to hours in C1-hemisected unanesthetized decerebrate rats. The specific neurochemical and molecular pathways underlying crossed phrenic activity following injury require further clarification. A thorough understanding of these is necessary in order to develop targeted therapies for respiratory neurorehabilitation following spinal trauma. Animal studies provide preliminary evidence for the utility of neuropharmacological manipulation of serotonergic and adenosinergic pathways, nerve grafts, olfactory ensheathing cells, intraspinal microstimulation and a possible role for dorsal rhizotomy in recovering phrenic activity following spinal cord injury PMID:28761411

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

NASA Astrophysics Data System (ADS)

Ahmed, Zaghloul

2017-10-01

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

Amelioration of motor/sensory dysfunction and spasticity in a rat model of acute lumbar spinal cord injury by human neural stem cell transplantation

PubMed Central

2013-01-01

Introduction Intraspinal grafting of human neural stem cells represents a promising approach to promote recovery of function after spinal trauma. Such a treatment may serve to: I) provide trophic support to improve survival of host neurons; II) improve the structural integrity of the spinal parenchyma by reducing syringomyelia and scarring in trauma-injured regions; and III) provide neuronal populations to potentially form relays with host axons, segmental interneurons, and/or α-motoneurons. Here we characterized the effect of intraspinal grafting of clinical grade human fetal spinal cord-derived neural stem cells (HSSC) on the recovery of neurological function in a rat model of acute lumbar (L3) compression injury. Methods Three-month-old female Sprague–Dawley rats received L3 spinal compression injury. Three days post-injury, animals were randomized and received intraspinal injections of either HSSC, media-only, or no injections. All animals were immunosuppressed with tacrolimus, mycophenolate mofetil, and methylprednisolone acetate from the day of cell grafting and survived for eight weeks. Motor and sensory dysfunction were periodically assessed using open field locomotion scoring, thermal/tactile pain/escape thresholds and myogenic motor evoked potentials. The presence of spasticity was measured by gastrocnemius muscle resistance and electromyography response during computer-controlled ankle rotation. At the end-point, gait (CatWalk), ladder climbing, and single frame analyses were also assessed. Syrinx size, spinal cord dimensions, and extent of scarring were measured by magnetic resonance imaging. Differentiation and integration of grafted cells in the host tissue were validated with immunofluorescence staining using human-specific antibodies. Results Intraspinal grafting of HSSC led to a progressive and significant improvement in lower extremity paw placement, amelioration of spasticity, and normalization in thermal and tactile pain/escape thresholds at eight weeks post-grafting. No significant differences were detected in other CatWalk parameters, motor evoked potentials, open field locomotor (Basso, Beattie, and Bresnahan locomotion score (BBB)) score or ladder climbing test. Magnetic resonance imaging volume reconstruction and immunofluorescence analysis of grafted cell survival showed near complete injury-cavity-filling by grafted cells and development of putative GABA-ergic synapses between grafted and host neurons. Conclusions Peri-acute intraspinal grafting of HSSC can represent an effective therapy which ameliorates motor and sensory deficits after traumatic spinal cord injury. PMID:23710605

Measurements of C-reactive protein (CRP) and nerve-growth-factor (NGF) concentrations in serum and urine samples of dogs with neurologic disorders.

PubMed

Kordass, Ulrike; Carlson, Regina; Stein, Veronika Maria; Tipold, Andrea

2016-01-08

The purpose of this study was to prove the hypothesis that C-reactive protein (CRP) and nerve growth factor (NGF) may be potential biomarkers for lower urinary tract disorders and may be able to distinguish between micturition dysfunctions of different origin in dogs with spinal cord diseases. NGF- and CRP- concentrations were measured in serum and urine samples using specific ELISA-Kits. Results in urine were standardized by urine-creatinine levels. CRP in serum was detectable in 32/76 and in urine samples in 40/76 patients. NGF could be measured in all serum and in 70/76 urine samples. Urinary CRP concentrations were significantly higher in dogs with micturition dysfunction (p = 0.0009) and in dogs with different neurological diseases (p = 0.0020) compared to the control group. However, comparing dogs with spinal cord disorders with and without associated micturition dysfunction no significant difference could be detected for NGF and CRP values in urine or serum samples. Additionally, levels did not decrease significantly, when measured at the time when the dogs regained the ability to urinate properly (urinary NGF p = 0.7962; urinary CRP p = 0.078). Urine samples with bacteria and/or leukocytes had no significant increase in urinary NGF (p = 0.1112) or CRP (p = 0.0534) concentrations, but higher CRP-levels in urine from dogs with cystitis were found compared to dogs without signs of cystitis. From these data we conclude that neither CRP nor NGF in urine or serum can be considered as reliable biomarkers for micturition disorders in dogs with spinal cord disorders in a clinical setting, but their production might be part of the pathogenesis of such disorders. Significantly higher levels of CRP could be found in the urine of dogs with micturition dysfunctions compared to control dogs. This phenomenon could potentially be explained by unspecific extrahepatic CRP production by smooth muscle cells in the dilated bladder.

Herpes zoster with dysfunction of bladder and anus.

PubMed

Jellinek, E H; Tulloch, W S

1976-12-04

Herpes zoster may give rise to dysfunction of bladder and anus. Mucosal lesions have been reported, and 7 cases are described with retention, loss of sensation, or incontinence. Sacral shingles is associated with sensory loss and flaccid detrusor paralysis. Lumbar shingles may cause retention, and zoster at higher levels can also damage the spinal cord. Recovery is usually complete. The implication for schemes of bladder innervation is discussed.

Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury.

PubMed

Kabu, Shushi; Gao, Yue; Kwon, Brian K; Labhasetwar, Vinod

2015-12-10

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. Copyright © 2015 Elsevier B.V. All rights reserved.

Spinal cord injury and women's sexual life: case-control study.

PubMed

Merghati-Khoei, E; Emami-Razavi, S H; Bakhtiyari, M; Lamyian, M; Hajmirzaei, S; Ton-Tab Haghighi, S; Korte, J E; Maasoumi, R

2017-03-01

Study design :This is a case-control study. The objective of this study was to estimate the magnitude of association between spinal cord injury (SCI) and women's quality of sexual life and sexual function. This study was conducted in the Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran. From the referral university-based clinics, we used simple random sampling to recruit 62 women: 31 women with SCI and 31 women without SCI. Socio-demographic and reproductive traits questionnaire, Sexual Quality of life-Female (SQOL-F), Female Sexual Function Index (FSFI) and Spinal Cord Independence Measure (SCIM) were completed using telephone and face-to-face interviews in the cases and controls. After univariate analyses, multivariate linear and proportional odds regression models were conducted to investigate the relation between SCI and women's quality of sexual life, as well as sexual function. The mean age of cases and controls was 35.42±6.51 and 33.77±4.02 years. Most women were high school-educated and housewives. Adjusting for probable confounders, the proportional odds regression model showed a significant relationship between the spinal cord injury (AOR=4.2, 95% CI: 1.8-9.2), non-college-educated (AOR=3.1, 95% CI: 1.2-5.9) and employed (AOR=1.8, 95% CI: 1.1-1.8) variables and being in one of the moderate or poor quality of life classes. Scores of SQOL-F and FSFI domains, except satisfaction, were significantly worse in cases versus controls (P<0.001). Although our participants showed low sexual dysfunction, they tended to report moderate to poor quality of sexual life. Our findings support the implication that sexual rehabilitation must be provided for women with SCI soon after injury.

Human Glial-Restricted Progenitor Transplantation into Cervical Spinal Cord of the SOD1G93A Mouse Model of ALS

PubMed Central

Lepore, Angelo C.; O'Donnell, John; Kim, Andrew S.; Williams, Timothy; Tuteja, Alicia; Rao, Mahendra S.; Kelley, Linda L.; Campanelli, James T.; Maragakis, Nicholas J.

2011-01-01

Cellular abnormalities are not limited to motor neurons in amyotrophic lateral sclerosis (ALS). There are numerous observations of astrocyte dysfunction in both humans with ALS and in SOD1G93A rodents, a widely studied ALS model. The present study therapeutically targeted astrocyte replacement in this model via transplantation of human Glial-Restricted Progenitors (hGRPs), lineage-restricted progenitors derived from human fetal neural tissue. Our previous findings demonstrated that transplantation of rodent-derived GRPs into cervical spinal cord ventral gray matter (in order to target therapy to diaphragmatic function) resulted in therapeutic efficacy in the SOD1G93A rat. Those findings demonstrated the feasibility and efficacy of transplantation-based astrocyte replacement for ALS, and also show that targeted multi-segmental cell delivery to cervical spinal cord is a promising therapeutic strategy, particularly because of its relevance to addressing respiratory compromise associated with ALS. The present study investigated the safety and in vivo survival, distribution, differentiation, and potential efficacy of hGRPs in the SOD1G93A mouse. hGRP transplants robustly survived and migrated in both gray and white matter and differentiated into astrocytes in SOD1G93A mice spinal cord, despite ongoing disease progression. However, cervical spinal cord transplants did not result in motor neuron protection or any therapeutic benefits on functional outcome measures. This study provides an in vivo characterization of this glial progenitor cell and provides a foundation for understanding their capacity for survival, integration within host tissues, differentiation into glial subtypes, migration, and lack of toxicity or tumor formation. PMID:21998733

Evaluation of the thoraco-laryngeal reflex ('slap test') as an aid to the diagnosis of cervical spinal cord and brainstem disease in horses.

PubMed

Newton-Clarke, M J; Divers, T J; Delahunta, A; Mohammed, H O

1994-09-01

A study was conducted over a 12 month period to assess the specificity and sensitivity of the 'slap test', using endoscopic evaluation, in the detection of cervical spinal cord and caudal brainstem lesions in horses. Fifteen ataxic horses were subjected to the 'slap test' and subsequently examined post mortem. Twelve out of the 15 had histopathological lesions consistent with their clinical signs. Thirteen horses with no history of neurological dysfunction and no histopathological evidence of cervical spinal cord or brainstem disease were used as controls. The laryngeal adductory responses exhibited by all horses were filmed and later scored independently by 3 assessors. The proportion of animals diagnosed with cervical spinal cord and/or brainstem disease, defined by histopathological criteria, was found to be statistically similar to the proportion with abnormal 'slap test' responses, using the McNemar chi-Square test. Despite statistical significance between proportions, sensitivity of the 'slap test' was low, 50% for the left side on both days and 58% for the right side. Specificity was higher, 69% (Day 1) and 75% (Day 2) for the left side and 75% (Day 1) and 69% (Day 2) for the right side. In contrast to this, conventional neurological examination was found to be 100% sensitive and 81% specific in the detection of lesions of histopathological significance in the cervical spinal cord/caudal brainstem. Agreement between scores for the 'slap test' from the same assessor on different days was good, with values for kappa of 0.59 to 0.85. In contrast, agreement between assessors on the 'slap test' score was poor, with kappa 0.35.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed

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

2010-03-01

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

Infertility in Men with Spinal Cord Injury: Research and Treatment

PubMed Central

Brackett, Nancy L.

2012-01-01

Spinal cord injury (SCI) occurs most often to young men. Following SCI, most men are infertile due to a combination of erectile dysfunction, ejaculatory dysfunction and semen abnormalities. Erectile dysfunction may be treated by the same therapies that are used in the general population. Similarly, the same treatments that are effective to assist conception in couples with non-SCI male factor patients are effective in assisting conception in SCI male-factor patients. The most apparent differences in male-factor symptoms between SCI and non-SCI patients are the high occurrences of anejaculation and atypical semen profiles in men with SCI. Methods available to assist ejaculation in men with SCI include penile vibratory stimulation and EEJ. Use of surgical sperm retrieval as the first line of treatment for anejaculation in men with SCI is controversial. Most men with SCI have a unique semen profile characterized by normal sperm concentration, but abnormally low sperm motility. Toxic substances in the semen contribute to this problem. Despite impaired sperm parameters, pregnancy outcomes using sperm from men with SCI are similar to pregnancy outcomes using sperm from non-SCI men. Future studies should focus on improving natural ejaculation and improving semen quality in these men. PMID:24278717

Dietary omega-3 polyunsaturated fatty acids improve the neurolipidome and restore the DHA status while promoting functional recovery after experimental spinal cord injury.

PubMed

Figueroa, Johnny D; Cordero, Kathia; Llán, Miguel S; De Leon, Marino

2013-05-15

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) confer multiple health benefits and decrease the risk of neurological disorders. Studies are needed, however, to identify promising cellular targets and to assess their prophylactic value against neurodegeneration. The present study (1) examined the efficacy of a preventive diet enriched with ω-3 PUFAs to reduce dysfunction in a well-established spinal cord injury (SCI) animal model and (2) used a novel metabolomics data analysis to identify potential neurolipidomic targets. Rats were fed with either control chow or chow enriched with ω-3 PUFAs (750 mg/kg/day) for 8 weeks before being subjected to a sham or a contusion SCI operation. We report new evidence showing that rats subjected to SCI after being pre-treated with a diet enriched with ω-3 PUFAs exhibit significantly better functional outcomes. Pre-treated animals exhibited lower sensory deficits, autonomic bladder recovery, and early improvements in locomotion that persisted for at least 8 weeks after trauma. We found that SCI triggers a robust alteration in the cord PUFA neurolipidome, which was characterized by a marked docosahexaenoic acid (DHA) deficiency. This DHA deficiency was associated with dysfunction and corrected with the ω-3 PUFA-enriched diet. Multivariate data analyses revealed that the spinal cord of animals consuming the ω-3 PUFA-enriched diet had a fundamentally distinct neurolipidome, particularly increasing the levels of essential and long chain ω-3 fatty acids and lysolipids at the expense of ω-6 fatty acids and its metabolites. Altogether, dietary ω-3 PUFAs prophylaxis confers resiliency to SCI mediated, at least in part, by generating a neuroprotective and restorative neurolipidome.

Dietary Omega-3 Polyunsaturated Fatty Acids Improve the Neurolipidome and Restore the DHA Status while Promoting Functional Recovery after Experimental Spinal Cord Injury

PubMed Central

Figueroa, Johnny D.; Cordero, Kathia; llán, Miguel S.

2013-01-01

Abstract Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) confer multiple health benefits and decrease the risk of neurological disorders. Studies are needed, however, to identify promising cellular targets and to assess their prophylactic value against neurodegeneration. The present study (1) examined the efficacy of a preventive diet enriched with ω-3 PUFAs to reduce dysfunction in a well-established spinal cord injury (SCI) animal model and (2) used a novel metabolomics data analysis to identify potential neurolipidomic targets. Rats were fed with either control chow or chow enriched with ω-3 PUFAs (750 mg/kg/day) for 8 weeks before being subjected to a sham or a contusion SCI operation. We report new evidence showing that rats subjected to SCI after being pre-treated with a diet enriched with ω-3 PUFAs exhibit significantly better functional outcomes. Pre-treated animals exhibited lower sensory deficits, autonomic bladder recovery, and early improvements in locomotion that persisted for at least 8 weeks after trauma. We found that SCI triggers a robust alteration in the cord PUFA neurolipidome, which was characterized by a marked docosahexaenoic acid (DHA) deficiency. This DHA deficiency was associated with dysfunction and corrected with the ω-3 PUFA-enriched diet. Multivariate data analyses revealed that the spinal cord of animals consuming the ω-3 PUFA-enriched diet had a fundamentally distinct neurolipidome, particularly increasing the levels of essential and long chain ω-3 fatty acids and lysolipids at the expense of ω-6 fatty acids and its metabolites. Altogether, dietary ω-3 PUFAs prophylaxis confers resiliency to SCI mediated, at least in part, by generating a neuroprotective and restorative neurolipidome. PMID:23294084

Intraperitoneally administered IgG from patients with amyotrophic lateral sclerosis or from an immune-mediated goat model increase the levels of TNF-α, IL-6, and IL-10 in the spinal cord and serum of mice.

PubMed

Obál, Izabella; Klausz, Gergely; Mándi, Yvette; Deli, Mária; Siklós, László; Engelhardt, József I

2016-05-24

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that involves the selective loss of the upper and lower motor neurons (MNs). Neuroinflammation has been implicated in the pathogenesis of the sporadic form of the disease. We earlier developed immune-mediated animal models of ALS and demonstrated humoral and cellular immune reactions in the nervous system and in the sera of patients and animals. The accumulation of immunoglobulin G (IgG), an elevated intracellular level of calcium, ultrastructural alterations in the MNs, and activation of the microglia were noted in the spinal cord of ALS patients. Similar alterations developed in mice inoculated intraperitoneally with IgG from ALS patients or from an immune-mediated goat model. We have now examined whether the intraperitoneal injection of mice with IgG from sporadic ALS patients or from immunized goats with the homogenate of the anterior horn of the bovine spinal cord is associated with changes in the pro-inflammatory (TNF-α and IL-6) and anti-inflammatory (IL-10) cytokines in the spinal cord and serum of the mice. The levels of cytokines were measured by ELISA. Intraperitoneally administered IgG from the ALS patients induced subclinical signs of MN disease, while the injection of IgG from immunized goats resulted in a severe respiratory dysfunction and limb paralysis 24 h after the injections. Significantly increased levels of TNF-α and IL-10 were detected in the spinal cord of the mice injected with the human ALS IgG. The level of IL-6 increased primarily in the serum. The IgG from the immunized goats induced highly significant increases in the levels of all three cytokines in the serum and the spinal cord of mice. Our earlier experiments had proved that when ALS IgG or IgG from immune-mediated animal models was inoculated into mice, it was taken up in the MNs and had the ability to initiate damage in them. The pathological process was paralleled by microglia recruitment and activation in the spinal cord. The present experiment revealed that these forms of IgG cause significant increases in certain cytokine levels locally in the spinal cord and in the serum of the inoculated mice. These results suggest that IgG directed to the MNs may be an initial element in the damage to the MNs both in human ALS and in its immune-mediated animal models.

Tethered Spinal Cord Syndrome

MedlinePlus

... the spinal cord. These attachments cause an abnormal stretching of the spinal cord. The course of the ... the spinal cord. These attachments cause an abnormal stretching of the spinal cord. The course of the ...

Inherited neuroaxonal dystrophy in dogs causing lethal, fetal-onset motor system dysfunction and cerebellar hypoplasia

PubMed Central

Fyfe, John C.; Al-Tamimi, Raba' A.; Castellani, Rudy J.; Rosenstein, Diana; Goldowitz, Daniel; Henthorn, Paula S.

2010-01-01

Neuroaxonal dystrophy in brainstem, spinal cord tracts, and spinal nerves accompanied by cerebellar hypoplasia was observed in a colony of laboratory dogs. Fetal akinesia was documented by ultrasonographic examination. At birth, affected puppies exhibited stereotypical positioning of limbs, scoliosis, arthrogryposis, pulmonary hypoplasia, and respiratory failure. Regional hypoplasia in the central nervous system was apparent grossly, most strikingly as underdeveloped cerebellum and spinal cord. Histopathologic abnormalities included swollen axons and spheroids in brainstem and spinal cord tracts; reduced cerebellar foliation, patchy loss of Purkinje cells, multifocal thinning of the external granular cell layer, and loss of neurons in the deep cerebellar nuclei; spheroids and loss of myelinated axons in spinal roots and peripheral nerves; increased myocyte apoptosis in skeletal muscle; and fibrofatty connective tissue proliferation around joints. Breeding studies demonstrated that the canine disorder is a fully penetrant, simple autosomal recessive trait. The disorder demonstrated a type and distribution of lesions homologous to that of human infantile neuroaxonal dystrophy (INAD), most commonly caused by mutations of PLA2G6, but alleles of informative markers flanking the canine PLA2G6 locus did not associate with the canine disorder. Thus, fetal-onset neuroaxonal dystrophy in dogs, a species with well-developed genome mapping resources, provides a unique opportunity for additional disease gene discovery and understanding of this pathology. PMID:20653033

Effect of spinal monoaminergic neuronal system dysfunction on pain threshold in rats, and the analgesic effect of serotonin and norepinephrine reuptake inhibitors.

PubMed

Tamano, Ryuta; Ishida, Mitsuhiro; Asaki, Toshiyuki; Hasegawa, Minoru; Shinohara, Shunji

2016-02-26

Dysfunction in the central serotonin (5-HT) and norepinephrine (NE) systems cause depression and pain. Descending spinal pain modulatory pathways are important in the analgesic mechanisms of antidepressants, particularly serotonin and norepinephrine reuptake inhibitors (SNRIs). While many non-clinical studies have demonstrated the roles of central monoaminergic systems in pain, there is little evidence to illuminate the direct contribution of spinal descending pain modulatory systems independently of depressive-like behavior. To examine the effects of dysfunction of spinal monoaminergic systems on pain sensitivity, we established a rat chronic pain model by administering lumbar-intrathecal reserpine to minimize its influence on brain. Lumbar-intrathecal reserpine evoked persistent mechanical hypersensitivity and corresponding reductions in spinal 5-HT and NE concentrations (from 767.2 to 241.6ng/g and from 455.9 to 41.7ng/g, respectively after reserpine 30nmol). Lumbar-intrathecal reserpine did not deplete brain monoamines or bring about depressive-like behavior in the forced swim test. Spinal monoamines depletion-induced pain sensitivity was ameliorated by lumbar-intrathecal administration of the SNRIs (duloxetine and milnacipran) in dose-dependent manners. These suggest that increased pain sensitivity could be induced by dysfunction solely of the descending pain modulatory system, regardless of depressive-like behavior, and lumbar-intrathecal administration of SNRIs could ameliorate the pain sensitivity which might be mediated by affecting the descending pain modulatory system in the spinal cord, not via their antidepressant effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Concepts on the pathogenesis of adolescent idiopathic scoliosis. Bone growth and mass, vertebral column, spinal cord, brain, skull, extra-spinal left-right skeletal length asymmetries, disproportions and molecular pathogenesis.

PubMed

Burwell, R Geoffrey; Dangerfield, Peter H; Freeman, Brian J C

2008-01-01

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). Encouraging advances thought to be related to AIS pathogenesis have recently been made in several fields including anthropometry of bone growth, bone mass, spinal growth modulation, extra-spinal left-right skeletal length asymmetries and disproportions, magnetic resonance imaging of vertebral column, spinal cord, brain, skull, and molecular pathogenesis. These advances are leading to the evaluation of new treatments including attempts at minimally invasive surgery on the spine and peri-apical ribs. Several concepts of AIS are outlined indicating their clinical applications but not their research potential. The concepts, by derivation morphological, molecular and mathematical, are addressed in 15 sections: 1) initiating and progressive factors; 2) relative anterior spinal overgrowth; 3) dorsal shear forces that create axial rotational instability; 4) rotational preconstraint; 5) uncoupled, or asynchronous, spinal neuro-osseous growth; 6) brain, nervous system and skull; 7) a novel neuro-osseous escalator concept based on a putative abnormality of two normal polarized processes namely, a) increasing skeletal dimensions, and b) the CNS body schema - both contained within a neuro-osseous timing of maturation (NOTOM) concept; 8) transverse plane pelvic rotation, skeletal asymmetries and developmental theory; 9) thoraco-spinal concept; 10) origin in contracture at the hips; 11) osteopenia; 12) melatonin deficiency; 13) systemic melatonin-signaling pathway dysfunction; 14) platelet calmodulin dysfunction; and 15) biomechanical spinal growth modulation. From these concepts, a collective model for AIS pathogenesis is formulated. The central concept of this model includes the body schema of the neural systems, widely-studied in adults, that control normal posture and coordinated movements with frames of reference in the posterior parietal cortex. The escalator concept has implications for the normal development of upright posture, and the evolution in humans of neural control, the trunk and unique bipedal gait.

N-methyl-D-aspartate receptor antagonist MK-801 prevents apoptosis in rats that have undergone fetal spinal cord transplantation following spinal hemisection.

PubMed

Zhang, Qiang; Shao, Yang; Zhao, Changsong; Cai, Juan; Sun, Sheng

2014-12-01

Spinal cord injury is the main cause of paraplegia, but effective therapies for it are lacking. Embryonic spinal cord transplantation is able to repair spinal cord injury, albeit with a large amount of neuronal apoptosis remaining in the spinal cord. MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, is able to reduce cell death by decreasing the concentration of excitatory amino acids and preventing extracellular calcium ion influx. In this study, the effect of MK-801 on the apoptosis of spinal cord neurons in rats that have received a fetal spinal cord (FSC) transplant following spinal hemisection was investigated. Wistar rats were divided into three groups: Spinal cord hemisection injury with a combination of FSC transplantation and MK-801 treatment (group A); spinal cord hemisection injury with FSC transplantation (group B); and spinal cord injury with insertion of a Gelfoam pledget (group C). The rats were sacrificed 1, 3, 7 and 14 days after the surgery. Apoptosis in spinal slices from the injured spinal cord was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling reaction, and the expression of B-cell lymphoma-2 (Bcl-2) was measured by immunohistochemistry. The positive cells were quantitatively analyzed using a computer image analysis system. The rate of apoptosis and the positive expression of Bcl-2 protein in the spinal cord neurons in the three groups decreased in the following order: C>B>A (P<0.05) and A>B>C (P<0.05), respectively. This indicates that treatment with the NMDA receptor antagonist MK-801 prevents apoptosis in the spinal cord neurons of rats that have undergone FSC transplantation following spinal hemisection.

N-methyl-D-aspartate receptor antagonist MK-801 prevents apoptosis in rats that have undergone fetal spinal cord transplantation following spinal hemisection

PubMed Central

ZHANG, QIANG; SHAO, YANG; ZHAO, CHANGSONG; CAI, JUAN; SUN, SHENG

2014-01-01

Spinal cord injury is the main cause of paraplegia, but effective therapies for it are lacking. Embryonic spinal cord transplantation is able to repair spinal cord injury, albeit with a large amount of neuronal apoptosis remaining in the spinal cord. MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, is able to reduce cell death by decreasing the concentration of excitatory amino acids and preventing extracellular calcium ion influx. In this study, the effect of MK-801 on the apoptosis of spinal cord neurons in rats that have received a fetal spinal cord (FSC) transplant following spinal hemisection was investigated. Wistar rats were divided into three groups: Spinal cord hemisection injury with a combination of FSC transplantation and MK-801 treatment (group A); spinal cord hemisection injury with FSC transplantation (group B); and spinal cord injury with insertion of a Gelfoam pledget (group C). The rats were sacrificed 1, 3, 7 and 14 days after the surgery. Apoptosis in spinal slices from the injured spinal cord was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling reaction, and the expression of B-cell lymphoma-2 (Bcl-2) was measured by immunohistochemistry. The positive cells were quantitatively analyzed using a computer image analysis system. The rate of apoptosis and the positive expression of Bcl-2 protein in the spinal cord neurons in the three groups decreased in the following order: C>B>A (P<0.05) and A>B>C (P<0.05), respectively. This indicates that treatment with the NMDA receptor antagonist MK-801 prevents apoptosis in the spinal cord neurons of rats that have undergone FSC transplantation following spinal hemisection. PMID:25371724

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

PubMed

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

2006-02-15

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

Evaluation of an Acute RNAi-Mediated Therapeutic for Visual Dysfunction Associated with Traumatic Brain Injury

DTIC Science & Technology

2013-10-01

requiring pacemaker  Refusal of consent - Claustrophobia  Spinal Cord Injury  Unstable due to tracheal stenosis and lobar collapse  2 patients had...be stopped.  Heart Block necessitating pacemaker  Unstable from a respiratory point of view due to previous Left lower lobectomy, right upper

21 CFR 882.5880 - Implanted spinal cord stimulator for pain relief.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Implanted spinal cord stimulator for pain relief. (a) Identification. An implanted spinal cord stimulator for pain relief is a device that is used to stimulate electrically a patient's spinal cord to relieve... on the patient's spinal cord and an external transmitter for transmitting the stimulating pulses...

Mitochondrial-Based Therapeutics for the Treatment of Spinal Cord Injury: Mitochondrial Biogenesis as a Potential Pharmacological Target

PubMed Central

Scholpa, Natalie E.

2017-01-01

Spinal cord injury (SCI) is characterized by an initial trauma followed by a progressive cascade of damage referred to as secondary injury. A hallmark of secondary injury is vascular disruption leading to vasoconstriction and decreased oxygen delivery, which directly reduces the ability of mitochondria to maintain homeostasis and leads to loss of ATP-dependent cellular functions, calcium overload, excitotoxicity, and oxidative stress, further exacerbating injury. Restoration of mitochondria dysfunction during the acute phases of secondary injury after SCI represents a potentially effective therapeutic strategy. This review discusses the past and present pharmacological options for the treatment of SCI as well as current research on mitochondria-targeted approaches. Increased antioxidant activity, inhibition of the mitochondrial permeability transition, alternate energy sources, and manipulation of mitochondrial morphology are among the strategies under investigation. Unfortunately, many of these tactics address single aspects of mitochondrial dysfunction, ultimately proving largely ineffective. Therefore, this review also examines the unexplored therapeutic efficacy of pharmacological enhancement of mitochondrial biogenesis, which has the potential to more comprehensively improve mitochondrial function after SCI. PMID:28935700

Mitochondrial-Based Therapeutics for the Treatment of Spinal Cord Injury: Mitochondrial Biogenesis as a Potential Pharmacological Target.

PubMed

Scholpa, Natalie E; Schnellmann, Rick G

2017-12-01

Spinal cord injury (SCI) is characterized by an initial trauma followed by a progressive cascade of damage referred to as secondary injury. A hallmark of secondary injury is vascular disruption leading to vasoconstriction and decreased oxygen delivery, which directly reduces the ability of mitochondria to maintain homeostasis and leads to loss of ATP-dependent cellular functions, calcium overload, excitotoxicity, and oxidative stress, further exacerbating injury. Restoration of mitochondria dysfunction during the acute phases of secondary injury after SCI represents a potentially effective therapeutic strategy. This review discusses the past and present pharmacological options for the treatment of SCI as well as current research on mitochondria-targeted approaches. Increased antioxidant activity, inhibition of the mitochondrial permeability transition, alternate energy sources, and manipulation of mitochondrial morphology are among the strategies under investigation. Unfortunately, many of these tactics address single aspects of mitochondrial dysfunction, ultimately proving largely ineffective. Therefore, this review also examines the unexplored therapeutic efficacy of pharmacological enhancement of mitochondrial biogenesis, which has the potential to more comprehensively improve mitochondrial function after SCI. U.S. Government work not protected by U.S. copyright.

Urinary tract infections in patients with spinal cord injuries.

PubMed

D'Hondt, Frederiek; Everaert, Karel

2011-12-01

Spinal cord injuries (SCI) result in different lower urinary tract dysfunctions. Because of both the disease and the bladder drainage method, urinary tract infections (UTIs) are one of the most frequent conditions seen in SCI patients. Diagnosis is not always easy due to lack of symptoms. Asymptomatic bacteriuria needs no treatment. If symptoms occur, antibiotherapy is indicated. Duration depends mainly on severity of illness and upper urinary tract or prostatic involvement. Choice of antibiotherapy should be based on local resistance profiles, but fluoroquinolones seems to be an adequate empirical treatment. Prevention of UTI is important, as lots of complications can be foreseen. Catheter care, permanent low bladder pressure and clean intermittent catheterization (CIC) with hydrophilic catheters are interventions that can prevent UTI. Probiotics might be useful, but data are limited.

Early spinal cord and brainstem involvement in infantile Leigh syndrome possibly caused by a novel variant.

PubMed

Tenney, Jeffrey R; Prada, Carlos E; Hopkin, Robert J; Hallinan, Barbara E

2013-12-01

Leigh syndrome, due to a dysfunction of mitochondrial energy metabolism, is a genetically heterogeneous and progressive neurologic disorder that usually occurs in infancy and childhood. Its clinical presentation and neuroimaging findings can be variable, especially early in the course of the disease. This report presents a patient with infantile Leigh syndrome who had atypical radiologic findings on serial neuroimaging studies with early and severe involvement of the cervical spinal cord and brainstem and injury to the thalami and basal ganglia occurring only late in the clinical course. Postmortem microscopic examination supported this timing of injury within the central nervous system. In addition, mitochondrial deoxyribonucleic acid sequencing showed a novel homoplasmic variant that could be responsible for this unique lethal form of Leigh syndrome.

A Clinical Practice Guideline for the Management of Degenerative Cervical Myelopathy: Introduction, Rationale, and Scope.

PubMed

Fehlings, Michael G; Tetreault, Lindsay A; Riew, K Daniel; Middleton, James W; Wang, Jeffrey C

2017-09-01

Degenerative cervical myelopathy (DCM) is a progressive spine disease and the most common cause of spinal cord dysfunction in adults worldwide. Patients with DCM may present with common signs and symptoms of neurological dysfunction, such as paresthesia, abnormal gait, decreased hand dexterity, hyperreflexia, increased tone, and sensory dysfunction. Clinicians across several specialties encounter patients with DCM, including primary care physicians, rehabilitation specialists, therapists, rheumatologists, neurologists, and spinal surgeons. Currently, there are no guidelines that outline how to best manage patients with mild (defined as a modified Japanese Orthopedic Association (mJOA) score of 15-17), moderate (mJOA = 12-14), or severe (mJOA ≤ 11) myelopathy, or nonmyelopathic patients with evidence of cord compression. This guideline provides evidence-based recommendations to specify appropriate treatment strategies for these populations. The intent of our recommendations is to (1) help identify patients at high risk of neurological deterioration, (2) define the role of nonoperative and operative management in each patient population, and (3) determine which patients are most likely to benefit from surgical intervention. The ultimate goal of these guidelines is to improve outcomes and reduce morbidity in patients with DCM by promoting standardization of care and encouraging clinicians to make evidence-informed decisions.

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

DTIC Science & Technology

2015-10-01

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

Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case with distinct MRI findings.

PubMed

Uluc, Kayihan; Baskan, Ozdil; Yildirim, Kadriye Agan; Ozsahin, Selda; Koseoglu, Mesrure; Isak, Baris; Scheper, G C; Gunal, Dilek Ince; van der Knaap, M S

2008-10-15

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a recently described disorder with autosomal recessive mode of inheritance. Lately, mutations in the DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase, have been found as the underlying defect. We report a 19-year-old male patient with cerebellar, pyramidal and dorsal column dysfunctions and specific magnetic resonance imaging (MRI) and characteristic magnetic resonance spectroscopy (MRS) abnormalities. The patient was compound-heterozygous for two mutations in DARS2. MRI showed selective involvement of cerebral and cerebellar white matter and superior and inferior cerebellar peduncles, without contrast enhancement. The U-fibers were spared. The sensory and the pyramidal tracts were affected over their entire length. Involvement of the intraparenchymal trajectories of the trigeminal nerves and mesencephalic trigeminal tracts was demonstrated. In the spinal cord, signal abnormalities were identified in the dorsal columns and the lateral corticospinal tracts. Proton-MRS of the frontal and cerebellar white matter showed elevated lactate, reduced N-acetylaspartate, increased myoinositol and mildly elevated choline. In LBSL, distinct MRI findings should lead to the diagnosis, which can be confirmed by the analysis of the disease gene DARS2.

Therapeutic Hypothermia in Spinal Cord Injury: The Status of Its Use and Open Questions.

PubMed

Wang, Jiaqiong; Pearse, Damien D

2015-07-24

Spinal cord injury (SCI) is a major health problem and is associated with a diversity of neurological symptoms. Pathophysiologically, dysfunction after SCI results from the culmination of tissue damage produced both by the primary insult and a range of secondary injury mechanisms. The application of hypothermia has been demonstrated to be neuroprotective after SCI in both experimental and human studies. The myriad of protective mechanisms of hypothermia include the slowing down of metabolism, decreasing free radical generation, inhibiting excitotoxicity and apoptosis, ameliorating inflammation, preserving the blood spinal cord barrier, inhibiting astrogliosis, promoting angiogenesis, as well as decreasing axonal damage and encouraging neurogenesis. Hypothermia has also been combined with other interventions, such as antioxidants, anesthetics, alkalinization and cell transplantation for additional benefit. Although a large body of work has reported on the effectiveness of hypothermia as a neuroprotective approach after SCI and its application has been translated to the clinic, a number of questions still remain regarding its use, including the identification of hypothermia's therapeutic window, optimal duration and the most appropriate rewarming rate. In addition, it is necessary to investigate the neuroprotective effect of combining therapeutic hypothermia with other treatment strategies for putative synergies, particularly those involving neurorepair.

Neurogenic bowel management after spinal cord injury: Malaysian experience.

PubMed

Engkasan, Julia Patrick; Sudin, Siti Suhaida

2013-02-01

To describe the bowel programmes utilized by individuals with spinal cord injury; and to determine the association between the outcome of the bowel programmes and various interventions to facilitate defecation. A cross-sectional study. Individuals with spinal cord injury who have neurogenic bowel dysfunction. Face-to-face interviews were conducted using a self-constructed questionnaire that consisted of: (i) demographic and clinical characteristics of the participants; (ii) interventions to facilitate defecation; (iii) bowel care practices; (iv) outcome of the bowel programme (incidence of incontinence and duration of the evacuation procedure); and (v) participant satisfaction with their bowel programme. The majority (79.2%) of subjects used multiple interventions for bowel care. Duration of the evacuation procedure was more than 60 min in 28.0% of participants. Water intake of more than 2 l/day was associated with longer duration of bowel care. Only 8.0% of participants had at least one episode of incontinence per month. The majority of participants (84.8%) were satisfied with their bowel programme. Patients used multiple interventions to manage their bowels and spent a substantial amount of time performing bowel care. Nevertheless, the incidence of incontinence was low and satisfaction with their bowel programme was high.

Thrombospondin-1 modified bone marrow mesenchymal stem cells (BMSCs) promote neurite outgrowth and functional recovery in rats with spinal cord injury

PubMed Central

Pu, Yujie; Meng, Ke; Gu, Chuanlong; Wang, Linlin; Zhang, Xiaoming

2017-01-01

Stem cell therapies are currently gaining momentum in the treatment of spinal cord injury (SCI). However, unsatisfied intrinsic neurite growth capacity constitutes significant obstacles for injured spinal cord repair and ultimately results in neurological dysfunction. The present study assessed the efficacy of thrombospondin-1 (TSP-1), a neurite outgrowth-promoting molecule, modified bone marrow mesenchymal stem cells (BMSCs) on promoting neurite outgrowth in vitro and in vivo of Oxygen–Glucose Deprivation (OGD) treated motor neurons and SCI rat models. The present results demonstrated that the treatment of BMSCs+TSP-1 could promote the neurite length, neuronal survival, and functional recovery after SCI. Additionally, TSP-1 could activate transforming growth factor-β1 (TGF-β1) then induced the smad2 phosphorylation, and expedited the expression of GAP-43 to promote neurite outgrowth. The present study for the first time demonstrated that BMSCs+TSP-1 could promote neurite outgrowth and functional recovery after SCI partly through the TGF-β1/p-Samd2 pathway. The study provided a novel encouraging evidence for the potential treatment of BMSCs modification with TSP-1 in patients with SCI. PMID:29221205

Dendritic spine remodeling following early and late Rac1 inhibition after spinal cord injury: evidence for a pain biomarker

PubMed Central

Zhao, Peng; Hill, Myriam; Liu, Shujun; Chen, Lubin; Bangalore, Lakshmi; Waxman, Stephen G.

2016-01-01

Neuropathic pain is a significant complication following spinal cord injury (SCI) with few effective treatments. Drug development for neuropathic pain often fails because preclinical studies do not always translate well to clinical conditions. Identification of biological characteristics predictive of disease state or drug responsiveness could facilitate more effective clinical translation. Emerging evidence indicates a strong correlation between dendritic spine dysgenesis and neuropathic pain. Because dendritic spines are located on dorsal horn neurons within the spinal cord nociceptive system, dendritic spine remodeling provides a unique opportunity to understand sensory dysfunction after SCI. In this study, we provide support for the postulate that dendritic spine profiles can serve as biomarkers for neuropathic pain. We show that dendritic spine profiles after SCI change to a dysgenic state that is characteristic of neuropathic pain in a Rac1-dependent manner. Suppression of the dysgenic state through inhibition of Rac1 activity is accompanied by attenuation of neuropathic pain. Both dendritic spine dysgenesis and neuropathic pain return when inhibition of Rac1 activity is lifted. These findings suggest the utility of dendritic spines as structural biomarkers for neuropathic pain. PMID:26936986

A Toll-Like Receptor 9 Antagonist Improves Bladder Function and White Matter Sparing in Spinal Cord Injury

PubMed Central

David, Brian T.; Sampath, Sujitha; Dong, Wei; Heiman, Adee; Rella, Courtney E.; Elkabes, Stella

2014-01-01

Abstract Spinal cord injury (SCI) affects motor, sensory, and autonomic functions. As current therapies do not adequately alleviate functional deficits, the development of new and more effective approaches is of critical importance. Our earlier investigations indicated that intrathecal administration of a toll-like receptor 9 (TLR9) antagonist, cytidine-phosphate-guanosine oligodeoxynucleotide 2088 (CpG ODN 2088), to mice sustaining a severe, mid-thoracic contusion injury diminished neuropathic pain but did not alter locomotor deficits. These changes were paralleled by a decrease in the pro-inflammatory response at the injury epicenter. Using the same SCI paradigm and treatment regimen, the current studies investigated the effects of the TLR9 antagonist on bladder function. We report that the TLR9 antagonist decreases SCI-elicited urinary retention and ameliorates bladder morphopathology without affecting kidney function. A significant improvement in white matter sparing was also observed, most likely due to alterations in the inflammatory milieu. These findings indicate that the TLR9 antagonist has beneficial effects not only in reducing sensory deficits, but also on bladder dysfunction and tissue preservation. Thus, modulation of innate immune receptor signaling in the spinal cord can impact the effects of SCI. PMID:24936867

A toll-like receptor 9 antagonist improves bladder function and white matter sparing in spinal cord injury.

PubMed

David, Brian T; Sampath, Sujitha; Dong, Wei; Heiman, Adee; Rella, Courtney E; Elkabes, Stella; Heary, Robert F

2014-11-01

Spinal cord injury (SCI) affects motor, sensory, and autonomic functions. As current therapies do not adequately alleviate functional deficits, the development of new and more effective approaches is of critical importance. Our earlier investigations indicated that intrathecal administration of a toll-like receptor 9 (TLR9) antagonist, cytidine-phosphate-guanosine oligodeoxynucleotide 2088 (CpG ODN 2088), to mice sustaining a severe, mid-thoracic contusion injury diminished neuropathic pain but did not alter locomotor deficits. These changes were paralleled by a decrease in the pro-inflammatory response at the injury epicenter. Using the same SCI paradigm and treatment regimen, the current studies investigated the effects of the TLR9 antagonist on bladder function. We report that the TLR9 antagonist decreases SCI-elicited urinary retention and ameliorates bladder morphopathology without affecting kidney function. A significant improvement in white matter sparing was also observed, most likely due to alterations in the inflammatory milieu. These findings indicate that the TLR9 antagonist has beneficial effects not only in reducing sensory deficits, but also on bladder dysfunction and tissue preservation. Thus, modulation of innate immune receptor signaling in the spinal cord can impact the effects of SCI.

Thiazide use is associated with reduced risk for incident lower extremity fractures in men with spinal cord injury.

PubMed

Carbone, Laura D; Chin, Amy S; Lee, Todd A; Burns, Stephen P; Svircev, Jelena N; Hoenig, Helen M; Bailey, Lauren; Weaver, Frances M

2014-06-01

To determine the association between thiazide use and lower extremity fractures in patients who are men with a spinal cord injury (SCI). Cohort study from fiscal years 2002 to 2007. Medical centers. Men (N=6969) with an SCI from the Veterans Affairs (VA) Spinal Cord Dysfunction (SCD) Registry, including 1433 users of thiazides and 5536 nonusers of thiazides. Thiazide use versus nonuse. Incident lower extremity fractures. Among the men, 21% in the VA SCD Registry (fiscal years 2002-2007) included in these analyses used thiazide diuretics. There were 832 incident lower extremity fractures over the time period of this study: 110 fractures (7.7%) in 1433 thiazide users and 722 fractures (13%) in 5536 nonusers of thiazides. In unadjusted and adjusted models alike, thiazide use was associated with at least a one-quarter risk reduction in lower extremity fracture at any given point in time (unadjusted: hazard ratio (HR)=.75; 95% confidence interval (CI), .59-.94; adjusted: HR=.74; 95% CI, .58-.95). Thiazide use is common in men with SCI and is associated with a decreased likelihood for lower extremity fractures. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2013-10-01

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

Somatic genital reflexes in rats with a nod to humans: anatomy, physiology, and the role of the social neuropeptides

PubMed Central

Normandin, Joseph J.; Murphy, Anne Z.

2011-01-01

Somatic genital reflexes such as ejaculation and vaginocervical contractions are produced through the striated muscles associated with the genitalia. The coordination of these reflexes is surprisingly complex and involves a number of lumbosacral spinal and supraspinal systems. The rat model has proved to be an excellent source of information regarding these mechanisms, and many parallels to research in humans can be drawn. An understanding of the spinal systems involving the lumbosacral spinal cord, both efferent and afferent, has been generated through decades of research. Spinal and supraspinal mechanisms of descending excitation, through a spinal ejaculation generator in the lumbar spinal cord and thalamus, and descending inhibition, through the ventrolateral medulla, have been identified and characterized both anatomically and physiologically. In addition, delineation of the neural circuits whereby ascending genitosensory information regarding the regulation of somatic genital reflexes is relayed supraspinally has also been the topic of recent investigation. Lastly, the importance of the “social neuropeptides” oxytocin and vasopressin in the regulation of somatic genital reflexes, and associated sociosexual behaviors, is emerging. This work not only has implications for understanding how nervous systems generate sexual behavior, but also provides treatment targets for sexual dysfunction in people. PMID:21338605

Testosterone Plus Finasteride Treatment After Spinal Cord Injury

ClinicalTrials.gov

2018-05-16

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

Subpial Adeno-associated Virus 9 (AAV9) Vector Delivery in Adult Mice.

PubMed

Tadokoro, Takahiro; Miyanohara, Atsushi; Navarro, Michael; Kamizato, Kota; Juhas, Stefan; Juhasova, Jana; Marsala, Silvia; Platoshyn, Oleksandr; Curtis, Erik; Gabel, Brandon; Ciacci, Joseph; Lukacova, Nada; Bimbova, Katarina; Marsala, Martin

2017-07-13

The successful development of a subpial adeno-associated virus 9 (AAV9) vector delivery technique in adult rats and pigs has been reported on previously. Using subpially-placed polyethylene catheters (PE-10 or PE-5) for AAV9 delivery, potent transgene expression through the spinal parenchyma (white and gray matter) in subpially-injected spinal segments has been demonstrated. Because of the wide range of transgenic mouse models of neurodegenerative diseases, there is a strong desire for the development of a potent central nervous system (CNS)-targeted vector delivery technique in adult mice. Accordingly, the present study describes the development of a spinal subpial vector delivery device and technique to permit safe and effective spinal AAV9 delivery in adult C57BL/6J mice. In spinally immobilized and anesthetized mice, the pia mater (cervical 1 and lumbar 1-2 spinal segmental level) was incised with a sharp 34 G needle using an XYZ manipulator. A second XYZ manipulator was then used to advance a blunt 36G needle into the lumbar and/or cervical subpial space. The AAV9 vector (3-5 µL; 1.2 x 10 13 genome copies (gc)) encoding green fluorescent protein (GFP) was then injected subpially. After injections, neurological function (motor and sensory) was assessed periodically, and animals were perfusion-fixed 14 days after AAV9 delivery with 4% paraformaldehyde. Analysis of horizontal or transverse spinal cord sections showed transgene expression throughout the entire spinal cord, in both gray and white matter. In addition, intense retrogradely-mediated GFP expression was seen in the descending motor axons and neurons in the motor cortex, nucleus ruber, and formatio reticularis. No neurological dysfunction was noted in any animals. These data show that the subpial vector delivery technique can successfully be used in adult mice, without causing procedure-related spinal cord injury, and is associated with highly potent transgene expression throughout the spinal neuraxis.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-06-01

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

Optical monitoring of spinal cord hemodynamics, a feasibility study

NASA Astrophysics Data System (ADS)

Shadgan, Babak; Kwon, Brian K.; Streijger, Femke; Manouchehri, Neda; So, Kitty; Shortt, Katelyn; Cripton, Peter A.; Macnab, Andrew

2017-02-01

Background: After an acute traumatic spinal cord injury (SCI), the spinal cord is subjected to ischemia, hypoxia, and increased hydrostatic pressure which exacerbate further secondary damage and neuronal deficit. The purpose of this pilot study was to explore the use of near infrared spectroscopy (NIRS) for non-invasive and real-time monitoring of these changes within the injured spinal cord in an animal model. NIRS is a non-invasive optical technique that utilizes light in the near infrared spectrum to monitor changes in the concentration of tissue chromophores from which alterations in tissues oxygenation and perfusion can be inferred in real time. Methods: A custom-made miniaturized NIRS sensor was developed to monitor spinal cord hemodynamics and oxygenation noninvasively and in real time simultaneously with invasive, intraparenchymal monitoring in a pig model of SCI. The spinal cord around the T10 injury site was instrumented with intraparenchymal probes inserted directly into the spinal cord to measure oxygen pressure, blood flow, and hydrostatic pressure, and the same region of the spinal cord was monitored with the custom-designed extradural NIRS probe. We investigated how well the extradural NIRS probe detected intraparenchymal changes adjacent to the injury site after alterations in systemic blood pressure, global hypoxia, and traumatic injury generated by a weight-drop contusion. Results: The NIRS sensor successfully identified periods of systemic hypoxia, re-ventilation and changes in spinal cord perfusion and oxygenation during alterations of mean arterial pressure and following spinal cord injury. Conclusion: This pilot study indicates that extradural NIRS monitoring of the spinal cord is feasible as a non-invasive optical method to identify changes in spinal cord hemodynamics and oxygenation in real time. Further development of this technique would allow clinicians to monitor real-time physiologic changes within the injured spinal cord during the acute post-injury period.

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

PubMed Central

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

2012-01-01

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

International bowel function basic spinal cord injury data set.

PubMed

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

2009-03-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-11-01

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

Neuroprotective Effects of Sulforaphane after Contusive Spinal Cord Injury

PubMed Central

Benedict, Andrea L.; Mountney, Andrea; Hurtado, Andres; Bryan, Kelley E.; Schnaar, Ronald L.; Dinkova-Kostova, Albena T.

2012-01-01

Abstract Traumatic spinal cord injury (SCI) leads to oxidative stress, calcium mobilization, glutamate toxicity, the release of proinflammatory factors, and depletion of reduced glutathione (GSH) at the site of injury. Induction of the Keap1/Nrf2/ARE pathway can alleviate neurotoxicity by protecting against GSH depletion, oxidation, intracellular calcium overload, mitochondrial dysfunction, and excitotoxicity. Sulforaphane (SF), an isothiocyanate derived from broccoli, is a potent naturally-occurring inducer of the Keap1/Nrf2/ARE pathway, leading to upregulation of genes encoding cytoprotective proteins such as NAD(P)H: quinone oxidoreductase 1, and GSH-regulatory enzymes. Additionally, SF can attenuate inflammation by inhibiting the nuclear factor-κB (NF-κB) pathway, and the enzymatic activity of the proinflammatory cytokine macrophage inhibitory factor (MIF). Our study examined systemic administration of SF in a rat model of contusion SCI, in an effort to utilize its indirect antioxidant and anti-inflammatory properties to decrease secondary injury. Two doses of SF (10 or 50 mg/kg) were administered at 10 min and 72 h after contusion SCI. SF (50 mg/kg) treatment resulted in both acute and long-term beneficial effects, including upregulation of the phase 2 antioxidant response at the injury site, decreased mRNA levels of inflammatory cytokines (i.e., MMP-9) in the injured spinal cord, inactivation of urinary MIF tautomerase activity, enhanced hindlimb locomotor function, and an increased number of serotonergic axons caudal to the lesion site. These findings demonstrate that SF provides neuroprotective effects in the spinal cord after injury, and could be a candidate for therapy of SCI. PMID:22853439

Neuroprotective effects of sulforaphane after contusive spinal cord injury.

PubMed

Benedict, Andrea L; Mountney, Andrea; Hurtado, Andres; Bryan, Kelley E; Schnaar, Ronald L; Dinkova-Kostova, Albena T; Talalay, Paul

2012-11-01

Traumatic spinal cord injury (SCI) leads to oxidative stress, calcium mobilization, glutamate toxicity, the release of proinflammatory factors, and depletion of reduced glutathione (GSH) at the site of injury. Induction of the Keap1/Nrf2/ARE pathway can alleviate neurotoxicity by protecting against GSH depletion, oxidation, intracellular calcium overload, mitochondrial dysfunction, and excitotoxicity. Sulforaphane (SF), an isothiocyanate derived from broccoli, is a potent naturally-occurring inducer of the Keap1/Nrf2/ARE pathway, leading to upregulation of genes encoding cytoprotective proteins such as NAD(P)H: quinone oxidoreductase 1, and GSH-regulatory enzymes. Additionally, SF can attenuate inflammation by inhibiting the nuclear factor-κB (NF-κB) pathway, and the enzymatic activity of the proinflammatory cytokine macrophage inhibitory factor (MIF). Our study examined systemic administration of SF in a rat model of contusion SCI, in an effort to utilize its indirect antioxidant and anti-inflammatory properties to decrease secondary injury. Two doses of SF (10 or 50 mg/kg) were administered at 10 min and 72 h after contusion SCI. SF (50 mg/kg) treatment resulted in both acute and long-term beneficial effects, including upregulation of the phase 2 antioxidant response at the injury site, decreased mRNA levels of inflammatory cytokines (i.e., MMP-9) in the injured spinal cord, inactivation of urinary MIF tautomerase activity, enhanced hindlimb locomotor function, and an increased number of serotonergic axons caudal to the lesion site. These findings demonstrate that SF provides neuroprotective effects in the spinal cord after injury, and could be a candidate for therapy of SCI.

Persistent Outpatient Hypertension Is Independently Associated with Spinal Cord Dysfunction and Imaging Characteristics of Spinal Cord Damage among Patients with Cervical Spondylosis.

PubMed

Kalb, Samuel; Zaidi, Hasan A; Ribas-Nijkerk, Juan C; Sindhwani, Maughan K; Clark, Justin C; Martirosyan, Nikolay L; Theodore, Nicholas

2015-08-01

Hypertension and cervical spondylosis are diseases of the adult population that are approaching near pandemic proportions. However, the interactions between these two disease processes are poorly understood. We set out to determine the associations among systemic hypertension, clinical status, and imaging findings of spinal cord damage for patients with cervical stenosis. A retrospective chart review was performed on patients with symptomatic cervical stenosis related to degenerative disease and divided on the basis of outpatient blood pressure control (normal <140/<90 mm Hg). Sagittal T2-weighted magnetic resonance imaging (MRI) of the cervical spine was analyzed to determine the degree of maximal canal stenosis (MCS; %), surface area of increased signal intensity (ISI; cm(2)), and signal intensity ratio (SIR). Functional status was evaluated using the modified Japanese Orthopaedic Association (mJOA) scale and the Nurick scale. One hundred twenty-two patients were identified (64 hypertensive, 58 nonhypertensive). Likelihood of ISI was higher in hypertensive patients (P < 0.05). Average ISI was significantly higher in patients with uncontrolled blood pressure (P = 0.02) despite MCS being identical between the two groups. The mJOA and Nurick scores were worse for patients with systemic hypertension (P < 0.02). Diabetes mellitus and smoking history did not affect these findings. Persistent hypertension in outpatients is associated with worsened clinical status and increased markers of spinal cord damage on MRI. Perioperative management of blood pressure may serve to improve clinical outcomes. Larger prospective trials are necessary to further validate these findings. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

Romi, Fredrik; Naess, Halvor

2016-01-01

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

Recovery of locomotion in the cat following spinal cord lesions.

PubMed

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

2002-10-01

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

Spinal inhibition and motor function in adults with spastic cerebral palsy

PubMed Central

Condliffe, E. G.; Jeffery, D. T.; Emery, D. J.

2016-01-01

Key points Abnormal activation of motoneurons in the spinal cord by sensory pathways is thought to contribute to impaired movement control and spasticity in individuals with cerebral palsy.Here we use single motor unit recordings to show how individual motoneurons in the spinal cord respond to sensory inputs in a group of participants with cerebral palsy having different degrees of motor dysfunction.In participants who had problems walking independently and required assistive devices such as wheelchairs, sensory pathways only excited motoneurons in the spinal cord.In contrast, in participants with cerebral palsy who walked independently for long distances, sensory inputs both inhibited and excited motoneurons in the spinal cord, similar to what we found in uninjured control participants.These findings demonstrate that in individuals with severe cerebral palsy, inhibitory control of motoneurons from sensory pathways is reduced and may contribute to motor dysfunction and spasticity. Abstract Reduced inhibition of spinal motoneurons by sensory pathways may contribute to heightened reflex activity, spasticity and impaired motor function in individuals with cerebral palsy (CP). To measure if the activation of inhibitory post‐synaptic potentials (IPSPs) by sensory inputs is reduced in CP, the tonic discharge rate of single motor units from the soleus muscle was plotted time‐locked to the occurrence of a sensory stimulation to produce peri‐stimulus frequencygrams (PSFs). Stimulation to the medial arch of the foot was used to activate cutaneomuscular afferents in 17 adults with bilateral spastic CP and 15 neurologically intact (NI) peers. Evidence of IPSP activation from the PSF profiles, namely a marked pause or reduction in motor unit firing rates at the onset of the cutaneomuscular reflex, was found in all NI participants but in only half of participants with CP. In the other half of the participants with CP, stimulation of cutaneomuscular afferents produced a PSF profile indicative of a pure excitatory post‐synaptic potential, with firing rates increasing above the mean pre‐stimulus rate for 300 ms or more. The amplitude of motoneuron inhibition during the period of IPSP activation, as measured from the surface EMG, was less in participants with poor motor function as evaluated with the Gross Motor Functional Classification System (r = 0.72, P < 0.001) and the Functional Mobility Scale (r = −0.82, P < 0.001). These findings demonstrate that in individuals with CP, reduced activation of motoneuron IPSPs by sensory inputs is associated with reduced motor function and may contribute to enhanced reflexes and spasticity in CP. PMID:26842905

Cognitive performance of people with traumatic spinal cord injury: a cross-sectional study comparing people with subacute and chronic injuries.

PubMed

Molina, B; Segura, A; Serrano, J P; Alonso, F J; Molina, L; Pérez-Borrego, Y A; Ugarte, M I; Oliviero, A

2018-02-22

Cross-sectional study. To assess the impact of spinal cord injury (SCI) on cognitive function in individuals with subacute and chronic SCI. National Hospital for SCI patients (Spain). The present investigation was designed to determine the nature, pattern, and extent of cognitive deficits in a group of participants with subacute (n = 32) and chronic (n = 34) SCI, using a comprehensive battery of reliable and validated neuropsychological assessments to study a broad range of cognitive functions. Twenty-seven able-bodied subjects matched to the groups with SCI for age and educational level formed the control group. The neuropsychological assessment showed alterations in the domain of attention, processing speed, memory and learning, executive functions, and in recognition in participants with SCI. The prevalence of cognitive dysfunction in the chronic stage was also confirmed at the individual level. The comparison of the neuropsychological assessment between the groups with subacute and chronic SCI showed a worsening of cognitive functions in those with chronic SCI compared to the group with subacute SCI. In participants with SCI, cognitive dysfunctions are present in the subacute stage and worsen over time. From a clinical point of view, we confirmed the presence of cognitive dysfunction that may interfere with the first stage of rehabilitation which is the most intense and important. Moreover, cognitive dysfunction may be important beyond the end of the first stage of rehabilitation as it can affect an individual's quality of life and possible integration to society.

Central nervous system (image)

MedlinePlus

... receive nerve impulses from the spinal cord and cranial nerves. The spinal cord contains the nerves that carry messages between the brain and the body. Spinal cord injury can occur when there is damage to the cells within the spinal cord or ...

[The metabolic profilings study of serum and spinal cord from acute spinal cord injury rats ¹H NMR spectroscopy].

PubMed

Hu, Hua-Hui; Huang, Xiao-Long; Quan, Ren-Fu; Yang, Zong-Bao; Xu, Jing-Jing

2017-02-25

To establish the rat model of acute spinal cord injury, followed by aprimary study on this model with ¹H NMR based on metabonomics and to explore the metabonomics and biomarkers of spinal cord injury rat. Twenty eight-week-old adult male SD rats of clean grade, with body weight of (200±10) g, were divided into sham operation group and model group in accordance with the law of random numbers, and every group had 10 rats. The rats of sham operation group were operated without damaging the spinal cord, and rats of model group were made an animal model of spinal cord incomplete injury according to the modified Allen's method. According to BBB score to observate the motor function of rats on the 1th, 5th, and 7th days after surgery. Postoperative spinal cord tissue was collected in order to pathologic observation at the 7th day, and the metabolic profilings of serum and spinal cord from spinal cord injury rats were studied by ¹H NMR spectroscopy. The hindlimb motion of rats did not obviously change in sham operation group, there was no significant difference at each time point;and rats of model group occurred flaccid paralysis of both lower extremities, there was a significant difference at each time; there was significant differences between two groups at each time. Pathological results showed the spinal cord structure was normal with uniform innervation in shame group, while in model group, the spinal cord structure was mussy, and the neurons were decreased, with inflammatory cells and necrotic tissue. Analysis of metabonomics showed that concentration of very low density fat protein (VLDL), low density fat protein (LDL), glutamine, citric acid, dimethylglycine (DMG) in the serum and glutathione, 3-OH-butyrate, N-Acetyl-L-aspartic acid (NAA), glycerophosphocholine (GPC), glutamic acid, and ascorbate in spinal cord had significant changes( P <0.05). There are significant differences in metabolic profile from serum and spinal cord sample between model group and sham operation group, it conduces to explain the changes of small molecular substances in serum and spinal cord tissue after spinal cord injury, this provides the research basis for targeted research on the role of metabolic markers in patients with acute spinal cord injury.

Image analysis of open-door laminoplasty for cervical spondylotic myelopathy: comparing the influence of cord morphology and spine alignment.

PubMed

Lin, Bon-Jour; Lin, Meng-Chi; Lin, Chin; Lee, Meei-Shyuan; Feng, Shao-Wei; Ju, Da-Tong; Ma, Hsin-I; Liu, Ming-Ying; Hueng, Dueng-Yuan

2015-10-01

Previous studies have identified the factors affecting the surgical outcome of cervical spondylotic myelopathy (CSM) following laminoplasty. Nonetheless, the effect of these factors remains controversial. It is unknown about the association between pre-operative cervical spinal cord morphology and post-operative imaging result following laminoplasty. The goal of this study is to analyze the impact of pre-operative cervical spinal cord morphology on post-operative imaging in patients with CSM. Twenty-six patients with CSM undergoing open-door laminoplasty were classified according to pre-operative cervical spine bony alignment and cervical spinal cord morphology, and the results were evaluated in terms of post-operative spinal cord posterior drift, and post-operative expansion of the antero-posterior dura diameter. By the result of study, pre-operative spinal cord morphology was an effective classification in predicting surgical outcome - patients with anterior convexity type, description of cervical spinal cord morphology, had more spinal cord posterior migration than those with neutral or posterior convexity type after open-door laminoplasty. Otherwise, the interesting finding was that cervical spine Cobb's angle had an impact on post-operative spinal cord posterior drift in patients with neutral or posterior convexity type spinal cord morphology - the degree of kyphosis was inversely proportional to the distance of post-operative spinal cord posterior drift, but not in the anterior convexity type. These findings supported that pre-operative cervical spinal cord morphology may be used as screening for patients undergoing laminoplasty. Patients having neutral or posterior convexity type spinal cord morphology accompanied with kyphotic deformity were not suitable candidates for laminoplasty. Copyright © 2015 Elsevier B.V. All rights reserved.

Spinal cord herniation following cervical meningioma excision: a rare clinical entity and review of literature.

PubMed

Aiyer, Siddharth N; Shetty, Ajoy Prasad; Kanna, Rishi; Maheswaran, Anupama; Rajasekaran, S

2016-05-01

Spinal cord herniation following surgery is an extremely uncommon clinical condition with very few reports in published literature. This condition usually occurs as a spontaneous idiopathic phenomenon often in the thoracic spine or following a scenario of post traumatic spinal cord/nerve root injury. Rarely has it been reported following spinal cord tumor surgery. To document a case of cervical spinal cord herniation as a late onset complication following spinal cord tumor surgery with an atypical presentation of monoparesis. Case report. We describe the clinical presentation, operative procedure, post operative outcome and review of literature of this rare clinical condition. A 57-year-old man presented with right upper limb monoparesis due to a spinal cord herniation 6 years after a cervical intradural meningioma excision. The patients underwent surgery to reduce the herniation and duroplasty with subsequent complete resolution of symptoms. Spinal cord herniation must be considered as differential diagnosis in scenarios of spinal cord tumor excision presenting with late onset neurological deficit. These cases may present as paraparesis, Brown-sequard syndrome and rarely as in our case as monoparesis.

Assessments of sensory plasticity after spinal cord injury across species.

PubMed

Haefeli, Jenny; Huie, J Russell; Morioka, Kazuhito; Ferguson, Adam R

2017-06-23

Spinal cord injury (SCI) is a multifaceted phenomenon associated with alterations in both motor function and sensory function. A majority of patients with SCI report sensory disturbances, including not only loss of sensation, but in many cases enhanced abnormal sensation, dysesthesia and pain. Development of therapeutics to treat these abnormal sensory changes require common measurement tools that can enable cross-species translation from animal models to human patients. We review the current literature on translational nociception/pain measurement in SCI and discuss areas for further development. Although a number of tools exist for measuring both segmental and affective sensory changes, we conclude that there is a pressing need for better, integrative measurement of nociception/pain outcomes across species to enhance precise therapeutic innovation for sensory dysfunction in SCI. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluation of purinergic mechanism for the treatment of voiding dysfunction: a study in conscious spinal cord-injured rats.

PubMed

Lu, Shing-Hwa; Groat, William C de; Lin, Alex T L; Chen, Kuang-Kuo; Chang, Luke S

2007-10-01

To investigate the effect of a selective P2X(3-)P2X(2/3) purinergic receptor antagonist (a-317491) on detrusor hyperreflexia in conscious chronic spinal cord-injured female rats. Six chronic spinal cord-transected female Sprague-Dawley rats (290-336 g) were used in this study. Spinal transection at the T8-T9 segmental level was performed using aseptic techniques under halothane anesthesia. Fourteen to 16 weeks after spinal transection, A-317491, a selective P2X(3-)P2X(2/3) purinergic receptor antagonist, was administered intravenously in cystometry studies at increasing doses of 0.03, 0.1, 0.3, 1, 3, 10 and 30 micromol/kg at 40-50 minute intervals. Cystometrograms (CMGs) were performed before and after the administration of each dose of the drug. The continuous filling of CMGs revealed a large number of small-amplitude (> 8 cmH(2)O), non-voiding contractions (NVCs) (average, 9.7 per voiding cycle) preceding voiding contractions (mean amplitude, 31 cmH(2)O; duration, 2.5 minutes), which occurred at an interval of 539 seconds and at a pressure threshold of 5.7 cmH(2)O. When tested in a range of doses (0.03-30 micromol/kg, intravenous), A-317491 in doses between 1 and 30 micromol/kg significantly (p < 0.05) increased the interval between voids by 25%, reduced the number of NVCs by 42-62%, and increased the pressure threshold for voiding by 53-73%, but did not change the amplitude of the duration of the voiding contractions. The effects of the drug were apparent within 10 minutes following administration. These results indicate that purinergic mechanisms, presumably involving P2X(3) or P2X(2/3) receptors on bladder C-fiber afferent nerves, play an important role in the detrusor hyperreflexia that occurs after spinal cord injury in rats.

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

PubMed

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

2018-05-28

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

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

PubMed Central

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

2016-01-01

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

Brain protection by methylprednisolone in rats with spinal cord injury.

PubMed

Chang, Chia-Mao; Lee, Ming-Hsueh; Wang, Ting-Chung; Weng, Hsu-Huei; Chung, Chiu-Yen; Yang, Jen-Tsung

2009-07-01

Traumatic spinal cord injury is clinically treated by high doses of methylprednisolone. However, the effect of methylprednisolone on the brain in spinal cord injury patients has been little investigated. This experimental study examined Bcl-2 and Bax protein expression and Nissl staining to evaluate an apoptosis-related intracellular signaling event and final neuron death, respectively. Spinal cord injury produced a significant apoptotic change and cell death not only in the spinal cord but also in the supraventricular cortex and hippocampal cornu ammonis 1 region in the rat brains. The treatment of methylprednisolone increased the Bcl-2/Bax ratio and prevented neuron death for 1-7 days after spinal cord injury. These findings suggest that rats with spinal cord injury show ascending brain injury that could be restricted through methylprednisolone management.

[APPLICATION OF THREE DIMENSIONAL PRINTING ON MANUFACTURING BIONIC SCAFFOLDS OF SPINAL CORD IN RATS].

PubMed

Chen, Yisheng; Wang, Jingjing; Chen, Xuyi; Chen, Chong; Tu, Yue; Zhang, Sai; Li, Xiaohong

2015-03-01

To fabricate the bionic scaffolds of rat spinal cord by combining three dimensional (3D) printer and 3D software, so as to lay the foundation of theory and technology for the manufacture of scaffolds by using biomaterials. Three female Sprague Dawley rats were scanned by 7.0T MRI to obtain the shape and position data of the cross section and gray matter of T8 to T10 spinal cord. Combined with data of position and shape of nerve conduction beam, the relevant data were obtained via Getdata software. Then the 3D graphics were made and converted to stereolithography (STL) format by using SolidWorks software. Photosensitive resin was used as the materials of spinal cord scaffolds. The bionic scaffolds were fabricated by 3D printer. MRI showed that the section shape of T8 to T10 segments of the spinal cord were approximately oval with a relatively long sagittal diameter of (2.20 ± 0.52) mm and short transverse diameter of (2.05 ± 0.24) mm, and the data of nerve conduction bundle were featured in the STL format. The spinal cord bionic scaffolds of the target segments made by 3D printer were similar to the spinal cord of rat in the morphology and size, and the position of pores simulated normal nerve conduction of rat spinal cord. Spinal cord scaffolds produced by 3D printer which have similar shape and size of normal rat spinal cord are more bionic, and the procedure is simple. This technology combined with biomaterials is also promising in spinal cord repairing after spinal cord injury.

Spinal cord injury arising in anaesthesia practice.

PubMed

Hewson, D W; Bedforth, N M; Hardman, J G

2018-01-01

Spinal cord injury arising during anaesthetic practice is a rare event, but one that carries a significant burden in terms of morbidity and mortality. In this article, we will review the pathophysiology of spinal cord injury. We will then discuss injuries relating to patient position, spinal cord hypoperfusion and neuraxial techniques. The most serious causes of spinal cord injury - vertebral canal haematoma, spinal epidural abscess, meningitis and adhesive arachnoiditis - will be discussed in turn. For each condition, we draw attention to practical, evidence-based measures clinicians can undertake to reduce their incidence, or mitigate their severity. Finally, we will discuss transient neurological symptoms. Some cases of spinal cord injury during anaesthesia can be ascribed to anaesthesia itself, arising as a direct consequence of its conduct. The injury to a spinal nerve root by inaccurate and/or incautious needling during spinal anaesthesia is an obvious example. But in many cases, spinal cord injury during anaesthesia is not caused by, related to, or even associated with, the conduct of the anaesthetic. Surgical factors, whether direct (e.g. spinal nerve root damage due to incorrect pedicle screw placement) or indirect (e.g. cord ischaemia following aortic surgery) are responsible for a significant proportion of spinal cord injuries that occur concurrently with the delivery of regional or general anaesthesia. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

Chemokines in neuron-glial cell interaction and pathogenesis of neuropathic pain.

PubMed

Zhang, Zhi-Jun; Jiang, Bao-Chun; Gao, Yong-Jing

2017-09-01

Neuropathic pain resulting from damage or dysfunction of the nervous system is a highly debilitating chronic pain state and is often resistant to currently available treatments. It has become clear that neuroinflammation, mainly mediated by proinflammatory cytokines and chemokines, plays an important role in the establishment and maintenance of neuropathic pain. Chemokines were originally identified as regulators of peripheral immune cell trafficking and were also expressed in neurons and glial cells in the central nervous system. In recent years, accumulating studies have revealed the expression, distribution and function of chemokines in the spinal cord under chronic pain conditions. In this review, we provide evidence showing that several chemokines are upregulated after peripheral nerve injury and contribute to the pathogenesis of neuropathic pain via different forms of neuron-glia interaction in the spinal cord. First, chemokine CX3CL1 is expressed in primary afferents and spinal neurons and induces microglial activation via its microglial receptor CX3CR1 (neuron-to-microglia signaling). Second, CCL2 and CXCL1 are expressed in spinal astrocytes and act on CCR2 and CXCR2 in spinal neurons to increase excitatory synaptic transmission (astrocyte-to-neuron signaling). Third, we recently identified that CXCL13 is highly upregulated in spinal neurons after spinal nerve ligation and induces spinal astrocyte activation via receptor CXCR5 (neuron-to-astrocyte signaling). Strategies that target chemokine-mediated neuron-glia interactions may lead to novel therapies for the treatment of neuropathic pain.

In-vivo spinal cord deformation in flexion

NASA Astrophysics Data System (ADS)

Yuan, Qing; Dougherty, Lawrence; Margulies, Susan S.

1997-05-01

Traumatic mechanical loading of the head-neck complex results cervical spinal cord injury when the distortion of the cord is sufficient to produce functional or structural failure of the cord's neural and/or vascular components. Characterizing cervical spinal cord deformation during physiological loading conditions is an important step to defining a comprehensive injury threshold associated with acute spinal cord injury. In this study, in vivo quasi- static deformation of the cervical spinal cord during flexion of the neck in human volunteers was measured using magnetic resonance (MR) imaging of motion with spatial modulation of magnetization (SPAMM). A custom-designed device was built to guide the motion of the neck and enhance more reproducibility. the SPAMM pulse sequence labeled the tissue with a series of parallel tagging lines. A single- shot gradient-recalled-echo sequence was used to acquire the mid-sagittal image of the cervical spine. A comparison of the tagged line pattern in each MR reference and deformed image pair revealed the distortion of the spinal cord. The results showed the cervical spinal cord elongates during head flexion. The elongation experienced by the spinal cord varies linearly with head flexion, with the posterior surface of the cord stretching more than the anterior surface. The maximal elongation of the cord is about 12 percent of its original length.

Rhabdomyolysis and acute kidney injury in patients with traumatic spinal cord injury

PubMed Central

Galeiras, Rita; Mourelo, Mónica; Pértega, Sonia; Lista, Amanda; Ferreiro, Mª Elena; Salvador, Sebastián; Montoto, Antonio; Rodríguez, Antonio

2016-01-01

Background: Patients with acute traumatic spinal cord injuries (SCIs) exhibit factors that, in other populations, have been associated with rhabdomyolysis. Purpose: The aim of the study is to determine the incidence of rhabdomyolysis in patients with acute traumatic SCI admitted to the Intensive Care Unit (ICU), as well as the development of secondary acute kidney injury and associated factors. Study Design and Setting: This was an observational, retrospective study. Patient Sample: All adult patients admitted to the ICU with acute traumatic SCI who presented rhabdomyolysis, diagnosed through creatine phosphokinase (CPK) levels >500 IU/L. Outcome Measures: Incidence of rhabdomyolysis and subsequent renal dysfunction was calculated. Materials and Methods: Data about demographic variables, comorbidity, rhabdomyolysis risk factors, and variables involving SCI, severity scores, and laboratory parameters were obtained from clinical records. Multivariate logistic regression was used to identify renal injury risk factors. Results: In 2006–2014, 200 patients with acute SCI were admitted to ICU. Of these, 103 had rhabdomyolysis (incidence = 51.5%; 95% confidence interval [CI]: 44.3%–58.7%). The most typical American Spinal Injury Association classification was A (70.3%). The injury severity score was 30.3 ± 12.1 and sequential organ failure assessment (SOFA) score was 5.6 ± 3.3 points. During their stay, 57 patients (55.3%; 95% CI: 45.2%–65.4%) presented renal dysfunction (creatinine ≥1.2 mg/dL). In the multivariate analysis, variables associated with renal dysfunction were creatinine at admission (odds ratio [OR] = 9.20; P = 0.006) and hemodynamic SOFA score the day following admission (OR = 1.33; P = 0.024). Creatinine was a better predictor of renal dysfunction than the peak CPK value during the rhabdomyolysis (area under the receiver operating characteristic curve: 0.91 vs. 0.63, respectively). Conclusions: Rhabdomyolysis is a frequent condition in patients with acute traumatic SCI admitted to the ICU, and renal dysfunction occurs in half of the cases. Creatinine values should be requested starting at the admission while neither the peak CPK values nor the hemodynamic SOFA scores could be used to properly discriminate between patients with and without renal dysfunction. PMID:27688625

Experimental spinal cord trauma: a review of mechanically induced spinal cord injury in rat models.

PubMed

Abdullahi, Dauda; Annuar, Azlina Ahmad; Mohamad, Masro; Aziz, Izzuddin; Sanusi, Junedah

2017-01-01

It has been shown that animal spinal cord compression (using methods such as clips, balloons, spinal cord strapping, or calibrated forceps) mimics the persistent spinal canal occlusion that is common in human spinal cord injury (SCI). These methods can be used to investigate the effects of compression or to know the optimal timing of decompression (as duration of compression can affect the outcome of pathology) in acute SCI. Compression models involve prolonged cord compression and are distinct from contusion models, which apply only transient force to inflict an acute injury to the spinal cord. While the use of forceps to compress the spinal cord is a common choice due to it being inexpensive, it has not been critically assessed against the other methods to determine whether it is the best method to use. To date, there is no available review specifically focused on the current compression methods of inducing SCI in rats; thus, we performed a systematic and comprehensive publication search to identify studies on experimental spinalization in rat models, and this review discusses the advantages and limitations of each method.

Electroencephalographic evoked pain response is suppressed by spinal cord stimulation in complex regional pain syndrome: a case report.

PubMed

Hylands-White, Nicholas; Duarte, Rui V; Beeson, Paul; Mayhew, Stephen D; Raphael, Jon H

2016-12-01

Pain is a subjective response that limits assessment. The purpose of this case report was to explore how the objectivity of the electroencephalographic response to thermal stimuli would be affected by concurrent spinal cord stimulation. A patient had been implanted with a spinal cord stimulator for the management of complex regional pain syndrome of both hands for 8 years. Following ethical approval and written informed consent we induced thermal stimuli using the Medoc PATHWAY Pain & Sensory Evaluation System on the right hand of the patient with the spinal cord stimulator switched off and with the spinal cord stimulator switched on. The patient reported a clinically significant reduction in thermal induced pain using the numerical rating scale (71.4 % reduction) with spinal cord stimulator switched on. Analysis of electroencephalogram recordings indicated the occurrence of contact heat evoked potentials (N2-P2) with spinal cord stimulator off, but not with spinal cord stimulator on. This case report suggests that thermal pain can be reduced in complex regional pain syndrome patients with the use of spinal cord stimulation and offers objective validation of the reported outcomes with this treatment.

Rehabilitation of people with spinal cord damage due to tumor: literature review, international survey and practical recommendations for optimizing their rehabilitation.

PubMed

New, Peter Wayne; Marshall, Ruth; Stubblefield, Michael D; Scivoletto, Giorgio

2017-03-01

People with spinal cord dysfunction (SCDys) due to tumor (benign and malignant) pose enormous rehabilitation challenges. Objectives were: conduct literature search regarding epidemiology, clinical features and outcomes for SCDys due to tumor following rehabilitation, the ideal setting for rehabilitation and practical considerations for rehabilitation; and propose framework and practical considerations for managing people with SCDys due to tumor in spinal rehabilitation units (SRUs). Survey of rehabilitation health care professionals, consensus opinion from experts and literature search. Workshop at International Spinal Cord Society and American Spinal Injury Association combined annual meeting, May 16, 2015, Montréal, Canada. Workshop attendees and experts in the rehabilitation of people with SCDys due to tumor. Reports of services offered to people with SCDys due to tumor, including whether those with benign and malignant tumors are admitted into rehabilitation, any admission criteria used and the rational for declining admission. Most respondents (n = 33, 83%) reported that people with benign tumors were routinely admitted for rehabilitation but only 18 (45%) reported that people with malignant tumors were routinely admitted. A range of criteria and reasons for declining admission were given. Evidence from the literature and the opinion of experts support the admission of people with SCDys due to tumor into specialist SRUs. A framework and practical considerations for managing people with SCDys due to tumor in SRUs are proposed. Patients with tumor causing SCDys should be given greater access to specialist SRU in order to achieve the best outcomes.

Rehabilitation of people with spinal cord damage due to tumor: literature review, international survey and practical recommendations for optimizing their rehabilitation

PubMed Central

Marshall, Ruth; Stubblefield, Michael D.; Scivoletto, Giorgio

2017-01-01

Background People with spinal cord dysfunction (SCDys) due to tumor (benign and malignant) pose enormous rehabilitation challenges. Objectives were: conduct literature search regarding epidemiology, clinical features and outcomes for SCDys due to tumor following rehabilitation, the ideal setting for rehabilitation and practical considerations for rehabilitation; and propose framework and practical considerations for managing people with SCDys due to tumor in spinal rehabilitation units (SRUs). Design Survey of rehabilitation health care professionals, consensus opinion from experts and literature search. Setting Workshop at International Spinal Cord Society and American Spinal Injury Association combined annual meeting, May 16, 2015, Montréal, Canada. Participants Workshop attendees and experts in the rehabilitation of people with SCDys due to tumor. Outcomes Measures Reports of services offered to people with SCDys due to tumor, including whether those with benign and malignant tumors are admitted into rehabilitation, any admission criteria used and the rational for declining admission. Results Most respondents (n = 33, 83%) reported that people with benign tumors were routinely admitted for rehabilitation but only 18 (45%) reported that people with malignant tumors were routinely admitted. A range of criteria and reasons for declining admission were given. Evidence from the literature and the opinion of experts support the admission of people with SCDys due to tumor into specialist SRUs. Conclusions A framework and practical considerations for managing people with SCDys due to tumor in SRUs are proposed. Patients with tumor causing SCDys should be given greater access to specialist SRU in order to achieve the best outcomes. PMID:27088581

Noninvasive Optical Monitoring of Spinal Cord Hemodynamics and Oxygenation after Acute Spinal Cord Injury

DTIC Science & Technology

2017-09-01

oxygen delivery and oxygen consumption . The oxygen portion of the Oxylite probe emits short pulses of blue LED light resulting in a fluorescent...Award Number: W81XWH-16-1-0602 TITLE: Noninvasive Optical Monitoring of Spinal Cord Hemodynamics and Oxygenation after Acute Spinal Cord Injury...COVERED 1 Sep 2016 - 31 Aug 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Noninvasive Optical Monitoring of Spinal Cord Hemodynamics and Oxygenation

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

PubMed

Fakhoury, Marc

2015-01-01

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

Meningocele repair - series (image)

MedlinePlus

... containing a portion of the spinal cord membrane (meninges), spinal fluid, and a portion of spinal cord ... The spinal cord is covered with the membranes (meninges) and the skin is closed over the protruding ...

Part 1: recognizing neonatal spinal cord injury.

PubMed

Brand, M Colleen

2006-02-01

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.

Challenges in clinical applications of brain computer interfaces in individuals with spinal cord injury

PubMed Central

Rupp, Rüdiger

2014-01-01

Brain computer interfaces (BCIs) are devices that measure brain activities and translate them into control signals used for a variety of applications. Among them are systems for communication, environmental control, neuroprostheses, exoskeletons, or restorative therapies. Over the last years the technology of BCIs has reached a level of matureness allowing them to be used not only in research experiments supervised by scientists, but also in clinical routine with patients with neurological impairments supervised by clinical personnel or caregivers. However, clinicians and patients face many challenges in the application of BCIs. This particularly applies to high spinal cord injured patients, in whom artificial ventilation, autonomic dysfunctions, neuropathic pain, or the inability to achieve a sufficient level of control during a short-term training may limit the successful use of a BCI. Additionally, spasmolytic medication and the acute stress reaction with associated episodes of depression may have a negative influence on the modulation of brain waves and therefore the ability to concentrate over an extended period of time. Although BCIs seem to be a promising assistive technology for individuals with high spinal cord injury systematic investigations are highly needed to obtain realistic estimates of the percentage of users that for any reason may not be able to operate a BCI in a clinical setting. PMID:25309420

Prophylactic neuroprotective efficiency of co-administration of Ginkgo biloba and Trifolium pretense against sodium arsenite-induced neurotoxicity and dementia in different regions of brain and spinal cord of rats.

PubMed

Abdou, Heba M; Yousef, Mokhtar I; El Mekkawy, Desouki A; Al-Shami, Ahmed S

2016-08-01

The present study was carried out to evaluate the potential protective role of co-administration of Ginkgo biloba, Trifolium pretenseagainst sodium arsenite-induced neurotoxicity in different parts of brain (Cerebral cortex, Hippocampus, striatum and Hind brain) and in the spinal cord of rats. Sodium arsenite caused impairment in the acquisition and learning in all the behavioral tasks and caused significant increase in tumor necrosis factor-α,thiobarbituric acid-reactive substances andlipid profile, while caused significant decrease in glutathione, total thiol content, total antioxidant capacity, acetylcholinesterase, monoamine oxidase and ATPases activities. These results were confirmed by histopathological, fluorescence and scanning electron microscopy examination of different regions of brain. From these results sodium arsenite-induced neurodegenerative disorder in different regions of brain and spinal cord and this could be mediated through modifying the intracellular brain ions homeostasis, cholinergic dysfunction and oxidative damage. The presence of Ginkgo biloba and/orTrifolium pretense with sodium arsenite minimized its neurological damages. It was pronounced that using Ginkgo biloba and Trifolium pretense in combination was more effective as protective agents compared to use eachone of them alone. Copyright © 2016 Elsevier Ltd. All rights reserved.

Retraining the injured spinal cord

NASA Technical Reports Server (NTRS)

Edgerton, V. R.; Leon, R. D.; Harkema, S. J.; Hodgson, J. A.; London, N.; Reinkensmeyer, D. J.; Roy, R. R.; Talmadge, R. J.; Tillakaratne, N. J.; Timoszyk, W.;

A spinal thecal sac constriction model supports the theory that induced pressure gradients in the cord cause edema and cyst formation.

PubMed

Josephson, A; Greitz, D; Klason, T; Olson, L; Spenger, C

2001-03-01

Spinal cord cysts are a devastating condition that occur secondary to obstructions of the spinal canal, which may be caused by congenital malformations, trauma, spinal canal stenosis, tumors, meningitis, or arachnoiditis. A hypothesis that could explain how spinal cord cysts form in these situations has been presented recently. Therefore, a novel spinal thecal sac constriction model was implemented to test various aspects of this hypothesis. Thecal sac constriction was achieved by subjecting rats to an extradural silk ligature at the T8 spinal cord level. Rats with complete spinal cord transection served as a second model for comparison. The animals underwent high-resolution magnetic resonance imaging and histological analysis. Thecal sac constriction caused edema cranial and caudal to the ligation within 3 weeks, and cysts developed after 8 to 13 weeks. In contrast, cysts in rats with spinal cord transection were located predominantly in the cranial spinal cord. Histological sections of spinal cords confirmed the magnetic resonance imaging results. Magnetic resonance imaging provided the specific advantage of enabling characterization of events as they occurred repeatedly over time in the spinal cords of individual living animals. The spinal thecal sac constriction model proved useful for investigation of features of the cerebrospinal fluid pulse pressure theory. Edema and cyst distributions were in accordance with this theory. We conclude that induced intramedullary pressure gradients originating from the cerebrospinal fluid pulse pressure may underlie cyst formation in the vicinity of spinal canal obstructions and that cysts are preceded by edema.

Clinical evaluation of an innovative operative procedure in the treatment of the tethered cord syndrome.

PubMed

Hou, Yang; Sun, Jingchuan; Shi, Jiangang; Guo, Yongfei; Wang, Yuan; Shi, Guodong; Xu, Guohua

2018-06-01

The tethered cord syndrome (TCS) characterized by urination dysfunction has long been a worldwide clinical problem, of which clinical effects remains controversial. The objective of this study was to evaluate the clinical effects of an innovative surgical method for the treatment of TCS. This is a retrospective clinical study. There were 15 patients included in this study. The visual analog scale (VAS) and the Japanese Orthopaedic Association (JOA) scores were evaluated. The incidence of complications after surgery was also analyzed. A total of 15 patients including 9 men and 6 women with TCS underwent homogeneous spinal-shortening axial decompression (HSAD) from September 2011 to February 2015. The average age at the time of surgery was 38.1±17.7 years. The average postoperative follow-up period was 21.5±7.5 months. The VAS and JOA scores were used to evaluate the clinical effects of the new operational procedure. In addition, the incidence of complications was also recorded and analyzed. The VAS scores decreased from 3.93±2.52 to 1.80±1.21 at the final follow-up after surgery with a significant statistical difference (p=.006). The JOA scores also significantly increased from 9.93±3.43 to 21.20±4.18 at the final follow-up (p<.001). Fourteen cases (93.3%) with bladder dysfunction and 7 cases with sensory dysfunction of the lower limbs (87.5%) had a significant improvement postoperatively. Complications such as infection, pulmonary embolism, nerve injury, and broken rod were not observed during the follow-up period. The operation of HSAD was an effective and safe surgical method for TCS, which can achieve direct decompression of the tethered spinal cord. Copyright © 2017. Published by Elsevier Inc.

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

PubMed Central

Wieraszko, Andrzej

2008-01-01

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

Clinical presentation, imaging findings, and prognosis of spinal dural arteriovenous fistula.

PubMed

Lee, Jookyung; Lim, Young-Min; Suh, Dae Chul; Rhim, Seung Chul; Kim, Sang Joon; Kim, Kwang-Kuk

2016-04-01

Spinal dural arteriovenous fistula (SDAVF) is a relatively common acquired vascular malformation of the spinal cord. Assessment of a SDAVF is often difficult because of non-specific findings on non-invasive imaging modalities. Diagnosis of a SDAVF is often delayed, and some patients receive unnecessary treatment and treatment delays, often resulting in a poor outcome. The aim of this study was to characterize the clinical presentation, typical imaging findings, and long-term outcome of SDAVF. Forty patients (13 women, 27 men; mean age 58.18 ± standard deviation 14.75 years) who were treated at our hospital from June 1992 to March 2014 were retrospectively reviewed. We investigated the baseline characteristics, clinical presentation, imaging findings, treatment modalities, and outcome of the patients. The most common clinical presentation was a sensory symptom (80%), followed by motor weakness (70%), and sphincter dysfunction (62.5%). Roughly one-third (32.5%) of patients had a stepwise progression of fluctuating weakness and sensory symptoms, but the most common presentation was chronic progressive myelopathic symptoms (47.5%). Thirty-four patients (85%) had T2 signal change on the spinal cord MRI, indicative of cord edema. Thirty-eight patients had typical perimedullary vessel flow voids on T2-weighted MRI. Twenty-eight patients were treated with endovascular embolization, five patients underwent surgery, and four patients underwent both. Clinical outcome was determined by severity of initial deficit (p=0.008), extent of cord edema (p=0.010), treatment failure (p=0.004), and a residual fistula (p=0.017). SDAVF causes a treatable myelopathy, so early diagnosis and intervention is essential. Copyright © 2015 Elsevier Ltd. All rights reserved.

Top ten research priorities for spinal cord injury: the methodology and results of a British priority setting partnership.

PubMed

van Middendorp, J J; Allison, H C; Ahuja, S; Bracher, D; Dyson, C; Fairbank, J; Gall, A; Glover, A; Gray, L; Masri, W El; Uttridge, A; Cowan, K

2016-05-01

This is a mixed-method consensus development project. The objective of this study was to identify a top ten list of priorities for future research into spinal cord injury (SCI). The British Spinal Cord Injury Priority Setting Partnership was established in 2013 and completed in 2014. Stakeholders included consumer organisations, healthcare professional societies and caregivers. This partnership involved the following four key stages: (i) gathering of research questions, (ii) checking of existing research evidence, (iii) interim prioritisation and (iv) a final consensus meeting to reach agreement on the top ten research priorities. Adult individuals with spinal cord dysfunction because of trauma or non-traumatic causes, including transverse myelitis, and individuals with a cauda equina syndrome (henceforth grouped and referred to as SCI) were invited to participate in this priority setting partnership. We collected 784 questions from 403 survey respondents (290 individuals with SCI), which, after merging duplicate questions and checking systematic reviews for evidence, were reduced to 109 unique unanswered research questions. A total of 293 people (211 individuals with SCI) participated in the interim prioritisation process, leading to the identification of 25 priorities. At a final consensus meeting, a representative group of individuals with SCI, caregivers and health professionals agreed on their top ten research priorities. Following a comprehensive, rigorous and inclusive process, with participation from individuals with SCI, caregivers and health professionals, the SCI research agenda has been defined by people to whom it matters most and should inform the scope and future activities of funders and researchers for the years to come. The NIHR Oxford Biomedical Research Centre provided core funding for this project.

Exploration of Spinal Cord Aging-Related Proteins Using a Proteomics Approach.

PubMed

Kamiya, Koshiro; Furuya, Takeo; Hashimoto, Masayuki; Mannoji, Chikato; Inada, Taigo; Ota, Mitsutoshi; Maki, Satoshi; Ijima, Yasushi; Saito, Junya; Kitamura, Mitsuhiro; Ohtori, Seiji; Orita, Sumihisa; Inage, Kazuhide; Yamazaki, Masashi; Koda, Masao

2017-01-01

How aging affects the spinal cord at a molecular level is unclear. The aim of this study was to explore spinal cord aging-related proteins that may be involved in pathological mechanisms of age-related changes in the spinal cord. Spinal cords of 2-year-old and 8-week-old female Sprague-Dawley rats were dissected from the animals. Protein samples were subjected to 2-dimentional polyacrylamide gel electrophoresis followed by mass spectrometry. Screened proteins were further investigated with immunohistochemistry and Western blotting. Among the screened proteins, we selected α-crystallin B-subunit (αB-crystallin) and peripherin for further investigation because these proteins were previously reported to be related to central nervous system pathologies. Immunohistochemistry and Western blotting revealed significant upregulation of αB-crystallin and peripherin expression in aged rat spinal cord. Further exploration is needed to elucidate the precise mechanism and potential role of these upregulated proteins in spinal cord aging processes.

Spinal Cord Lesions in Congenital Toxoplasmosis Demonstrated with Neuroimaging, Including Their Successful Treatment in an Adult.

PubMed

Burrowes, Delilah; Boyer, Kenneth; Swisher, Charles N; Noble, A Gwendolyn; Sautter, Mari; Heydemann, Peter; Rabiah, Peter; Lee, Daniel; McLeod, Rima

2012-03-01

Neuroimaging studies for persons in the National Collaborative Chicago-Based Congenital Toxoplasmosis Study (NCCCTS) with symptoms and signs referable to the spinal cord were reviewed. Three infants had symptomatic spinal cord lesions, another infant a Chiari malformation, and another infant a symptomatic peri-spinal cord lipoma. One patient had an unusual history of prolonged spinal cord symptoms presenting in middle age. Neuroimaging was used to establish her diagnosis and response to treatment. This 43 year-old woman with congenital toxoplasmosis developed progressive leg spasticity, weakness, numbness, difficulty walking, and decreased visual acuity and color vision without documented re-activation of her chorioretinal disease. At 52 years of age, spinal cord lesions in locations correlating with her symptoms and optic atrophy were diagnosed with 3 Tesla MRI scan. Treatment with pyrimethamine and sulfadiazine decreased her neurologic symptoms, improved her neurologic examination, and resolved her enhancing spinal cord lesions seen on MRI.

Are there endogenous stem cells in the spinal cord?

PubMed

Ferrucci, Michela; Ryskalin, Larisa; Busceti, Carla L; Gaglione, Anderson; Biagioni, Francesca; Fornai, Francesco

2017-12-01

Neural progenitor cells (NPC) represent the stem-like niche of the central nervous system that maintains a regenerative potential also in the adult life. Despite NPC in the brain are well documented, the presence of NPC in the spinal cord has been controversial for a long time. This is due to a scarce activity of NPC within spinal cord, which also makes difficult their identification. The present review recapitulates the main experimental studies, which provided evidence for the occurrence of NPC within spinal cord, with a special emphasis on spinal cord injury and amyotrophic lateral sclerosis. By using experimental models, here we analyse the site-specificity, the phenotype and the main triggers of spinal cord NPC. Moreover, data are reported on the effect of specific neurogenic stimuli on these spinal cord NPC in an effort to comprehend the endogenous neurogenic potential of this stem cell niche.

Sudden death in Leigh syndrome: an autopsy case.

PubMed

Ventura, Francesco; Rocca, Gabriele; Gentile, Raffaella; De Stefano, Francesco

2012-09-01

The present report describes the sudden death of a 3-year-old female child who had been clinically diagnosed with Leigh syndrome.Leigh syndrome is a heterogeneous progressive neurodegenerative disorder, which is characterized by focal or bilateral lesions in the thalamus, basal ganglia, brainstem, cerebellum, and spinal cord. Affected patients exhibit a variable clinical picture that frequently includes psychomotor retardation or regression, recurrent episodes of vomiting, failure to thrive, and signs of brainstem and basal ganglia dysfunction.The child was found dead in bed. Autopsy described the presence of symmetrical, necrotizing lesions scattered within the basal ganglia, thalamus, diencephalon, brainstem, and spinal-cord gray matter and revealed the presence of gastric contents in the upper and lower airways. We report the results of genetic investigations and describe the histological and immunohistochemical features that confirmed the diagnosis. These findings suggest that Leigh syndrome should be regarded as predisposing children to sudden death, especially by asphyxia secondary to the neurological disorder.

21 CFR 882.5880 - Implanted spinal cord stimulator for pain relief.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted spinal cord stimulator for pain relief. 882.5880 Section 882.5880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Implanted spinal cord stimulator for pain relief. (a) Identification. An implanted spinal cord stimulator...

76 FR 71623 - Agency Information Collection (Spinal Cord Injury Patient Care Survey) Under OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-18

... Collection (Spinal Cord Injury Patient Care Survey) Under OMB Review AGENCY: Veterans Benefits Administration... INFORMATION: Title: Spinal Cord Injury Patient Care Survey, VA Form 10-0515. OMB Control Number: OMB Control... 10-0515 will be used to determine spinal cord patients' satisfaction with VA rehabilitation and...

DTI and pathological changes in a rabbit model of radiation injury to the spinal cord after 125I radioactive seed implantation

PubMed Central

Cao, Xia; Fang, Le; Cui, Chuan-yu; Gao, Shi; Wang, Tian-wei

2018-01-01

Excessive radiation exposure may lead to edema of the spinal cord and deterioration of the nervous system. Magnetic resonance imaging can be used to judge and assess the extent of edema and to evaluate pathological changes and thus may be used for the evaluation of spinal cord injuries caused by radiation therapy. Radioactive 125I seeds to irradiate 90% of the spinal cord tissue at doses of 40–100 Gy (D90) were implanted in rabbits at T10 to induce radiation injury, and we evaluated their safety for use in the spinal cord. Diffusion tensor imaging showed that with increased D90, the apparent diffusion coefficient and fractional anisotropy values were increased. Moreover, pathological damage of neurons and microvessels in the gray matter and white matter was aggravated. At 2 months after implantation, obvious pathological injury was visible in the spinal cords of each group. Magnetic resonance diffusion tensor imaging revealed the radiation injury to the spinal cord, and we quantified the degree of spinal cord injury through apparent diffusion coefficient and fractional anisotropy. PMID:29623940

Effects of pacing-induced myocardial stress and spinal cord stimulation on whole body and cardiac norepinephrine spillover.

PubMed

Norrsell, H; Eliasson, T; Mannheimer, C; Augustinsson, L E; Bergh, C H; Andersson, B; Waagstein, F; Friberg, P

1997-12-01

Spinal cord stimulation has been used in the treatment of intractable angina pectoris since the beginning of the 1980s. This study was designed to investigate whether the documented anti-ischaemic effects of spinal cord stimulation are mediated through a decrease in sympathetic activity. Ten patients with a spinal cord stimulator implanted as anti-anginal treatment were included in the study. Atrial pacing until the patient experienced moderate angina was performed and after 50 min rest the procedure was repeated during spinal cord stimulation. Total body and cardiac norepinephrine spillover was calculated and the former was found to have increased during pacing (47%, P = 0.02). When spinal cord stimulation was applied, total body norepinephrine spillover decreased at a comparable pacing rate (18%, P = 0.02). Cardiac norepinephrine spillover was not affected during the procedure. The results of this study indicate that the anti-ischaemic effect of spinal cord stimulation is not due to reduced cardiac sympathetic activity. However, spinal cord stimulation decreases overall sympathetic activity which may benefit the heart, possibly by reducing oxygen demand.

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

PubMed Central

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

2015-01-01

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

Spinal cord regeneration in Xenopus tadpoles proceeds through activation of Sox2-positive cells

PubMed Central

2012-01-01

Background In contrast to mammals, amphibians, such as adult urodeles (for example, newts) and anuran larvae (for example, Xenopus) can regenerate their spinal cord after injury. However, the cellular and molecular mechanisms involved in this process are still poorly understood. Results Here, we report that tail amputation results in a global increase of Sox2 levels and proliferation of Sox2+ cells. Overexpression of a dominant negative form of Sox2 diminished proliferation of spinal cord resident cells affecting tail regeneration after amputation, suggesting that spinal cord regeneration is crucial for the whole process. After spinal cord transection, Sox2+ cells are found in the ablation gap forming aggregates. Furthermore, Sox2 levels correlated with regenerative capabilities during metamorphosis, observing a decrease in Sox2 levels at non-regenerative stages. Conclusions Sox2+ cells contribute to the regeneration of spinal cord after tail amputation and transection. Sox2 levels decreases during metamorphosis concomitantly with the lost of regenerative capabilities. Our results lead to a working hypothesis in which spinal cord damage activates proliferation and/or migration of Sox2+ cells, thus allowing regeneration of the spinal cord after tail amputation or reconstitution of the ependymal epithelium after spinal cord transection. PMID:22537391

Twiddler's syndrome in spinal cord stimulation.

PubMed

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

2016-01-01

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

Characteristics of spinal cord stroke in clinical neurology.

PubMed

Romi, Fredrik; Naess, Halvor

2011-01-01

Spinal cord stroke accounts for about 0.3% of all strokes in our department. Thirty-two patients (15 males, 17 females; mean age 63.3 years) treated in the period 1995-2010 were included. Patients underwent thorough investigation including the use of different stroke scales (National Institute of Health Stroke Scale, Barthel Index and modified Rankin Scale). Twenty-eight patients had infarctions, 3 had hemorrhages, and 1 had arterio-venous fistula. Twenty-eight spinal cord strokes were spontaneous, 2 were secondary to aorta aneurysms, and 2 post surgery. Biphasic ictus was seen in 17% of all spontaneous infarctions. Younger age, male gender, hypertension, diabetes mellitus, and higher blood glucose on admission regardless of diabetes mellitus, were risk factors associated with more severe spinal cord stroke. Treatment and prevention of these risk factors should be essential in spinal cord stroke. We recommend a clinical classification into upper (cervical) and lower (thoracic or medullary conus) spinal cord strokes. Patients with upper strokes in this study had more severe strokes initially, but they had a better prognosis. Therefore it is important to identify this patient group.Acute sensory spinal cord deficit symptoms, common initial symptoms in biphasic spinal cord strokes, should be considered as possible spinal cord stroke, especially when preceded by radiating pain between the shoulders. Copyright © 2011 S. Karger AG, Basel.

Fascia: A missing link in our understanding of the pathology of fibromyalgia.

PubMed

Liptan, Ginevra L

2010-01-01

Significant evidence exists for central sensitization in fibromyalgia, however the cause of this process in fibromyalgia-and how it relates to other known abnormalities in fibromyalgia-remains unclear. Central sensitization occurs when persistent nociceptive input leads to increased excitability in the dorsal horn neurons of the spinal cord. In this hyperexcited state, spinal cord neurons produce an enhanced responsiveness to noxious stimulation, and even to formerly innocuous stimulation. No definite evidence of muscle pathology in fibromyalgia has been found. However, there is some evidence for dysfunction of the intramuscular connective tissue, or fascia, in fibromyalgia. This paper proposes that inflammation of the fascia is the source of peripheral nociceptive input that leads to central sensitization in fibromyalgia. The fascial dysfunction is proposed to be due to inadequate growth hormone production and HPA axis dysfunction in fibromyalgia. Fascia is richly innervated, and the major cell of the fascia, the fibroblast, has been shown to secrete pro-inflammatory cytokines, particularly IL-6, in response to strain. Recent biopsy studies using immuno-histochemical staining techniques have found increased levels of collagen and inflammatory mediators in the connective tissue surrounding the muscle cells in fibromyalgia patients. The inflammation of the fascia is similar to that described in conditions such as plantar fasciitis and lateral epicondylitis, and may be better described as a dysfunctional healing response. This may explain why NSAIDs and oral steroids have not been found effective in fibromyalgia. Inflammation and dysfunction of the fascia may lead to central sensitization in fibromyalgia. If this hypothesis is confirmed, it could significantly expand treatment options to include manual therapies directed at the fascia such as Rolfing and myofascial release, and direct further research on the peripheral pathology in fibromyalgia to the fascia.

Electrical field distribution within the injured cat spinal cord: injury potentials and field distribution.

PubMed

Khan, T; Myklebust, J; Swiontek, T; Sayers, S; Dauzvardis, M

1994-12-01

This study investigated the spontaneous injury potentials measured after contusion or transection injury to the cat spinal cord. In addition, the distribution of electrical field potentials on the surface and within the spinal cord were measured following applied electrical fields after transection and contusion injuries. After transection of the spinal cord, the injury potentials were -19.8 +/- 2.6 mV; after contusion of the spinal cord, the injury potentials were -9.5 +/- 2.2 mV. These potentials returned to control values within 2.5-4h after injury. The electrical field distribution measured on the dorsal surface, as well as within the spinal cord, after the application of a 10 microA current, showed little difference between contusion and transection injuries. Scalar potential fields were measured using two configurations of stimulating electrodes: dorsal to dorsal (D-D), in which both electrodes were placed epidurally on the dorsal surface of the spinal cord, and ventral to dorsal (V-D), in which one electrode was placed dorsally and one ventrally. As reported in normal uninjured cats, the total current in the midsagittal plane for the D-D configuration was largely confined to the dorsal portion of the spinal cord; with the V-D configuration, the current distribution was uniform throughout the spinal cord. In the injured spinal cord, the equipotential lines midway between the stimulating electrodes have a wider separation than in the uninjured spinal cord. Because the magnitude of the electrical field E is equal to the current density J multiplied by the resistivity r, this suggests that either the current density is reduced or that the resistivity is reduced.

Topologically preserving straightening of spinal cord MRI.

PubMed

De Leener, Benjamin; Mangeat, Gabriel; Dupont, Sara; Martin, Allan R; Callot, Virginie; Stikov, Nikola; Fehlings, Michael G; Cohen-Adad, Julien

2017-10-01

To propose a robust and accurate method for straightening magnetic resonance (MR) images of the spinal cord, based on spinal cord segmentation, that preserves spinal cord topology and that works for any MRI contrast, in a context of spinal cord template-based analysis. The spinal cord curvature was computed using an iterative Non-Uniform Rational B-Spline (NURBS) approximation. Forward and inverse deformation fields for straightening were computed by solving analytically the straightening equations for each image voxel. Computational speed-up was accomplished by solving all voxel equation systems as one single system. Straightening accuracy (mean and maximum distance from straight line), computational time, and robustness to spinal cord length was evaluated using the proposed and the standard straightening method (label-based spline deformation) on 3T T 2 - and T 1 -weighted images from 57 healthy subjects and 33 patients with spinal cord compression due to degenerative cervical myelopathy (DCM). The proposed algorithm was more accurate, more robust, and faster than the standard method (mean distance = 0.80 vs. 0.83 mm, maximum distance = 1.49 vs. 1.78 mm, time = 71 vs. 174 sec for the healthy population and mean distance = 0.65 vs. 0.68 mm, maximum distance = 1.28 vs. 1.55 mm, time = 32 vs. 60 sec for the DCM population). A novel image straightening method that enables template-based analysis of quantitative spinal cord MRI data is introduced. This algorithm works for any MRI contrast and was validated on healthy and patient populations. The presented method is implemented in the Spinal Cord Toolbox, an open-source software for processing spinal cord MRI data. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1209-1219. © 2017 International Society for Magnetic Resonance in Medicine.

Clinical, magnetic resonance imaging, and histopathologic findings in 6 dogs with surgically resected extraparenchymal spinal cord hematomas.

PubMed

Hague, D W; Joslyn, S; Bush, W W; Glass, E N; Durham, A C

2015-01-01

Extraparenchymal spinal cord hematoma has been described in veterinary medicine in association with neoplasia, intervertebral disk disease, and snake envenomation. There are rare reports of spontaneous extraparenchymal spinal cord hematoma formation with no known cause in human medicine. Multiple cases of spontaneous extraparenchymal spinal cord hematoma have not been described previously in veterinary medicine. To describe the signalment, clinical findings, magnetic resonance imaging (MRI) features, and surgical outcomes in histopathologically confirmed extraparenchymal spinal cord hematomas in dogs with no identified underlying etiology. Six dogs had MRI of the spinal cord, decompressive spinal surgery, and histopathologic confirmation of extraparenchymal spinal cord hematoma not associated with an underlying cause. Multi-institutional retrospective study. Six patients had spontaneous extraparenchymal spinal cord hematoma formation. MRI showed normal signal within the spinal cord parenchyma in all patients. All hematomas had T2-weighted hyperintensity and the majority (5/6) had no contrast enhancement. All dogs underwent surgical decompression and most patients (5/6) returned to normal or near normal neurologic function postoperatively. Follow-up of the patients (ranging between 921 and 1,446 days) showed no progression of neurologic clinical signs or any conditions associated with increased bleeding tendency. Before surgery and histopathology confirming extraparenchymal hematoma, the primary differential in most cases was neoplasia, based on the MRI findings. This retrospective study reminds clinicians of the importance of the combination of advanced imaging combined with histopathologic diagnosis. The prognosis for spontaneous spinal cord extraparenchymal hematoma with surgical decompression appears to be favorable in most cases. Copyright © 2015 by the American College of Veterinary Internal Medicine.

Cytoarchitecture of the spinal cord of the postnatal (P4) mouse.

PubMed

Sengul, Gulgun; Puchalski, Ralph B; Watson, Charles

2012-05-01

Interpretation of the new wealth of gene expression and molecular mechanisms in the developing mouse spinal cord requires an accurate anatomical base on which data can be mapped. Therefore, we have assembled a spinal cord atlas of the P4 mouse to facilitate direct comparison with the adult specimens and to contribute to studies of the development of the mouse spinal cord. This study presents the anatomy of the spinal cord of the P4 C57Bl/6J mouse using Nissl and acetyl cholinesterase-stained sections. It includes a detailed map of the laminar organization of selected spinal cord segments and a description of named cell groups of the spinal cord such as the central cervical (CeCv), lateral spinal nucleus, lateral cervical, and dorsal nuclei. The motor neuron groups have also been identified according to the muscle groups they are likely to supply. General features of Rexed's laminae of the P4 spinal cord showed similarities to that of the adult (P56). However, certain differences were observed with regard to the extent of laminae and location of certain cell groups, such as the dorsal nucleus having a more dispersed structure and a more ventral and medial position or the CeCv being located in the medial part of lamina 5 in contrast to the adult where it is located in lamina 7. Motor neuron pools appeared to be more tightly packed in the P4 spinal cord. The dorsal horn was relatively larger and there was more white matter in the P56 spinal cord. Copyright © 2012 Wiley Periodicals, Inc.

Management of subaxial cervical facet dislocation through anterior approach monitored by spinal cord evoked potential.

PubMed

Du, Wei; Wang, Cheng; Tan, Jiangwei; Shen, Binghua; Ni, Shuqin; Zheng, Yanping

2014-01-01

Retrospective case series. To discuss the clinical efficacy of anterior cervical surgery of decompression, reduction, stabilization, and fusion in treating subaxial cervical facet dislocation without spinal cord injury or with mild spinal cord injury monitored by spinal cord evoked potential. The optimal treatment of lower cervical facet dislocation has been controversial. Because of the risk of iatrogenic damage of neurological function, it is challenging for surgeons to manage the lower cervical facet dislocation without or with mild spinal cord injury. To avoid the risks, more secure strategy need to be designed. A retrospective study was performed on 17 cases of subaxial cervical facet dislocation without spinal cord injury or with mild spinal cord injury treated by anterior cervical surgery under spinal cord evoked potential monitor from January 2008 to June 2012. There were 12 males, 5 females, with a mean age of 40.1 years (from 21 to 73 yr). Dislocation sites: 1 in C3-C4, 2 in C4-C5, 6 in C5-C6, 8 in C6-C7; 10 cases with unilateral cervical facet dislocation, 7 cases with bilateral dislocation. Thirteen patients were preoperatively classified as grade D and 4 as E according to Frankel standard. All patients were followed up for average of 16 months. All operations were completed successfully. Postoperative radiographs showed that the sequence and curvature of the cervical spine were well recovered. And, evidence of intervertebral fusion was observed at 3 months in all cases. No redislocation or symptoms of spinal cord injury occurred. Thirteen cases with mild spinal cord injury recovered at 1 month after operation. Anterior cervical surgery of decompression, reduction, stabilization, and fusion monitored by spinal cord evoked potential is an effective and safe method for treatment of subaxial cervical facet dislocation without or with mild spinal cord injury. 4.

General Information about Childhood Brain and Spinal Cord Tumors

MedlinePlus

... Cord Tumors Treatment Overview (PDQ®)–Patient Version General Information About Childhood Brain and Spinal Cord Tumors Go ... types of brain and spinal cord tumors. The information from tests and procedures done to detect (find) ...

The beneficial effects of treadmill step training on activity-dependent synaptic and cellular plasticity markers after complete spinal cord injury.

PubMed

Ilha, Jocemar; Centenaro, Lígia A; Broetto Cunha, Núbia; de Souza, Daniela F; Jaeger, Mariane; do Nascimento, Patrícia S; Kolling, Janaína; Ben, Juliana; Marcuzzo, Simone; Wyse, Angela T S; Gottfried, Carmem; Achaval, Matilde

2011-06-01

Several studies have shown that treadmill training improves neurological outcomes and promotes plasticity in lumbar spinal cord of spinal animals. The morphological and biochemical mechanisms underlying these phenomena remain unclear. The purpose of this study was to provide evidence of activity-dependent plasticity in spinal cord segment (L5) below a complete spinal cord transection (SCT) at T8-9 in rats in which the lower spinal cord segments have been fully separated from supraspinal control and that subsequently underwent treadmill step training. Five days after SCT, spinal animals started a step-training program on a treadmill with partial body weight support and manual step help. Hindlimb movements were evaluated over time and scored on the basis of the open-field BBB scale and were significantly improved at post-injury weeks 8 and 10 in trained spinal animals. Treadmill training also showed normalization of withdrawal reflex in trained spinal animals, which was significantly different from the untrained animals at post-injury weeks 8 and 10. Additionally, compared to controls, spinal rats had alpha motoneuronal soma size atrophy and reduced synaptophysin protein expression and Na(+), K(+)-ATPase activity in lumbar spinal cord. Step-trained rats had motoneuronal soma size, synaptophysin expression and Na(+), K(+)-ATPase activity similar to control animals. These findings suggest that treadmill step training can promote activity-dependent neural plasticity in lumbar spinal cord, which may lead to neurological improvements without supraspinal descending control after complete spinal cord injury.

Cellular Scaling Rules for Primate Spinal Cords

PubMed Central

Burish, Mark J.; Peebles, J. Klint; Baldwin, Mary K.; Tavares, Luciano; Kaas, Jon H.; Herculano-Houzel, Suzana

2010-01-01

The spinal cord can be considered a major sensorimotor interface between the body and the brain. How does the spinal cord scale with body and brain mass, and how are its numbers of neurons related to the number of neurons in the brain across species of different body and brain sizes? Here we determine the cellular composition of the spinal cord in eight primate species and find that its number of neurons varies as a linear function of cord length, and accompanies body mass raised to an exponent close to 1/3. This relationship suggests that the extension, mass and number of neurons that compose the spinal cord are related to body length, rather than to body mass or surface. Moreover, we show that although brain mass increases linearly with cord mass, the number of neurons in the brain increases with the number of neurons in the spinal cord raised to the power of 1.7. This faster addition of neurons to the brain than to the spinal cord is consistent with current views on how larger brains add complexity to the processing of environmental and somatic information. PMID:20926855

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

PubMed

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

2007-01-01

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

What Are the Key Statistics about Brain and Spinal Cord Cancers?

MedlinePlus

... Brain and Spinal Cord Tumors in Adults Key Statistics for Brain and Spinal Cord Tumors The American ... Cord Tumors . Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Written by References ...

Sildenafil effects on sexual and cardiovascular responses in women with spinal cord injury.

PubMed

Sipski, M L; Rosen, R C; Alexander, C J; Hamer, R M

2000-06-01

Sexual dysfunction is common in women with spinal cord injuries (SCIs) and other neurologic conditions. Sildenafil has previously been shown to be safe and effective in the treatment of erectile dysfunction due to SCI. This study is the first to evaluate the sexual and cardiovascular effects of sildenafil in women with SCIs in a controlled, laboratory setting. Nineteen premenopausal women with SCIs were randomly assigned to receive either sildenafil (50 mg) or placebo in a double-blind, crossover design study. Physiologic and subjective measures of sexual response, heart rate, and blood pressure were recorded during baseline and sexual stimulation conditions. Adverse events were also recorded. Significant increases in subjective arousal (SA) were observed with both drug (P <0.01) and sexual stimulation conditions (P <0.001), and a borderline significant (P <0.07) effect of drug administration on vaginal pulse amplitude (VPA) was noted. Maximal responses occurred when sildenafil was combined with visual and manual sexual stimulation. Cardiovascular data showed modest increases in heart rate (+/-5 bpm) and mild decreases in blood pressure (+/-4 mm Hg) across all stimulation conditions, consistent with the peripheral vasodilatory mechanism of the drug. Sildenafil was well tolerated with no evidence of significant adverse events. Findings suggest that sildenafil may partially reverse the sexual dysfunction commonly associated with SCI in women. Consistent with previous findings in men, the sexual effects of the drug were most evident under conditions of optimal stimulation. Mild, clinically insignificant cardiovascular effects were also noted. Further large-scale studies of sildenafil's effects in women with neurogenic sexual dysfunction are strongly indicated.

Perceptual Detection of Subtle Dysphonic Traits in Individuals with Cervical Spinal Cord Injury Using an Audience Response Systems Approach.

PubMed

Johansson, Kerstin; Strömbergsson, Sofia; Robieux, Camille; McAllister, Anita

2017-01-01

Reduced respiratory function following lower cervical spinal cord injuries (CSCIs) may indirectly result in vocal dysfunction. Although self-reports indicate voice change and limitations following CSCI, earlier efforts using global perceptual ratings to distinguish speakers with CSCI from noninjured speakers have not been very successful. We investigate the use of an audience response system-based approach to distinguish speakers with CSCI from noninjured speakers, and explore whether specific vocal traits can be identified as characteristic for speakers with CSCI. Fourteen speech-language pathologists participated in a web-based perceptual task, where their overt reactions to vocal dysfunction were registered during the continuous playback of recordings of 36 speakers (18 with CSCI, and 18 matched controls). Dysphonic events were identified through manual perceptual analysis, to allow the exploration of connections between dysphonic events and listener reactions. More dysphonic events, and more listener reactions, were registered for speakers with CSCI than for noninjured speakers. Strain (particularly in phrase-final position) and creak (particularly in nonphrase-final position) distinguish speakers with CSCI from noninjured speakers. For the identification of intermittent and subtle signs of vocal dysfunction, an approach where the temporal distribution of symptoms is registered offers a viable means to distinguish speakers affected by voice dysfunction from non-affected speakers. In speakers with CSCI, clinicians should listen for presence of final strain and nonfinal creak, and pay attention to self-reported voice function and voice problems, to identify individuals in need for clinical assessment and intervention. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

The spinal cord: a review of functional neuroanatomy.

PubMed

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

2013-02-01

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

Update on traumatic acute spinal cord injury. Part 2.

PubMed

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

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

Human iPS cell-derived astrocyte transplants preserve respiratory function after spinal cord injury

PubMed Central

Li, Ke; Javed, Elham; Scura, Daniel; Hala, Tamara J.; Seetharam, Suneil; Falnikar, Aditi; Richard, Jean-Philippe; Chorath, Ashley; Maragakis, Nicholas J.; Wright, Megan C.; Lepore, Angelo C.

2015-01-01

Transplantation-based replacement of lost and/or dysfunctional astrocytes is a promising therapy for spinal cord injury (SCI) that has not been extensively explored, despite the integral roles played by astrocytes in the central nervous system (CNS). Induced pluripotent stem (iPS) cells are a clinically-relevant source of pluripotent cells that both avoid ethical issues of embryonic stem cells and allow for homogeneous derivation of mature cell types in large quantities, potentially in an autologous fashion. Despite their promise, the iPS cell field is in its infancy with respect to evaluating in vivo graft integration and therapeutic efficacy in SCI models. Astrocytes express the major glutamate transporter, GLT1, which is responsible for the vast majority of glutamate uptake in spinal cord. Following SCI, compromised GLT1 expression/function can increase susceptibility to excitotoxicity. We therefore evaluated intraspinal transplantation of human iPS cell-derived astrocytes (hIPSAs) following cervical contusion SCI as a novel strategy for reconstituting GLT1 expression and for protecting diaphragmatic respiratory neural circuitry. Transplant-derived cells showed robust long-term survival post-injection and efficiently differentiated into astrocytes in injured spinal cord of both immunesuppressed mice and rats. However, the majority of transplant-derived astrocytes did not express high levels of GLT1, particularly at early times post-injection. To enhance their ability to modulate extracellular glutamate levels, we engineered hIPSAs with lentivirus to constitutively express GLT1. Overexpression significantly increased GLT1 protein and functional GLT1-mediated glutamate uptake levels in hIPSAs both in vitro and in vivo post-transplantation. Compared to human fibroblast control and unmodified hIPSA transplantation, GLT1-overexpressing hIPSAs reduced (1) lesion size within the injured cervical spinal cord, (2) morphological denervation by respiratory phrenic motor neurons at the diaphragm neuromuscular junction, and (3) functional diaphragm denervation as measured by recording of spontaneous EMGs and evoked compound muscle action potentials. Our findings demonstrate that hiPSA transplantation is a therapeutically-powerful approach for SCI. PMID:26216662

Human iPS cell-derived astrocyte transplants preserve respiratory function after spinal cord injury.

PubMed

Li, Ke; Javed, Elham; Scura, Daniel; Hala, Tamara J; Seetharam, Suneil; Falnikar, Aditi; Richard, Jean-Philippe; Chorath, Ashley; Maragakis, Nicholas J; Wright, Megan C; Lepore, Angelo C

2015-09-01

Transplantation-based replacement of lost and/or dysfunctional astrocytes is a promising therapy for spinal cord injury (SCI) that has not been extensively explored, despite the integral roles played by astrocytes in the central nervous system (CNS). Induced pluripotent stem (iPS) cells are a clinically-relevant source of pluripotent cells that both avoid ethical issues of embryonic stem cells and allow for homogeneous derivation of mature cell types in large quantities, potentially in an autologous fashion. Despite their promise, the iPS cell field is in its infancy with respect to evaluating in vivo graft integration and therapeutic efficacy in SCI models. Astrocytes express the major glutamate transporter, GLT1, which is responsible for the vast majority of glutamate uptake in spinal cord. Following SCI, compromised GLT1 expression/function can increase susceptibility to excitotoxicity. We therefore evaluated intraspinal transplantation of human iPS cell-derived astrocytes (hIPSAs) following cervical contusion SCI as a novel strategy for reconstituting GLT1 expression and for protecting diaphragmatic respiratory neural circuitry. Transplant-derived cells showed robust long-term survival post-injection and efficiently differentiated into astrocytes in injured spinal cord of both immunesuppressed mice and rats. However, the majority of transplant-derived astrocytes did not express high levels of GLT1, particularly at early times post-injection. To enhance their ability to modulate extracellular glutamate levels, we engineered hIPSAs with lentivirus to constitutively express GLT1. Overexpression significantly increased GLT1 protein and functional GLT1-mediated glutamate uptake levels in hIPSAs both in vitro and in vivo post-transplantation. Compared to human fibroblast control and unmodified hIPSA transplantation, GLT1-overexpressing hIPSAs reduced (1) lesion size within the injured cervical spinal cord, (2) morphological denervation by respiratory phrenic motor neurons at the diaphragm neuromuscular junction, and (3) functional diaphragm denervation as measured by recording of spontaneous EMGs and evoked compound muscle action potentials. Our findings demonstrate that hiPSA transplantation is a therapeutically-powerful approach for SCI. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of spinal cord level on sexual function in the spina bifida population.

PubMed

Lee, N G; Andrews, E; Rosoklija, I; Logvinenko, T; Johnson, E K; Oates, R D; Estrada, C R

2015-06-01

Sexual dysfunction and infertility are prevalent in the spina bifida (SB) population; however, the mechanism of how they affect a person with spina bifida is poorly understood. Additionally, the management of children with spina bifida becomes more difficult as they exit from pediatric institutes. The present study sought to evaluate sexual health (using validated questionnaires) and fertility in adults with spina bifida and to correlate spinal cord level and ambulatory status with degree of sexual function. After institutional board review approval, 199 adult patients with SB, aged 18 and older and who were followed in one pediatric institution, were identified. Patients who were non-English speaking, cognitively and/or developmentally delayed, or unable to be contacted were excluded. Surveys regarding demographics, sexual health and infertility were mailed to the patients and administered in the clinic with the option to opt-out of the survey. Survey questions regarding sexual health were constructed using validated questionnaires: Female Sexual Function Index (FSFI) for females, and International Index of Erectile Function (IIEF) and Sexual Health Inventory for Men (SHIM) for males. Sexual dysfunction scores were correlated to the patients' spinal level and ambulatory status. Of the 121 eligible patients, 45 replied, with a response rate of 39%. For females, using a cut-off value of 26.5 for FSFI scoring, 25 out of 28 (89%) had sexual dysfunction. No association was seen between spinal level or ambulatory status and overall FSFI, satisfaction, or desire scores. For males, 10 out of 17 (59%) had severe erectile dysfunction (ED), and one out of 17 (6%) had no ED. No association was seen between ambulatory status and sexual function scores for the males. However, SHIM, satisfaction, and ED scores were higher in males with lower spinal lesions. People with spina bifida of both genders tended to have more severe dysfunction compared to those with sexual dysfunction of other etiologies, except with similar sexual desire scores. Regarding questions on fertility, no participant attempted to have children; thus, there was no infertility reported. Few studies have been conducted on sexual health and fertility in adults with SB. Three studies have utilized validated questionnaires and found varying degrees of sexual dysfunction in this subset of patients; however, only one study found sexual activity to be more likely in patients with more caudal levels of neurologic impairment. The present study also showed that SHIM, satisfaction, and ED scores were higher in males with lower spinal lesions. Limitations to this study primarily included the small sample size and low survey response rate. Limited information is known about adults with SB, and sexual function and fertility. While expressing sexual desire, adults with SB appear to experience high rates of sexual dysfunction. Fertility rates were inadequately assessed; this was possibly due to the high rate of sexual dysfunction. Sexual health in the SB population is an important component of the myriad of urologic care issues for these people. Due to the disparity in their care after reaching adulthood, it is prudent to follow these patients and understand their pathophysiology as they continue to mature through life. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Imaging spinal cord atrophy in progressive myelopathies: HTLV-I-associated neurological disease (HAM/TSP) and multiple sclerosis (MS).

PubMed

Azodi, Shila; Nair, Govind; Enose-Akahata, Yoshimi; Charlip, Emily; Vellucci, Ashley; Cortese, Irene; Dwyer, Jenifer; Billioux, B Jeanne; Thomas, Chevaz; Ohayon, Joan; Reich, Daniel S; Jacobson, Steven

2017-11-01

Previous work measures spinal cord thinning in chronic progressive myelopathies, including human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and multiple sclerosis (MS). Quantitative measurements of spinal cord atrophy are important in fully characterizing these and other spinal cord diseases. We aimed to investigate patterns of spinal cord atrophy and correlations with clinical markers. Spinal cord cross-sectional area was measured in individuals (24 healthy controls [HCs], 17 asymptomatic carriers of HTLV-1 (AC), 47 HAM/TSP, 74 relapsing-remitting MS [RRMS], 17 secondary progressive MS [SPMS], and 40 primary progressive MS [PPMS]) from C1 to T10. Clinical disability scores, viral markers, and immunological parameters were obtained for patients and correlated with representative spinal cord cross-sectional area regions at the C2 to C3, C4 to C5, and T4 to T9 levels. In 2 HAM/TSP patients, spinal cord cross-sectional area was measured over 3 years. All spinal cord regions are thinner in HAM/TSP (56 mm 2 [standard deviation, 10], 59 [10], 23 [5]) than in HC (76 [7], 83 [8], 38 [4]) and AC (71 [7], 78 [9], 36 [7]). SPMS (62 [9], 66 [9], 32 [6]) and PPMS (65 [11], 68 [10], 35 [7]) have thinner cervical cords than HC and RRMS (73 [9], 77 [10], 37 [6]). Clinical disability scores (Expanded Disability Status Scale [p = 0.009] and Instituto de Pesquisas de Cananeia [p = 0.03]) and CD8 + T-cell frequency (p = 0.04) correlate with T4 to T9 spinal cord cross-sectional area in HAM/TSP. Higher cerebrospinal fluid HTLV-1 proviral load (p = 0.01) was associated with thinner spinal cord cross-sectional area. Both HAM/TSP patients followed longitudinally showed thoracic thinning followed by cervical thinning. Group average spinal cord cross-sectional area in HAM/TSP and progressive MS show spinal cord atrophy. We further hypothesize in HAM/TSP that is possible that neuroglial loss from a thoracic inflammatory process results in anterograde and retrograde degeneration of axons, leading to the temporal progression of thoracic to cervical atrophy described here. Ann Neurol 2017;82:719-728. © 2017 American Neurological Association.

Migration of luque rods through a laminectomy defect causing spinal cord compression.

PubMed

Quint, D J; Salton, G

1993-01-01

Internal fixation of traumatic spinal injuries has been associated with spinal canal stenosis, spinal cord compression, and nerve root impingement. We present a case of spinal cord/cauda equina compression due to migration of intact, anchored thoracolumbar Luque rods into the spinal canal through a laminectomy defect, leading to neurologic complications 10 years after the original operation.

[Persistent Bilateral Vocal Cord Paralysis after General Anesthesia in a Patient with Multiple System Atrophy: A Case Report].

PubMed

Konishi, Hanako; Mizota, Toshiyuki; Fukuda, Kazuhiko

2015-06-01

We report a case of persistent bilateral vocal cord paralysis which developed after spine surgery under general anesthesia in a patient with multiple system atrophy. A 64-year-old woman was scheduled to receive spinal fusion surgery for kyphoscoliosis. She did not have apparent symptoms of vocal cord paralysis such as hoarseness before surgery. The surgery was performed smoothly under general anesthesia with endotracheal intubation. However, immediately after extubation, the patient developed severe upper airway obstruction and was re-intubated. Fiberoptic laryngoscopy revealed bilateral vocal cord abductor paralysis. Vocal cord paralysis did not improve and she received tracheotomy on the 12th day after surgery. She also showed symptoms of autonomic nervous system dysfunction and cerebellar ataxia, and was diagnosed as multiple system atrophy on postoperative day 64. We discuss differential diagnosis of persistent vocal cord paralysis after general anesthesia, and anesthetic management of a patient with multiple system atrophy.

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

PubMed

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

2006-01-01

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

Long-Term Extensive Ectopic Hair Growth on the Spinal Cord of Mice from Transplanted Whisker Follicles.

PubMed

Cao, Wenluo; Li, Lingna; Mii, Sumiyuki; Amoh, Yasuyuki; Liu, Fang; Hoffman, Robert M

2015-01-01

We have previously demonstrated that hair follicles contain nestin-expressing pluripotent stem cells that can effect nerve and spinal cord repair upon transplantation. In the present study, isolated whisker follicles from nestin-driven green fluorescent protein (ND-GFP) mice were histocultured on Gelfoam for 3 weeks for the purpose of transplantation to the spinal cord to heal an induced injury. The hair shaft was cut off from Gelfoam-histocultured whisker follicles, and the remaining part of the whisker follicles containing GFP-nestin expressing pluripotent stem cells were transplanted into the injured spinal cord of nude mice, along with the Gelfoam. After 90 days, the mice were sacrificed and the spinal cord lesion was observed to have healed. ND-GFP expression was intense at the healed area of the spinal cord, as observed by fluorescence microscopy, demonstrating that the hair follicle stem cells were involved in healing the spinal cord. Unexpectedly, the transplanted whisker follicles sprouted out remarkably long hair shafts in the spinal cord during the 90 days after transplantation of Gelfoam whisker histocultures to the injured spine. The pigmented hair fibers, grown from the transplanted whisker histocultures, curved and enclosed the spinal cord. The unanticipated results demonstrate the great potential of hair growth after transplantation of Gelfoam hair follicle histocultures, even at an ectopic site.

Spinal cord stimulation for refractory angina in a patient implanted with a cardioverter defibrillator.

PubMed

Ferrero, Paolo; Grimaldi, Roberto; Massa, Riccardo; Chiribiri, Amedeo; De Luca, Anna; Castellano, Maddalena; Cardano, Paola; Trevi, Gian Paolo

2007-01-01

Spinal cord stimulation is currently used to treat refractory angina. Some concerns may arise about the possible interaction concerning the spinal cord stimulator in patients already implanted with a pacemaker or a cardioverter defibrillator. We are going to describe the successful implantation of a spinal cord stimulator in a patient previously implanted with a cardioverter defibrillator.

Spinal cord stress injury assessment (SCOSIA): clinical applications of mechanical modeling of the spinal cord and brainstem

NASA Astrophysics Data System (ADS)

Wong, Kenneth H.; Choi, Jae; Wilson, William; Berry, Joel; Henderson, Fraser C., Sr.

2009-02-01

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.

Effects of vertebral column distraction on transcranial electrical stimulation-motor evoked potential and histology of the spinal cord in a porcine model.

PubMed

Yang, Jae Hyuk; Suh, Seung Woo; Modi, Hitesh N; Ramani, Easwar T; Hong, Jae Young; Hwang, Jin Ho; Jung, Woon Yong

2013-05-01

Spinal cord injury can occur following surgical procedures for correction of scoliosis and kyphosis, as these procedures produce lengthening of the vertebral column. The objective of this study was to cause spinal cord injury by vertebral column distraction and evaluate the histological changes in the spinal cord in relationship to the pattern of recovery from the spinal cord injury. Global osteotomy of all three spinal columns was performed on the ninth thoracic vertebra of sixteen pigs. The osteotomized vertebra was distracted until transcranial electrical stimulation-motor evoked potential (TES-MEP) signals disappeared or decreased by >80% compared with the baseline amplitude; this was defined as spinal cord injury. The distraction distance at which spinal cord injury occurred was measured, the distraction was released, and the TES-MEP recovery pattern was observed. A wake-up test was performed, two days of observations were made, and histological changes were evaluated in relationship to the recovery pattern. Spinal cord injury developed at a distraction distance of 20.2 ± 4.7 mm, equivalent to 3.6% of the thoracolumbar spinal length, and the distraction distance was correlated with the thoracolumbar spinal length (r = 0.632, p = 0.009). No animals exhibited complete recovery according to TES-MEP testing, eleven exhibited incomplete recovery, and five exhibited no recovery. During the two days of observation, all eleven animals with incomplete recovery showed positive responses to sensory and motor tests, whereas none of the five animals with no recovery had positive responses. On histological evaluation, three animals that exhibited no recovery all showed complete severance of nerve fibers (axotomy), whereas six animals that exhibited incomplete recovery all showed partial white-matter injury. Parallel distraction of approximately 3.6% of the thoracolumbar length after global osteotomy resulted in spinal cord injury and histological evidence of spinal cord damage. The pattern of recovery from the spinal cord injury after release of the distraction was consistent with the degree of axonal damage. Axotomy was observed in animals that exhibited no recovery on TES-MEP, and only hemorrhagic changes in the white matter were observed in animals that exhibited incomplete recovery.

Exploration of Spinal Cord Aging–Related Proteins Using a Proteomics Approach

PubMed Central

Kamiya, Koshiro; Furuya, Takeo; Hashimoto, Masayuki; Mannoji, Chikato; Inada, Taigo; Ota, Mitsutoshi; Maki, Satoshi; Ijima, Yasushi; Saito, Junya; Kitamura, Mitsuhiro; Ohtori, Seiji; Orita, Sumihisa; Inage, Kazuhide; Yamazaki, Masashi; Koda, Masao

2017-01-01

How aging affects the spinal cord at a molecular level is unclear. The aim of this study was to explore spinal cord aging–related proteins that may be involved in pathological mechanisms of age-related changes in the spinal cord. Spinal cords of 2-year-old and 8-week-old female Sprague-Dawley rats were dissected from the animals. Protein samples were subjected to 2-dimentional polyacrylamide gel electrophoresis followed by mass spectrometry. Screened proteins were further investigated with immunohistochemistry and Western blotting. Among the screened proteins, we selected α-crystallin B-subunit (αB-crystallin) and peripherin for further investigation because these proteins were previously reported to be related to central nervous system pathologies. Immunohistochemistry and Western blotting revealed significant upregulation of αB-crystallin and peripherin expression in aged rat spinal cord. Further exploration is needed to elucidate the precise mechanism and potential role of these upregulated proteins in spinal cord aging processes. PMID:28634429

Is neuroinflammation in the injured spinal cord different than in the brain? Examining intrinsic differences between the brain and spinal cord.

PubMed

Zhang, B; Gensel, J C

2014-08-01

The field of neuroimmunology is rapidly advancing. There is a growing appreciation for heterogeneity, both in inflammatory composition and region-specific inflammatory responses. This understanding underscores the importance of developing targeted immunomodulatory therapies for treating neurological disorders. Concerning neurotrauma, there is a dearth of publications directly comparing inflammatory responses in the brain and spinal cord after injury. The question therefore remains as to whether inflammatory cells responding to spinal cord vs. brain injury adopt similar functions and are therefore amenable to common therapies. In this review, we address this question while revisiting and modernizing the conclusions from publications that have directly compared inflammation across brain and spinal cord injuries. By examining molecular differences, anatomical variations, and inflammatory cell phenotypes between the injured brain and spinal cord, we provide insight into how neuroinflammation relates to neurotrauma and into fundamental differences between the brain and spinal cord. Copyright © 2014 Elsevier Inc. All rights reserved.

Functional characterization of mouse spinal cord infiltrating CD8+ lymphocytes

PubMed Central

Deb, Chandra; Howe, Charles L

2011-01-01

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

Plasticity and regeneration in the injured spinal cord after cell transplantation therapy.

PubMed

Nori, Satoshi; Nakamura, Masaya; Okano, Hideyuki

2017-01-01

Spinal cord injury (SCI) typically damages the long axonal tracts of the spinal cord which results in permanent disability. However, regeneration of the injured spinal cord is approaching reality according to the advances in stem cell biology. Cell transplantation therapy holds potential to lead to recovery following SCI through some positive mechanisms. Grafted cells induce plasticity and regeneration in the injured spinal cord by promoting remyelination of damaged axons, reconstruction of neural circuits by synapse formation between host neurons and graft-derived neurons, and secreting neurotrophic factors to promote axonal elongation as well as reduce retrograde axonal degeneration. In this review, we will delineate (1) the microenvironment of the injured spinal cord that influence the plasticity and regeneration capacity after SCI, (2) a number of different kinds of cell transplantation therapies for SCI that has been extensively studied by researchers, and (3) potential mechanisms of grafted cell-induced regeneration and plasticity in the injured spinal cord. © 2017 Elsevier B.V. All rights reserved.

Naturally Occurring Disk Herniation in Dogs: An Opportunity for Pre-Clinical Spinal Cord Injury Research

PubMed Central

Levine, Gwendolyn J.; Porter, Brian F.; Topp, Kimberly; Noble-Haeusslein, Linda J.

2011-01-01

Abstract Traumatic spinal cord injuries represent a significant source of morbidity in humans. Despite decades of research using experimental models of spinal cord injury to identify candidate therapeutics, there has been only limited progress toward translating beneficial findings to human spinal cord injury. Thoracolumbar intervertebral disk herniation is a naturally occurring disease that affects dogs and results in compressive/contusive spinal cord injury. Here we discuss aspects of this disease that are analogous to human spinal cord injury, including injury mechanisms, pathology, and metrics for determining outcomes. We address both the strengths and weaknesses of conducting pre-clinical research in these dogs, and include a review of studies that have utilized these animals to assess efficacy of candidate therapeutics. Finally, we consider a two-species approach to pre-clinical data acquisition, beginning with a reproducible model of spinal cord injury in the rodent as a tool for discovery with validation in pet dogs with intervertebral disk herniation. PMID:21438715

Quantitative measurement of intervertebral disc signal using MRI.

PubMed

Niemeläinen, R; Videman, T; Dhillon, S S; Battié, M C

2008-03-01

To investigate the spinal cord as an alternative intra-body reference to cerebrospinal fluid (CSF) in evaluating thoracic disc signal intensity. T2-weighted magnetic resonance imaging (MRI) images of T6-T12 were obtained using 1.5 T machines for a population-based sample of 523 men aged 35-70 years. Quantitative data on the signal intensities were acquired using an image analysis program (SpEx). A random sample of 30 subjects and intraclass correlation coefficients (ICC) were used to examine the repeatability of the spinal cord measurements. The validity of using the spinal cord as a reference was examined by correlating cord and CSF samples. Finally, thoracic disc signal was validated by correlating it with age without adjustment and adjusting for either cord or CSF. Pearson's r was used for correlational analyses. The repeatability of the spinal cord signal measurements was extremely high (>or=0.99). The correlations between the signals of spinal cord and CSF by level were all above 0.9. The spinal cord-adjusted disc signal and age correlated similarly with CSF-adjusted disc signal and age (r=-0.30 to -0.40 versus r=-0.26 to -0.36). Adjacent spinal cord is a good alternative reference to the current reference standard, CSF, for quantitative measurements of disc signal intensity. Clearly fewer levels were excluded when using spinal cord as compared to CSF due to missing reference samples.

Magnetic resonance imaging tractography as a diagnostic tool in patients with spinal cord injury treated with human embryonic stem cells.

PubMed

Shroff, Geeta

2017-02-01

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.

Cervical spinal stenosis and sports-related cervical cord neurapraxia in children.

PubMed

Boockvar, J A; Durham, S R; Sun, P P

2001-12-15

Congenital spinal stenosis has been demonstrated to contribute to cervical cord neurapraxia after cervical spinal cord injury in adult athletes. A sagittal canal diameter <14 mm and/or a Torg ratio (sagittal diameter of the spinal canal: midcervical sagittal vertebral body diameter) of <0.8 are indicative of significant cervical spinal stenosis. Although sports-related cervical spine injuries are common in children, the role of congenital cervical stenosis in the etiology of these injuries remains unclear. The authors measured the sagittal canal diameter and the Torg ratio in children presenting with cervical cord neurapraxia resulting from sports-related cervical spinal cord injuries to determine the presence of congenital spinal stenosis. A total of 13 children (9 male, 4 female) presented with cervical cord neurapraxia after a sports-related cervical spinal cord injury. Age ranged from 7 to 15 years (mean +/- SD, 11.5 +/- 2.7 years). The sports involved were football (n = 4), wrestling (n = 2), hockey (n = 2), and soccer, gymnastics, baseball, kickball, and pogosticking (n = 1 each). Lateral cervical spine radiographs were used to determine the sagittal canal diameter and the Torg ratio at C4. The sagittal canal diameter (mean +/- SD, 17.58 +/- 1.63 mm) and the Torg ratio (mean +/- SD, 1.20 +/- 0.24) were normal in all of these children. Using the sagittal canal diameter and the Torg ratio as a measurement of congenital spinal stenosis, the authors did not find evidence of congenital cervical spinal stenosis in a group of children with sports-related cervical spinal cord neurapraxia. The occurrence of cervical cord neurapraxia in pediatric patients can be attributed to the mobility of the pediatric spine rather than to congenital cervical spinal stenosis.

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

PubMed

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

2010-03-17

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

Recurrent ‘universal tumour’ of the spinal cord

PubMed Central

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

2012-01-01

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

Electronic bypass of spinal lesions: activation of lower motor neurons directly driven by cortical neural signals.

PubMed

Li, Yan; Alam, Monzurul; Guo, Shanshan; Ting, K H; He, Jufang

2014-07-03

Lower motor neurons in the spinal cord lose supraspinal inputs after complete spinal cord injury, leading to a loss of volitional control below the injury site. Extensive locomotor training with spinal cord stimulation can restore locomotion function after spinal cord injury in humans and animals. However, this locomotion is non-voluntary, meaning that subjects cannot control stimulation via their natural "intent". A recent study demonstrated an advanced system that triggers a stimulator using forelimb stepping electromyographic patterns to restore quadrupedal walking in rats with spinal cord transection. However, this indirect source of "intent" may mean that other non-stepping forelimb activities may false-trigger the spinal stimulator and thus produce unwanted hindlimb movements. We hypothesized that there are distinguishable neural activities in the primary motor cortex during treadmill walking, even after low-thoracic spinal transection in adult guinea pigs. We developed an electronic spinal bridge, called "Motolink", which detects these neural patterns and triggers a "spinal" stimulator for hindlimb movement. This hardware can be head-mounted or carried in a backpack. Neural data were processed in real-time and transmitted to a computer for analysis by an embedded processor. Off-line neural spike analysis was conducted to calculate and preset the spike threshold for "Motolink" hardware. We identified correlated activities of primary motor cortex neurons during treadmill walking of guinea pigs with spinal cord transection. These neural activities were used to predict the kinematic states of the animals. The appropriate selection of spike threshold value enabled the "Motolink" system to detect the neural "intent" of walking, which triggered electrical stimulation of the spinal cord and induced stepping-like hindlimb movements. We present a direct cortical "intent"-driven electronic spinal bridge to restore hindlimb locomotion after complete spinal cord injury.

Neuropeptide Y in human spinal cord.

PubMed

Allen, J M; Gibson, S J; Adrian, T E; Polak, J M; Bloom, S R

1984-08-06

The distribution of a newly described peptide, neuropeptide Y (NPY) within the human spinal cord has been determined using radioimmunoassay and immunocytochemistry. Higher concentrations were found in the lumbar (49.9 +/- 6.8 pmol/g) and sacral (47.0 +/- 10.6 pmol/g) regions than in the cervical (27.6 +/- 2.7 pmol/g) and thoracic spinal cord (33.8 +/- 5.3 pmol/g). Immunocytochemistry revealed numerous nerve fibers containing NPY in the spinal cord; these were particularly concentrated in the substantia gelatinosa of the dorsal horn. In the ventral spinal cord NPY-containing nerves were sparse becoming more abundant in lumbosacral segments.

Early changes in muscle atrophy and muscle fiber type conversion after spinal cord transection and peripheral nerve transection in rats.

PubMed

Higashino, Kosaku; Matsuura, Tetsuya; Suganuma, Katsuyoshi; Yukata, Kiminori; Nishisho, Toshihiko; Yasui, Natsuo

2013-05-20

Spinal cord transection and peripheral nerve transection cause muscle atrophy and muscle fiber type conversion. It is still unknown how spinal cord transection and peripheral nerve transection each affect the differentiation of muscle fiber type conversion mechanism and muscle atrophy. The aim of our study was to evaluate the difference of muscle weight change, muscle fiber type conversion, and Peroxisome proliferator-activated receptor-γ coactivatior-1α (PGC-1α) expression brought about by spinal cord transection and by peripheral nerve transection. Twenty-four Wistar rats underwent surgery, the control rats underwent a laminectomy; the spinal cord injury group underwent a spinal cord transection; the denervation group underwent a sciatic nerve transection. The rats were harvested of the soleus muscle and the TA muscle at 0 week, 1 week and 2 weeks after surgery. Histological examination was assessed using hematoxylin and eosin (H&E) staining and immunofluorescent staing. Western blot was performed with 3 groups. Both sciatic nerve transection and spinal cord transection caused muscle atrophy with the effect being more severe after sciatic nerve transection. Spinal cord transection caused a reduction in the expression of both sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection produced an increase in expression of sMHC protein and PGC-1α protein in the soleus muscle. The results of the expression of PGC-1α were expected in other words muscle atrophy after sciatic nerve transection is less than after spinal cord transection, however muscle atrophy after sciatic nerve transection was more severe than after spinal cord transection. In the conclusion, spinal cord transection diminished the expression of sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection enhanced the expression of sMHC protein and PGC-1α protein in the soleus muscle.

Neurotrophic factors and receptors in the immature and adult spinal cord after mechanical injury or kainic acid.

PubMed

Widenfalk, J; Lundströmer, K; Jubran, M; Brene, S; Olson, L

2001-05-15

Delivery of neurotrophic factors to the injured spinal cord has been shown to stimulate neuronal survival and regeneration. This indicates that a lack of sufficient trophic support is one factor contributing to the absence of spontaneous regeneration in the mammalian spinal cord. Regulation of the expression of neurotrophic factors and receptors after spinal cord injury has not been studied in detail. We investigated levels of mRNA-encoding neurotrophins, glial cell line-derived neurotrophic factor (GDNF) family members and related receptors, ciliary neurotrophic factor (CNTF), and c-fos in normal and injured spinal cord. Injuries in adult rats included weight-drop, transection, and excitotoxic kainic acid delivery; in newborn rats, partial transection was performed. The regulation of expression patterns in the adult spinal cord was compared with that in the PNS and the neonate spinal cord. After mechanical injury of the adult rat spinal cord, upregulations of NGF and GDNF mRNA occurred in meningeal cells adjacent to the lesion. BDNF and p75 mRNA increased in neurons, GDNF mRNA increased in astrocytes close to the lesion, and GFRalpha-1 and truncated TrkB mRNA increased in astrocytes of degenerating white matter. The relatively limited upregulation of neurotrophic factors in the spinal cord contrasted with the response of affected nerve roots, in which marked increases of NGF and GDNF mRNA levels were observed in Schwann cells. The difference between the ability of the PNS and CNS to provide trophic support correlates with their different abilities to regenerate. Kainic acid delivery led to only weak upregulations of BDNF and CNTF mRNA. Compared with several brain regions, the overall response of the spinal cord tissue to kainic acid was weak. The relative sparseness of upregulations of endogenous neurotrophic factors after injury strengthens the hypothesis that lack of regeneration in the spinal cord is attributable at least partly to lack of trophic support.

Living with Spinal Cord Injury

MedlinePlus

... With Spinal Cord Injury A spinal cord injury (SCI) can result from trauma, such as a motor ... these injuries occur in men. A person with SCI typically has some paralysis and decreased or loss ...

Right-sided vagus nerve stimulation inhibits induced spinal cord seizures.

PubMed

Tubbs, R Shane; Salter, E George; Killingsworth, Cheryl; Rollins, Dennis L; Smith, William M; Ideker, Raymond E; Wellons, John C; Blount, Jeffrey P; Oakes, W Jerry

2007-01-01

We have previously shown that left-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. To test our hypothesis that right-sided vagus nerve stimulation will also abort seizure activity, we have initiated seizures in the spinal cord and then performed right-sided vagus nerve stimulation in an animal model. Four pigs were anesthetized and placed in the lateral position and a small laminectomy performed in the lumbar region. Topical penicillin, a known epileptogenic drug to the cerebral cortex and spinal cord, was next applied to the dorsal surface of the exposed cord. With the exception of the control animal, once seizure activity was discernible via motor convulsion or increased electrical activity, the right vagus nerve previously isolated in the neck was stimulated. Following multiple stimulations of the vagus nerve and with seizure activity confirmed, the cord was transected in the midthoracic region and vagus nerve stimulation performed. Right-sided vagus nerve stimulation resulted in cessation of spinal cord seizure activity in all animals. Transection of the spinal cord superior to the site of seizure induction resulted in the ineffectiveness of vagus nerve stimulation in causing cessation of seizure activity in all study animals. As with left-sided vagus nerve stimulation, right-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. Additionally, the effects of right-sided vagus nerve stimulation on induced spinal cord seizures involve descending spinal pathways. These data may aid in the development of alternative mechanisms for electrical stimulation for patients with medically intractable seizures and add to our knowledge regarding the mechanism for seizure cessation following peripheral nerve stimulation.

Spectrum of Spinal Cord, Spinal Root, and Brain MRI Abnormalities in Congenital Zika Syndrome with and without Arthrogryposis.

PubMed

Aragao, M F V V; Brainer-Lima, A M; Holanda, A C; van der Linden, V; Vasco Aragão, L; Silva Júnior, M L M; Sarteschi, C; Petribu, N C L; Valença, M M

2017-05-01

Arthrogryposis is among the malformations of congenital Zika syndrome. Similar to the brain, there might exist a spectrum of spinal cord abnormalities. The purpose of this study was to explore and describe in detail the MR imaging features found in the spinal cords, nerve roots, and brains of children with congenital Zika syndrome with and without arthrogryposis. Twelve infants with congenital Zika syndrome (4 with arthrogryposis and 8 without) who had undergone brain and spinal cord MR imaging were retrospectively selected. Qualitative and quantitative analyses were performed and compared between groups. At visual inspection, both groups showed reduced thoracic spinal cord thickness: 75% (6/8) of the group without arthrogryposis and 100% (4/4) of the arthrogryposis group. However, the latter had the entire spinal cord reduced and more severely reduced conus medullaris anterior roots (respectively, P = .002 and .007). Quantitative differences were found for conus medullaris base and cervical and lumbar intumescences diameters (respectively, P = .008, .048, .008), with more prominent reduction in arthrogryposis. Periventricular calcifications were more frequent in infants with arthrogryposis ( P = .018). Most infants had some degree of spinal cord thickness reduction, predominant in the thoracic segment (without arthrogryposis) or in the entire spinal cord (with arthrogryposis). The conus medullaris anterior roots were reduced in both groups (thinner in arthrogryposis). A prominent anterior median fissure of the spinal cord was absent in infants without arthrogryposis. Brain stem hypoplasia was present in all infants with arthrogryposis, periventricular calcifications, in the majority, and polymicrogyria was absent. © 2017 by American Journal of Neuroradiology.

The current state-of-the-art of spinal cord imaging: Methods

PubMed Central

Stroman, P.W.; Wheeler-Kingshott, C.; Bacon, M.; Schwab, J.M.; Bosma, R.; Brooks, J.; Cadotte, D.; Carlstedt, T.; Ciccarelli, O.; Cohen-Adad, J.; Curt, A.; Evangelou, N.; Fehlings, M.G.; Filippi, M.; Kelley, B.J.; Kollias, S.; Mackay, A.; Porro, C.A.; Smith, S.; Strittmatter, S.M.; Summers, P.; Tracey, I.

2015-01-01

A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small cross-sectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of “critical mass” of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researchers to create the necessary scientific and clinical network to advance the rate of progress and impact of the research. PMID:23685159

Spinal cord injury - Symptoms and causes

MedlinePlus

... are the leading cause of spinal cord injuries, accounting for almost half of new spinal cord injuries ... address these problems if they affect you. Respiratory system. Your injury may make it more difficult to ...

In silico modeling of axonal reconnection within a discrete fiber tract after spinal cord injury.

PubMed

Woolfe, Franco; Waxman, Stephen G; Hains, Bryan C

2007-02-01

Following spinal cord injury (SCI), descending axons that carry motor commands from the brain to the spinal cord are injured or transected, producing chronic motor dysfunction and paralysis. Reconnection of these axons is a major prerequisite for restoration of function after SCI. Thus far, only modest gains in motor function have been achieved experimentally or in the clinic after SCI, identifying the practical limitations of current treatment approaches. In this paper, we use an ordinary differential equation (ODE) to simulate the relative and synergistic contributions of several experimentally-established biological factors related to inhibition or promotion of axonal repair and restoration of function after SCI. The factors were mathematically modeled by the ODE. The results of our simulation show that in a model system, many factors influenced the achievability of axonal reconnection. Certain factors more strongly affected axonal reconnection in isolation, and some factors interacted in a synergistic fashion to produce further improvements in axonal reconnection. Our data suggest that mathematical modeling may be useful in evaluating the complex interactions of discrete therapeutic factors not possible in experimental preparations, and highlight the benefit of a combinatorial therapeutic approach focused on promoting axonal sprouting, attraction of cut ends, and removal of growth inhibition for achieving axonal reconnection. Predictions of this simulation may be of utility in guiding future experiments aimed at restoring function after SCI.

IGF-1 and BDNF promote chick bulbospinal neurite outgrowth in vitro.

PubMed

Salie, Rishard; Steeves, John D

2005-11-01

Injured neurons in the CNS do not experience significant functional regeneration and so spinal cord insult often results in permanently compromised locomotor ability. The capability of a severed axon to re-grow is thought to depend on numerous factors, one of which is the decreased availability of neurotrophic factors. Application of trophic factors to axotomized neurons has been shown to enhance survival and neurite outgrowth. Although brainstem-spinal connections play a pivotal role in motor dysfunction after spinal cord injury, relatively little is known about the trophic sensitivity of these populations. This study explores the response of bulbospinal populations to various trophic factors. Several growth factors were initially examined for potential trophic effects on the projection neurons of the brainstem. Brain derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF-1) significantly enhance mean process length in both the vestibulospinal neurons and spinal projection neurons from the raphe nuclei. Nerve growth factor (NGF), neurotrophin-4 (NT-4) and glial derived neurotrophic factor (GDNF) did not effect process outgrowth in vestibulospinal neurons. At the developmental stages used in this study, it was determined that receptors for BDNF and IGF-1 were present both on bulbospinal neurons and on surrounding cells with a non-neuronal morphology.

Griffonia simplicifolia Isolectin B4 Identifies a Specific Subpopulation of Angiogenic Blood Vessels Following Contusive Spinal Cord Injury in the Adult Mouse

PubMed Central

BENTON, RICHARD L.; MADDIE, MELISSA A.; MINNILLO, DANIELLE R.; HAGG, THEO; WHITTEMORE, SCOTT R.

2009-01-01

After traumatic spinal cord injury (SCI), disruption and plasticity of the microvasculature within injured spinal tissue contribute to the pathological cascades associated with the evolution of both primary and secondary injury. Conversely, preserved vascular function most likely results in tissue sparing and subsequent functional recovery. It has been difficult to identify subclasses of damaged or regenerating blood vessels at the cellular level. Here, adult mice received a single intravenous injection of the Griffonia simplicifolia isolectin B4 (IB4) at 1–28 days following a moderate thoracic (T9) contusion. Vascular binding of IB4 was maximally observed 7 days following injury, a time associated with multiple pathologic aspects of the intrinsic adaptive angiogenesis, with numbers of IB4 vascular profiles decreasing by 21 days postinjury. Quantitative assessment of IB4 binding shows that it occurs within the evolving lesion epicenter, with affected vessels expressing a temporally specific dysfunctional tight junctional phenotype as assessed by occludin, claudin-5, and ZO-1 immunoreactivities. Taken together, these results demonstrate that intravascular lectin delivery following SCI is a useful approach not only for observing the functional status of neovascular formation but also for definitively identifying specific subpopulations of reactive spinal microvascular elements. PMID:18092342

Astrocytes influence the severity of spinal muscular atrophy

PubMed Central

Rindt, Hansjörg; Feng, Zhihua; Mazzasette, Chiara; Glascock, Jacqueline J.; Valdivia, David; Pyles, Noah; Crawford, Thomas O.; Swoboda, Kathryn J.; Patitucci, Teresa N.; Ebert, Allison D.; Sumner, Charlotte J.; Ko, Chien-Ping; Lorson, Christian L.

2015-01-01

Systemically low levels of survival motor neuron-1 (SMN1) protein cause spinal muscular atrophy (SMA). α-Motor neurons of the spinal cord are considered particularly vulnerable in this genetic disorder and their dysfunction and loss cause progressive muscle weakness, paralysis and eventually premature death of afflicted individuals. Historically, SMA was therefore considered a motor neuron-autonomous disease. However, depletion of SMN in motor neurons of normal mice elicited only a very mild phenotype. Conversely, restoration of SMN to motor neurons in an SMA mouse model had only modest effects on the SMA phenotype and survival. Collectively, these results suggested that additional cell types contribute to the pathogenesis of SMA, and understanding the non-autonomous requirements is crucial for developing effective therapies. Astrocytes are critical for regulating synapse formation and function as well as metabolic support for neurons. We hypothesized that astrocyte functions are disrupted in SMA, exacerbating disease progression. Using viral-based restoration of SMN specifically to astrocytes, survival in severe and intermediate SMA mice was observed. In addition, neuromuscular circuitry was improved. Astrogliosis was prominent in end-stage SMA mice and in post-mortem patient spinal cords. Increased expression of proinflammatory cytokines was partially normalized in treated mice, suggesting that astrocytes contribute to the pathogenesis of SMA. PMID:25911676

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

PubMed

Naess, Halvor; Romi, Fredrik

2011-01-01

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

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

PubMed Central

Naess, Halvor; Romi, Fredrik

2011-01-01

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

21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted spinal cord stimulator for bladder evacuation. 882.5850 Section 882.5850 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal...

21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted spinal cord stimulator for bladder evacuation. 882.5850 Section 882.5850 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal...

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

PubMed

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

2018-05-14

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

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

PubMed Central

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

2014-01-01

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

(18)F-FDG uptake of the spinal cord was decreased after conventional dose radiotherapy in esophageal cancer patients.

PubMed

Harata, Naoki; Yoshida, Katsuya; Oota, Sayako; Fujii, Hayahiko; Isogai, Jun; Yoshimura, Ryoichi

2016-01-01

We retrospectively investigated changes of (18)F-fluorodeocyglucose ((18)F-FDG) uptake in the spinal cord, inside and outside the radiation fields, in patients with esophageal cancer before and after conventional dose radiotherapy. A total of 17 consecutive patients with esophageal cancer (16 males, one female; age 50-83 years, mean 67.0 years), who underwent conventional dose radiotherapy and (18)F-FDG PET/CT before and 5.1 months (range 1.6-8.6 months) after the radiotherapy, were retrospectively evaluated. Sixteen patients had esophageal cancer and one patient had esophageal metastasis from thyroid cancer. Mean standardized uptake values (SUVmean) of the cervical, thoracic (inside and outside the radiation fields) and lumbar spinal cord were measured. SUVmean of the thoracic spinal cord inside the radiation field was decreased significantly after radiotherapy compared to those before radiotherapy (p < 0.001). SUVmean of the cervical spinal cord showed the same trend but it was not statistically significant (p = 0.051). SUVmean of the thoracic spinal cord outside the radiation field and the lumbar spinal cord did not differ significantly before and after the radiotherapy (p = 0.146 and p = 0.701, respectively). The results suggest that glucose metabolism of the spinal cord is decreased in esophageal cancer patients after conventional dose radiotherapy.

The adaptation to pregnancy of spinal cord injured women.

PubMed

Craig, D I

1990-01-01

This study explored the experiences encountered by spinal cord injured women during pregnancy. The spinal cord injured women experienced complications associated with pregnancy: recurring urinary tract infections, an increase in incontinence, and autonomic dysreflexia. (The first two of these are not unique to spinal cord injury, but are common in all pregnancies.) They neither developed pressure areas nor experienced premature deliveries, major complications predicted by the literature. All felt they were victims of inadequate environmental design that hindered their mobility and inhibited their independence. Many of the psychosocial aspects studied proved to be common to pregnant women in general and not specific to the spinal cord injured population.

Skeletal muscle mitochondrial health and spinal cord injury.

PubMed

O'Brien, Laura C; Gorgey, Ashraf S

2016-10-18

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.

Modeling spinal cord biomechanics

NASA Astrophysics Data System (ADS)

Luna, Carlos; Shah, Sameer; Cohen, Avis; Aranda-Espinoza, Helim

2012-02-01

Regeneration after spinal cord injury is a serious health issue and there is no treatment for ailing patients. To understand regeneration of the spinal cord we used a system where regeneration occurs naturally, such as the lamprey. In this work, we analyzed the stress response of the spinal cord to tensile loading and obtained the mechanical properties of the cord both in vitro and in vivo. Physiological measurements showed that the spinal cord is pre-stressed to a strain of 10%, and during sinusoidal swimming, there is a local strain of 5% concentrated evenly at the mid-body and caudal sections. We found that the mechanical properties are homogeneous along the body and independent of the meninges. The mechanical behavior of the spinal cord can be characterized by a non-linear viscoelastic model, described by a modulus of 20 KPa for strains up to 15% and a modulus of 0.5 MPa for strains above 15%, in agreement with experimental data. However, this model does not offer a full understanding of the behavior of the spinal cord fibers. Using polymer physics we developed a model that relates the stress response as a function of the number of fibers.

NORADRENERGIC INNERVATION OF THE RAT SPINAL CORD CAUDAL TO A COMPLETE SPINAL CORD TRANSECTION: EFFECTS OF OLFACTORY ENSHEATHING GLIA

PubMed Central

Takeoka, Aya; Kubasak, Marc D.; Zhong, Hui; Kaplan, Jennifer; Roy, Roland R.; Phelps, Patricia E.

2010-01-01

Transplantation of olfactory bulb-derived olfactory ensheathing glia (OEG) combined with step training improves hindlimb locomotion in adult rats with a complete spinal cord transection. Spinal cord injury studies use the presence of noradrenergic (NA) axons caudal to the injury site as evidence of axonal regeneration and we previously found more NA axons just caudal to the transection in OEG- than media-injected spinal rats. We therefore hypothesized that OEG transplantation promotes descending coeruleospinal regeneration that contributes to the recovery of hindlimb locomotion. Now we report that NA axons are present throughout the caudal stump of both media- and OEG-injected spinal rats and they enter the spinal cord from the periphery via dorsal and ventral roots and along large penetrating blood vessels. These results indicate that the presence of NA fibers in the caudal spinal cord is not a reliable indicator of coeruleospinal regeneration. We then asked if NA axons appose cholinergic neurons associated with motor functions, i.e., central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more NA varicosities adjacent to central canal cluster cells, partition cells, and SMNs in the lumbar enlargement of OEG- than media-injected rats. As non-synaptic release of NA is common in the spinal cord, more associations between NA varicosities and motor-associated cholinergic neurons in the lumbar spinal cord may contribute to the improved treadmill stepping observed in OEG-injected spinal rats. This effect could be mediated through direct association with SMNs and/or indirectly via cholinergic interneurons. PMID:20025875

Acute lower motor neuron tetraparesis.

PubMed

Añor, Sònia

2014-11-01

Flaccid nonambulatory tetraparesis or tetraplegia is an infrequent neurologic presentation; it is characteristic of neuromuscular disease (lower motor neuron [LMN] disease) rather than spinal cord disease. Paresis beginning in the pelvic limbs and progressing to the thoracic limbs resulting in flaccid tetraparesis or tetraplegia within 24 to 72 hours is a common presentation of peripheral nerve or neuromuscular junction disease. Complete body flaccidity develops with severe decrease or complete loss of spinal reflexes in pelvic and thoracic limbs. Animals with acute generalized LMN tetraparesis commonly show severe motor dysfunction in all limbs and severe generalized weakness in all muscles. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2014-01-01

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

31st G. Heiner Sell Lectureship: Secondary Medical Consequences of Spinal Cord Injury

PubMed Central

Bauman, William A.; Korsten, Mark A.; Radulovic, Miroslav; Schilero, Gregory J.; Wecht, Jill M.; Spungen, Ann M.

2012-01-01

Persons with spinal cord injury (SCI) have secondary medical consequences of paralysis and/or the consequences of extreme inactivity. The metabolic changes that result from reduced activity include insulin resistance with carbohydrate disorders and dyslipidemia. A higher prevalence of coronary artery calcification was found in persons with SCI than that in matched able-bodied controls. A depression in anabolic hormones, circulating testosterone and growth hormone, has been described. Adverse soft tissue body composition changes of increased adiposity and reduced skeletal muscle are appreciated. Immobilization is the cause for sublesional disuse osteoporosis with an associated increased risk of fragility fracture. Bowel dysmotility affects all segments of the gastrointestinal tract, with an interest in better defining and addressing gastroesophageal reflux disease and difficulty with evacuation. Developing and testing more effective approaches to cleanse the bowel for elective colonoscopy are being evaluated. The extent of respiratory dysfunction depends on the level and completeness of SCI. Individuals with higher spinal lesions have both restrictive and obstructive airway disease. Pharmacological approaches and expiratory muscle training are being studied as interventions to improve pulmonary function and cough strength with the objective of reducing pulmonary complications. Persons with spinal lesions above the 6th thoracic level lack both cardiac and peripheral vascular mechanisms to maintain blood pressure, and they are frequently hypotensive, with even worse hypotension with upright posture. Persistent and/or orthostatic hypotension may predispose those with SCI to cognitive impairments. The safety and efficacy of anti-hypotensive agents to normalize blood pressure in persons with higher level cord lesions is being investigated. PMID:23459498

Spinal cord repair in MS

PubMed Central

Ciccarelli, O.; Altmann, D. R.; McLean, M. A.; Wheeler-Kingshott, C. A.; Wimpey, K.; Miller, D. H.; Thompson, A. J.

2010-01-01

Objective: To investigate the mechanisms of spinal cord repair and their relative contribution to clinical recovery in patients with multiple sclerosis (MS) after a cervical cord relapse, using spinal cord 1H-magnetic resonance spectroscopy (MRS) and volumetric imaging. Methods: Fourteen patients with MS and 13 controls underwent spinal cord imaging at baseline and at 1, 3, and 6 months. N-acetyl-aspartate (NAA) concentration, which reflects axonal count and metabolism in mitochondria, and the cord cross-sectional area, which indicates axonal count, were measured in the affected cervical region. Mixed effect linear regression models investigated the temporal evolution of these measures and their association with clinical changes. Ordinal logistic regressions identified predictors of recovery. Results: Patients who recovered showed a sustained increase in NAA after 1 month. In the whole patient group, a greater increase of NAA after 1 month was associated with greater recovery. Patients showed a significant decline in cord area during follow-up, which did not correlate with clinical changes. A worse recovery was predicted by a longer disease duration at study entry. Conclusions: The partial recovery of N-acetyl-aspartate levels after the acute event, which is concurrent with a decline in cord cross-sectional area, may be driven by increased axonal mitochondrial metabolism. This possible repair mechanism is associated with clinical recovery, and is less efficient in patients with longer disease duration. These insights into the mechanisms of spinal cord repair highlight the need to extend spinal cord magnetic resonance spectroscopy to other spinal cord disorders, and explore therapies that enhance recovery by modulating mitochondrial activity. GLOSSARY CI = confidence interval; EDSS = Expanded Disability Status Scale; FOV = field of view; MR = magnetic resonance; MRS = magnetic resonance spectroscopy; MS = multiple sclerosis; NAA = N-acetyl-aspartate; SC = spinal cord; TE = echo time; TI = inversion time; TR = repetition time. PMID:20107138

Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses

PubMed Central

Mishra, Asht M.; Pal, Ajay; Gupta, Disha

2017-01-01

Key points Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord.The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone.Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal.Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Abstract Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this protocol and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensorimotor function after injury to the central nervous system. PMID:28752624

Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses.

PubMed

Mishra, Asht M; Pal, Ajay; Gupta, Disha; Carmel, Jason B

2017-11-15

Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord. The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone. Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal. Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this protocol and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensorimotor function after injury to the central nervous system. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

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

PubMed

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

2017-03-15

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

Brain stem origins of spinal projections in the lizard Tupinambis nigropunctatus.

PubMed

Cruce, W L; Newman, D B

1981-05-10

In order to study brainstem origins of spinal projections, ten Tegu lizards (Tupinambis nigropunctatus) received complete or partial hemisections of the spinal cord at the first or second cervical segment. Their brains were processed for conventional Nissl staining. The sections were surveyed for the presence or absence of retrograde chromatolysis. Based on analysis and comparison of results from lesions in the various spinal cord funiculi, the following conclusions were reached: The interstitial nucleus projects ipsilaterally to the spinal cord via the medial longitudinal fasciculus, as does the middle reticular field of the metencephalon. The red nucleus and dorsal vagal motor nucleus both project contralaterally to the spinal cord via the dorsal part of the lateral funiculus. The superior reticular field in the rostral metencephalon and the ventrolateral vestibular nucleus project ipsilaterally to the spinal cord via the ventral funiculus. The dorsolateral metencephalic nucleus and the ventral part of the inferior reticular nucleus of the myelencephalon both project ipsilaterally to the spinal cord via the dorsal part of the lateral funiculus. Several brainstem nuclei in Tupinambis project bilaterally to the spinal cord. The ventrolateral metencephalic nucleus, for example, projects ipsilaterally to the cord via the medial longitudinal fasciculus and contralaterally via the dorsal part of the lateral funiculus. The dorsal part of the inferior reticular nucleus projects bilaterally to the spinal cord via the dorsal part of the lateral funiculus. The nucleus solitarius complex projects contralaterally via the dorsal part of the lateral funiculus but ipsilaterally via the middle of the lateral funiculus. The inferior raphe nucleus projects bilaterally to the spinal cord via the middle part of the lateral funiculus. These data suggest that supraspinal projections in reptiles, especially reticulospinal systems, are more highly differentiated than previously thought. On the other hand, recent findings in cat, opossum, and monkey reveal that the organization of supraspinal pathways in the Tegu lizard bears a striking resemblance to that observed in mammals.

Spinal cord aspergillus invasion--complication of an aspergilloma.

PubMed

Sheth, N K; Varkey, B; Wagner, D K

1985-12-01

Acute paraplegia developed in a 53-year-old man with pulmonary aspergilloma because of contiguous extension of Aspergillus infection to the epidural and subdural spaces and spinal cord. Histopathologic findings of the spinal cord showed Aspergillus hyphae penetrating the myelin sheath and myelomalacia, predominantly in the anterior and lateral columns. To the authors' knowledge, there have been no previous descriptions or illustrations of spinal cord involvement and the pathologic changes caused by Aspergillus infection.

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

DTIC Science & Technology

2014-10-01

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

Discrimination of heterogenous mRNAs encoding strychnine-sensitive glycine receptors in Xenopus oocytes by antisense oligonucleotides.

PubMed Central

Akagi, H; Patton, D E; Miledi, R

1989-01-01

Three synthetic oligodeoxynucleotides complementary to different parts of an RNA encoding a glycine receptor subunit were used to discriminate heterogenous mRNAs coding for glycine receptors in adult and neonatal rat spinal cord. Injection of the three antisense oligonucleotides into Xenopus oocytes specifically inhibited the expression of glycine receptors by adult spinal cord mRNA. In contrast, the antisense oligonucleotides were much less potent in inhibiting the expression of glycine receptors encoded by neonatal spinal cord mRNA. Northern blot analysis revealed that the oligonucleotides hybridized mostly to an adult cord transcript of approximately 10 kilobases in size. This band was also present in neonatal spinal cord mRNA but its density was about one-fourth of the adult cord message. There was no intense band in the low molecular weight position (approximately 2 kilobases), the existence of which was expected from electrophysiological studies with size-fractionated mRNA of neonatal spinal cord. Our results suggest that in the rat spinal cord there are at least three different types of mRNAs encoding functional strychnine-sensitive glycine receptors. Images PMID:2479016

Systemic hypothermia for the treatment of acute cervical spinal cord injury in sports.

PubMed

Dietrich, William Dalton; Cappuccino, Andrew; Cappuccino, Helen

2011-01-01

Spinal cord injury is a devastating condition that affects approximately 12,000 patients each year in the United States. Major causes for spinal cord injury include motor vehicle accidents, sports-related injuries, and direct trauma. Moderate hypothermia has gained attention as a potential therapy due to recent experimental and clinical studies and the use of modest systemic hypothermia (MSH) in high profile case of spinal cord injury in a National Football League (NFL) player. In experimental models of spinal cord injury, moderate hypothermia has been shown to improve functional recovery and reduce overall structural damage. In a recent Phase I clinical trial, systemic hypothermia has been shown to be safe and provide some encouraging results in terms of functional recovery. This review will summarize recent preclinical data, as well as clinical findings that support the continued investigations for the use of hypothermia in severe cervical spinal cord injury.

Spinal Cord Ischemia Secondary to Hypovolemic Shock

PubMed Central

Kapoor, Siddhant; Koh, Roy KM; Yang, Eugene WR; Hee, Hwan-Tak

2014-01-01

A 44-year-old male presented with symptoms of spinal cord compression secondary to metastatic prostate cancer. An urgent decompression at the cervical-thoracic region was performed, and there were no complications intraoperatively. Three hours postoperatively, the patient developed acute bilateral lower-limb paralysis (motor grade 0). Clinically, he was in class 3 hypovolemic shock. An urgent magnetic resonance imaging (MRI) was performed, showing no epidural hematoma. He was managed aggressively with medical therapy to improve his spinal cord perfusion. The patient improved significantly, and after one week, he was able to regain most of his motor functions. Although not commonly reported, spinal cord ischemia post-surgery should be recognized early, especially in the presence of hypovolemic shock. MRI should be performed to exclude other potential causes of compression. Spinal cord ischemia needs to be managed aggressively with medical treatment to improve spinal cord perfusion. The prognosis depends on the severity of deficits, and is usually favorable. PMID:25558328

Revisiting the segmental organization of the human spinal cord.

PubMed

Leijnse, J N; D'Herde, K

2016-09-01

In classic anatomic atlases, the spinal cord is standardly represented in its anatomical form with symmetrically emerging anterior and posterior roots, which at the level of the intervertebral foramen combine into the spinal nerves. The parts of the cord delimited by the boundaries of the roots are called segments or myelomeres. Associated with their regular repetitive appearance is the notion that the cord is segmentally organized. This segmental view is reinforced by clinical practice. Spinal cord roots innervate specific body parts. The level of cord trauma is diagnosed by the de-innervation symptoms of these parts. However, systemically, the case for a segmentally organized cord is not so clear. To date, developmental and genetic research points to a regionally rather than a segmentally organized cord. In the present study, to what degree the fila radicularia are segmentally implanted along the cord was investigated. The research hypothesis was that if the fila radicularia were non-segmentally implanted at the cord surface, it would be unlikely that the internal neuron stratum would be segmented. The visual segmented aspect of the myelomeres would then be the consequence of the necessary bundling of axons towards the vertebral foramen as the only exits of the vertebral canal, rather than of an underlying segment organization of the cord itself. To investigate the research hypothesis, the fila radicularia in the cervical-upper thoracic part of five spinal cords were detached from their spinal nerves and dissected in detail. The principal research question was if the fila radicularia are separated from their spinal nerves and dissected from their connective tissues up to the cord, would it be possible to reconstruct the original spinal segments from the morphology and interspaces of the fila? The dissections revealed that the anterior fila radicularia emerge from the cord at regular regionally modulated interspaces without systematic segmental delineations. The posterior fila radicularia are somewhat more segmentally implanted, but the pattern is individually inconsistent. The posterior and anterior roots have notable morphological differences, and hypotheses are presented to help explain these. The macroscopic observations are consistent with a regionally but not a segmentally organized cord. This conclusion was visually summarized in photographs of spinal cords with ipsilateral intact roots and contralateral individually dissected fila radicularia. It was suggested that this dual view of the spinal cord be added to the standard anatomic textbooks to counterbalance the current possibly biased view of a segmented cord. © 2016 Anatomical Society.

MRI Atlas-Based Measurement of Spinal Cord Injury Predicts Outcome in Acute Flaccid Myelitis.

PubMed

McCoy, D B; Talbott, J F; Wilson, Michael; Mamlouk, M D; Cohen-Adad, J; Wilson, Mark; Narvid, J

2017-02-01

Recent advances in spinal cord imaging analysis have led to the development of a robust anatomic template and atlas incorporated into an open-source platform referred to as the Spinal Cord Toolbox. Using the Spinal Cord Toolbox, we sought to correlate measures of GM, WM, and cross-sectional area pathology on T2 MR imaging with motor disability in patients with acute flaccid myelitis. Spinal cord imaging for 9 patients with acute flaccid myelitis was analyzed by using the Spinal Cord Toolbox. A semiautomated pipeline using the Spinal Cord Toolbox measured lesion involvement in GM, WM, and total spinal cord cross-sectional area. Proportions of GM, WM, and cross-sectional area affected by T2 hyperintensity were calculated across 3 ROIs: 1) center axial section of lesion; 2) full lesion segment; and 3) full cord atlas volume. Spearman rank order correlation was calculated to compare MR metrics with clinical measures of disability. Proportion of GM metrics at the center axial section significantly correlated with measures of motor impairment upon admission ( r [9] = -0.78; P = .014) and at 3-month follow-up ( r [9] = -0.66; P = .05). Further, proportion of GM extracted across the full lesion segment significantly correlated with initial motor impairment ( r [9] = -0.74, P = .024). No significant correlation was found for proportion of WM or proportion of cross-sectional area with clinical disability. Atlas-based measures of proportion of GM T2 signal abnormality measured on a single axial MR imaging section and across the full lesion segment correlate with motor impairment and outcome in patients with acute flaccid myelitis. This is the first atlas-based study to correlate clinical outcomes with segmented measures of T2 signal abnormality in the spinal cord. © 2017 by American Journal of Neuroradiology.

Dynamic Detection of Spinal Cord Position During Postural Changes Using Near-Infrared Reflectometry.

PubMed

Wolf, Erich W

2015-08-01

Motion of the spinal cord relative to a spinal cord stimulator epidural electrode array can cause suboptimal stimulation: either noxious, inefficient, or insufficient. Adaptive stimulation attempts to mitigate these effects by modulating stimulation parameters in a position-dependent fashion. Near-infrared (NIR) reflectometry is demonstrated to provide real-time direct measurement of spinal cord position at the site of stimulation, which can facilitate closed-loop adaptive stimulation during static and dynamic motion states. A miniature sensor array consisting of an NIR light emitting diode flanked by phototransistors potted in epoxy was placed in the dorsal epidural space of a human cadaver at the T8 level via laminotomy. Turgor of the subarachnoid space was maintained by intrathecal infusion of saline. NIR reflectance was measured as the cadaver was rotated about its longitudinal axis on a gantry. NIR reflectance was correlated with gantry position and velocity. NIR reflectometry suggests gravitational force is the primary determinant of cord position in static, ordinal positions. Under dynamic motion conditions, there was statistically significant cross-correlation between reflectometry data and the tangential velocity squared, suggesting that centripetal force was the primary determinant of cord position as the gantry was rotated. Reflectometry data strongly correlated with a simple geometric model of anticipated spinal cord precession within the spinal canal. Spinal cord position during dynamic motion has been shown to differ from static predictions due to additional influences such as centripetal force. These findings underscore limitations in extrapolating spinal cord position from surrogates such as body position or body acceleration at sites remote from the stimulating electrodes. NIR reflectometry offers a real-time direct measure of spinal cord position in both static and dynamic motion states, which may facilitate closed-loop adaptive stimulation applications. © 2015 International Neuromodulation Society.

Secondary damage in the spinal cord after motor cortex injury in rats.

PubMed

Weishaupt, Nina; Silasi, Gergely; Colbourne, Frederick; Fouad, Karim

2010-08-01

When neurons within the motor cortex are fatally injured, their axons, many of which project into the spinal cord, undergo wallerian degeneration. Pathological processes occurring downstream of the cortical damage have not been extensively studied. We created a focal forelimb motor cortex injury in rats and found that axons from cell bodies located in the hindlimb motor cortex (spared by the cortical injury) become secondarily damaged in the spinal cord. To assess axonal degeneration in the spinal cord, we quantified silver staining in the corticospinal tract (CST) at 1 week and 4 weeks after the injury. We found a significant increase in silver deposition at the thoracic spinal cord level at 4 weeks compared to 1 week post-injury. At both time points, no degenerating neurons could be found in the hindlimb motor cortex. In a separate experiment, we showed that direct injury of neurons within the hindlimb motor cortex caused marked silver deposition in the thoracic CST at 1 week post-injury, and declined thereafter. Therefore, delayed axonal degeneration in the thoracic spinal cord after a focal forelimb motor cortex injury is indicative of secondary damage at the spinal cord level. Furthermore, immunolabeling of spinal cord sections showed that a local inflammatory response dominated by partially activated Iba-1-positive microglia is mounted in the CST, a viable mechanism to cause the observed secondary degeneration of fibers. In conclusion, we demonstrate that following motor cortex injury, wallerian degeneration of axons in the spinal cord leads to secondary damage, which is likely mediated by inflammatory processes.

Spontaneous recovery of locomotion induced by remaining fibers after spinal cord transection in adult rats.

PubMed

You, Si-Wei; Chen, Bing-Yao; Liu, Hui-Ling; Lang, Bing; Xia, Jie-Lai; Jiao, Xi-Ying; Ju, Gong

2003-01-01

A major issue in analysis of experimental results after spinal cord injury is spontaneous functional recovery induced by remaining nerve fibers. The authors investigated the relationship between the degree of locomotor recovery and the percentage and location of the fibers that spared spinal cord transection. The spinal cords of 12 adult rats were transected at T9 with a razor blade, which often resulted in sparing of nerve fibers in the ventral spinal cord. The incompletely-transected animals were used to study the degree of spontaneous recovery of hindlimb locomotion, evaluated with the BBB rating scale, in correlation to the extent and location of the remaining fibers. Incomplete transection was found in the ventral spinal cord in 42% of the animals. The degree of locomotor recovery was highly correlated with the percentage of the remaining fibers in the ventral and ventrolateral funiculi. In one of the rats, 4.82% of remaining fibers in unilateral ventrolateral funiculus were able to sustain a certain recovery of locomotion. Less than 5% of remaining ventrolateral white matter is sufficient for an unequivocal motor recovery after incomplete spinal cord injury. Therefore, for studies with spinal cord transection, the completeness of sectioning should be carefully checked before any conclusion can be reached. The fact that the degree of locomotor recovery is correlated with the percentage of remaining fibers in the ventrolateral spinal cord, exclusive of most of the descending motor tracts, may imply an essential role of propriospinal connections in the initiation of spontaneous locomotor recovery.

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

PubMed

Béal, J L; Lopin, M C; Binnert, M

1993-01-01

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

Chronic spinal cord injury in the cervical spine of a young soccer player.

PubMed

Kato, Yoshihiko; Koga, Michiaki; Taguchi, Toshihiko

2010-05-12

A 17-year-old male soccer player presented with numbness in the upper- and lower-left extremities of 6 months' duration. He had no apparent history of trauma but experienced neck pain during heading of the ball 5 years prior. A high-signal intensity area was seen on T2-weighted magnetic resonance imaging (MRI) of the cervical spine. No muscle weakness was observed. Hypoesthesia was observed in bilateral forearms, hands, and extremities below the inguinal region. Plain radiographs in the neutral position showed local kyphosis at C3/4. A small protrusion of the C3/4 disk was observed on T1-weighted MRI. A high-signal area in the spinal cord at the C3/4 level was observed on T2-weighted MRI, but this was not enhanced by gadolinium. Multiple sclerosis, intramedullary spinal cord tumor, sarcoidosis and malignant lymphoma, and spinal cord injury were all considered in the differential diagnosis. However, in view of the clinical, laboratory, and radiological investigations, we concluded that repeated impacts to the neck caused by heading of the ball during soccer induced a chronic, minor spinal cord injury. This contributed to the high-signal intensity change of the spinal cord in T2-weighted MRI. The present case demonstrates that repeated impact may cause chronic spinal cord injury. Soccer, American football, or rugby players presenting with neck or extremity symptoms should not be overlooked for the possibility of latent spinal cord injury, as this could present later development of more severe or unrecoverable spinal cord injuries. Copyright 2010, SLACK Incorporated.

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

PubMed

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

2015-11-01

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

The Neuroprotective Effect of Kefir on Spinal Cord Ischemia/Reperfusion Injury in Rats.

PubMed

Guven, Mustafa; Akman, Tarik; Yener, Ali Umit; Sehitoglu, Muserref Hilal; Yuksel, Yasemin; Cosar, Murat

2015-05-01

The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (p<0.05). Catalase and superoxide dismutase levels of the kefir group were significantly higher than ischemia group (p<0.05). In histopathological samples, the kefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (p<0.05). In immunohistochemical staining, hipoxia-inducible factor-1α and caspase 3 immunopositive neurons were significantly decreased in kefir group compared with ischemia group (p<0.05). The neurological deficit scores of kefir group were significantly higher than ischemia group at 24 h (p<0.05). Our study revealed that kefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.

Ethyl pyruvate attenuates spinal cord ischemic injury with a wide therapeutic window through inhibiting high-mobility group box 1 release in rabbits.

PubMed

Wang, Qiang; Ding, Qian; Zhou, Yiming; Gou, Xingchun; Hou, Lichao; Chen, Shaoyang; Zhu, Zhenghua; Xiong, Lize

2009-06-01

Ethyl pyruvate (EP) has been reported to offer a protective effect against ischemic injury through its antiinflammatory action. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from ischemic cells. This study was designed to investigate the neuroprotective effect of EP against spinal cord ischemic injury and the potential role of HMGB1 in this process. EP was administered at various time points before or after 20 min of spinal cord ischemia in male New Zealand rabbits. All animals were sacrificed at 72 h after reperfusion with modified Tarlov criteria, and the spinal cord segment (L4) was harvested for histopathological examination and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining. The HMGB1 levels in serum and spinal cord tissue were analyzed by enzyme-linked immunosorbent assay. The treatment of EP at 30 min before ischemia or at 6 h after reperfusion significantly improved the hind-limb motor function scores and increased the numbers of normal motor neurons, which was accompanied with reduction of the number of apoptotic neurons and levels of HMGB1 in serum and spinal cord tissue. The HMGB1 contents of spinal cord tissue correlated well with the numbers of apoptotic motor neurons in the anterior spinal cord at 72 h after reperfusion. These results suggest that EP affords a strong protection against the transient spinal cord ischemic injury with a wide therapeutic window through inhibition of HMGB1 release.

Characterizing the Severity of Autonomic Cardiovascular Dysfunction after Spinal Cord Injury Using a Novel 24 Hour Ambulatory Blood Pressure Analysis Software.

PubMed

Popok, David W; West, Christopher R; Hubli, Michele; Currie, Katharine D; Krassioukov, Andrei V

2017-02-01

Cardiovascular disease is one of the leading causes of morbidity and mortality in the spinal cord injury (SCI) population. SCI may disrupt autonomic cardiovascular homeostasis, which can lead to persistent hypotension, irregular diurnal rhythmicity, and the development of autonomic dysreflexia (AD). There is currently no software available to perform automated detection and evaluation of cardiovascular autonomic dysfunction(s) such as those generated from 24 h ambulatory blood pressure monitoring (ABPM) recordings in the clinical setting. The objective of this study is to compare the efficacy of a novel 24 h ABPM Autonomic Dysfunction Detection Software against manual detection and to use the software to demonstrate the relationships between level of injury and the degree of autonomic cardiovascular impairment in a large cohort of individuals with SCI. A total of 46 individuals with cervical (group 1, n = 37) or high thoracic (group 2, n = 9) SCI participated in the study. Outcome measures included the frequency and severity of AD, frequency of hypotensive events, and diurnal variations in blood pressure and heart rate. There was good agreement between the software and manual detection of AD events (Bland-Altman limits of agreement = ±1.458 events). Cervical SCI presented with more frequent (p = 0.0043) and severe AD (p = 0.0343) than did high thoracic SCI. Cervical SCI exhibited higher systolic and diastolic blood pressure during the night and lower heart rate during the day than high thoracic SCI. In conclusion, our ABPM AD Detection Software was equally as effective in detecting the frequency and severity of AD and hypotensive events as manual detection, suggesting that this software can be used in the clinical setting to expedite ABPM analyses.

[Neuro-urological diagnosis and therapy of lower urinary tract dysfunction in patients with spinal cord injury : S2k Guideline of the German-Speaking Medical Society of Paraplegia (DMGP), AWMF register no. 179/001].

PubMed

Böthig, R; Domurath, B; Kaufmann, A; Bremer, J; Vance, W; Kurze, I

2017-06-01

Most patients with spinal cord injury (SCI) suffer from neurogenic lower urinary tract dysfunction (NLUTD), bowel dysfunction and sexual dysfunction. If these remain untreated, severe medical complications and serious limitations (restrictions) in quality of life are imminent. In the long term, there are considerable differences in the treatment results of highly specialized centers versus other treatment facilities. Against this background, a consensus-based guideline, according to the AWMF (Association of the Scientific Medical Societies in Germany) criteria (S2k), was developed by the neuro-urology working group of the DMPG (German-Speaking Medical Society of Paraplegia). The guideline defines the principles and objectives of the neuro-urological care of patients with SCI and discusses in detail the principles of diagnosis and therapy of NLUTD. The need for video-urodynamic studies as a basis for the classification of the NLUTD and as a foundation for the development of a treatment strategy is emphasized. Both conservative and surgical therapy options and their indications are explained in detail. Possible complications and their prevention in the long-term course of SCI are presented with a particular consideration of the specific features of urinary tract infections and autonomic dysreflexia. Finally, the principles of the provision of urological appliances are discussed. The presented S2k guideline provides the current standards in the neuro-urological care of patients with NLUTD due to SCI. Their consistent implementation both in the acute and chronic phase as well as in the context of lifelong surveillance of SCI patients should prevent the impending complications of NLUTD.

Neuroprotective effects of lycopene in spinal cord injury in rats via antioxidative and anti-apoptotic pathway.

PubMed

Hu, Wei; Wang, Hongbo; Liu, Zhenfeng; Liu, Yanlu; Wang, Rong; Luo, Xiao; Huang, Yifei

2017-03-06

Oxidative damage induced-mitochondrial dysfunction and apoptosis has been widely studied in spinal cord injury (SCI). Lycopene, a polyunsaturated hydrocarbon, has the highest antioxidant capacity compared to the other carotenoids. However, the role of lycopene in SCI is unknown. In the present study, we evaluated the antioxidant effects of lycopene on mitochondrial dysfunction and apoptosis following T10 contusion SCI in rats. The rats were randomized into 5 groups: the sham group, the SCI group and the SCI pre-treated with lycopene (5, 10, or 20mg/kg) group. The SCI group showed increased malondialdehyde (MDA) content, decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) ability, which indicated that SCI could induce oxidative damage. What's more, the SCI group showed decreased mRNA expression of cytochrome b and mitochondrial transcription factor A (Tfam), and decreased mitochondrial membrane potential (ΔYm), which indicated that SCI could induce mitochondrial dysfunction. Besides, the SCI group showed decreased protein expression of bcl-2 and mitochondrial cytochrome C, increased protein expression of cytosolic cytochrome C, cleaved caspase-9, cleaved caspase-3 and bax, and increased TUNEL-positive cell numbers, which indicated that SCI could induce cell apoptosis. Fortunately, the lycopene treatment significantly ameliorated oxidative damage, mitochondrial dysfunction and cell apoptosis via the reversion of those parameters described above in the dose of lycopene of 10 and 20mg/kg. In addition, lycopene significantly ameliorated the hind limb motor disturbances in the SCI+lyco10 group and the SCI+lyco20 group compared with the SCI group. These results suggested that lycopene administration could improve total antioxidant status and might have neuroprotective effects on SCI. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats.

PubMed

Gad, Parag; Choe, Jaehoon; Nandra, Mandheerej Singh; Zhong, Hui; Roy, Roland R; Tai, Yu-Chong; Edgerton, V Reggie

2013-01-21

Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array. We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1-100 Hz and 1-10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats. In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia. Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles.

Metabolite profile of a mouse model of Charcot–Marie–Tooth type 2D neuropathy: implications for disease mechanisms and interventions

PubMed Central

Bais, Preeti; Beebe, Kirk; Morelli, Kathryn H.; Currie, Meagan E.; Norberg, Sara N.; Evsikov, Alexei V.; Miers, Kathy E.; Seburn, Kevin L.; Guergueltcheva, Velina; Kremensky, Ivo; Jordanova, Albena; Bult, Carol J.

2016-01-01

ABSTRACT Charcot–Marie–Tooth disease encompasses a genetically heterogeneous class of heritable polyneuropathies that result in axonal degeneration in the peripheral nervous system. Charcot–Marie–Tooth type 2D neuropathy (CMT2D) is caused by dominant mutations in glycyl tRNA synthetase (GARS). Mutations in the mouse Gars gene result in a genetically and phenotypically valid animal model of CMT2D. How mutations in GARS lead to peripheral neuropathy remains controversial. To identify putative disease mechanisms, we compared metabolites isolated from the spinal cord of Gars mutant mice and their littermate controls. A profile of altered metabolites that distinguish the affected and unaffected tissue was determined. Ascorbic acid was decreased fourfold in the spinal cord of CMT2D mice, but was not altered in serum. Carnitine and its derivatives were also significantly reduced in spinal cord tissue of mutant mice, whereas glycine was elevated. Dietary supplementation with acetyl-L-carnitine improved gross motor performance of CMT2D mice, but neither acetyl-L-carnitine nor glycine supplementation altered the parameters directly assessing neuropathy. Other metabolite changes suggestive of liver and kidney dysfunction in the CMT2D mice were validated using clinical blood chemistry. These effects were not secondary to the neuromuscular phenotype, as determined by comparison with another, genetically unrelated mouse strain with similar neuromuscular dysfunction. However, these changes do not seem to be causative or consistent metabolites of CMT2D, because they were not observed in a second mouse Gars allele or in serum samples from CMT2D patients. Therefore, the metabolite ‘fingerprint’ we have identified for CMT2D improves our understanding of cellular biochemical changes associated with GARS mutations, but identification of efficacious treatment strategies and elucidation of the disease mechanism will require additional studies. PMID:27288508

Pain outcomes after surgery in patients with intramedullary spinal cord cavernous malformations.

PubMed

Deutsch, Harel

2010-09-01

The objective of the study was to quantify the improvement in pain levels for patients who have undergone surgery for intramedullary spinal cord cavernous malformations (SCCMs). The author reviewed medical records of patients who underwent surgery for an intramedullary SCCM between 2003 and 2010. Numerical pain scores (range 0-10) were recorded preoperatively and at follow-up. The follow-up period exceeded 1 year. Neurological status and subjective outcomes were assessed. Each patient underwent follow-up MR imaging. Five patients were identified with SCCMs who underwent surgery: 4 with thoracic and 1 with cervical lesions. Patients had been conservatively managed for an average of 5 years prior to surgery, and none had a history of acute hemorrhage or neurological deterioration during the observation period. The primary indication for surgery in each patient was pain, although 4 of 5 patients had some evidence of myelopathy on examination. Pain improved from a mean preoperative score of 8.6 to mean score of 2.0 (p < 0.01) at 1 month. Pain scores then increased to 3.7 (p < 0.01) at 1 year. All patients had some improvement in pain. No new motor weakness was noted, but all patients had increased symptoms of posterior-column dysfunction and numbness after surgery. Spinal cord intramedullary cavernous malformations are increasingly being diagnosed early with patients presenting with mostly pain symptoms. Removal of the lesion is reliably associated with improvement in pain scores but often the pain improvement is transient. While long-term worsening of pain scores occurs, at 1-year follow-up, patients reported pain scores were improved over preoperative scores. In all patients some degree of postoperative posterior-column dysfunction was present. Some of the immediate pain relief may be due to analgesia related to the myelotomy of newly described posterior column pain pathways. In patients with severe pain, surgery to remove SCCMs reduced the overall pain level at 1 year.

Spinal cord tumors: new views and future directions.

PubMed

Mechtler, Laszlo L; Nandigam, Kaveer

2013-02-01

Spinal cord tumors are uncommon neoplasms that, without treatment, can cause significant neurologic morbidity and mortality. The historic classification of spine tumors is based on the use of myelography with 3 main groups: (1) extramedullary extradural, (2) intradural extramedullary, and (3) intradural intramedullary. This chapter focuses on intramedullary spinal cord tumors (ISCTs), with an emphasis on new diagnostic imaging modalities and treatment options. The common ISCTs include ependymoma, astrocytoma and hemangioblastoma, which together account for over 90% of primary ISCTs. Rare tumors such as gangliglioma, oligodendroglioma, paraganglioma, melanocytoma, lipoma, and primary spinal cord lymphoma are also included in this review, in addition to spinal cord metastatic disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH2 induces penile erection via brain and spinal melanocortin receptors.

PubMed

Wessells, H; Hruby, V J; Hackett, J; Han, G; Balse-Srinivasan, P; Vanderah, T W

2003-01-01

Penile erection induced by alpha-melanocyte-stimulating hormone and melanocortin receptors (MC-R) in areas of the spinal cord and periphery has not been demonstrated. To elucidate sites of the proerectile action of melanocortin peptides, in awake male rats we administered the MC-R agonist Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH(2) (MT-II) i.c.v., intrathecal (i.th.) and i.v. and scored penile erection and yawning. Injection of the MC-R antagonist Ac-Nle-c[Asp-His-DNal(2')-Arg-Trp-Lys]-NH(2) (SHU-9119) i.c.v. or i.th. in combination with i.th. MT-II differentiated spinal from supraspinal effects. To exclude a site of action in the penis, we recorded intracavernous pressure responses to intracavernosal injection of MT-II in the anesthetized rat.I.c.v., i.th., and i.v. MT-II induced penile erections in a dose-dependent fashion. Yawning was observed with i.c.v. and i.v. MT-II, while spinal injection did not produce this behavior. Intrathecal delivery of MT-II to the lumbosacral spinal cord was more efficacious in inducing erections than i.c.v. or i.v. administration; SHU-9119 blocked the erectile responses to i.th. MT-II when injected i.th. but not i.c.v. Intracavernosal MT-II neither increased intracavernous pressure nor augmented neurostimulated erectile responses. We confirmed the central proerectile activity of MT-II and demonstrated that in addition to a site of action in the brain, the distal spinal cord contains melanocortin receptors that can initiate penile erection independent of higher centers. These results provide new insight into the central melanocortinergic pathways that mediate penile erection and may allow for more efficacious melanotropin-based therapy for erectile dysfunction.

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury

PubMed Central

Hou, Shaoping; Carson, David M.; Wu, Di; Klaw, Michelle C.; Houlé, John D.; Tom, Veronica J.

2016-01-01

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. PMID:26655672

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury.

PubMed

Hou, Shaoping; Carson, David M; Wu, Di; Klaw, Michelle C; Houlé, John D; Tom, Veronica J

2016-11-01

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 D 2 -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. Published by Elsevier Inc.

The negotiated equilibrium model of spinal cord function.

PubMed

Wolpaw, Jonathan R

2018-04-16

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

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

DTIC Science & Technology

2015-10-01

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

Coupling between the spinal cord and cervical vertebral column under tensile loading.

PubMed

Kroeker, Shannon G; Ching, Randal P

2013-02-22

Current neck injury criteria are based on structural failure of the spinal (vertebral) column without consideration of injury to the spinal cord. Since one of the primary functions of the vertebral column is to protect the cord, it stands to reason that a more refined measure of neck injury threshold would be the onset of spinal cord injury (SCI). This study investigated the relationship between axial strains in the cervical vertebral column and the spinal cord using an in vitro primate model (n=10) under continuous tensile loading. Mean failure loads occurred at 1951.5±396N with failure strains in the vertebral column of 16±5% at the level of failure. Average tensile strains in the spinal cord at failure were 11±5% resulting in a mean coupling ratio of 0.54±0.17 between C1 and C7. The level of peak strain measured in the spinal cord did not always occur at the location of vertebral column failure. Spinal cord strains were less than spine strains and coupling ratios were not significantly different along the length of the spine. The largest coupling ratio was measured in the atlanto-occipital joint whereas the smallest coupling ratio occurred at the adjacent C1-C2 joint. Copyright © 2012 Elsevier Ltd. All rights reserved.

Noradrenergic innervation of the rat spinal cord caudal to a complete spinal cord transection: effects of olfactory ensheathing glia.

PubMed

Takeoka, Aya; Kubasak, Marc D; Zhong, Hui; Kaplan, Jennifer; Roy, Roland R; Phelps, Patricia E

2010-03-01

Transplantation of olfactory bulb-derived olfactory ensheathing glia (OEG) combined with step training improves hindlimb locomotion in adult rats with a complete spinal cord transection. Spinal cord injury studies use the presence of noradrenergic (NA) axons caudal to the injury site as evidence of axonal regeneration and we previously found more NA axons just caudal to the transection in OEG- than media-injected spinal rats. We therefore hypothesized that OEG transplantation promotes descending coeruleospinal regeneration that contributes to the recovery of hindlimb locomotion. Now we report that NA axons are present throughout the caudal stump of both media- and OEG-injected spinal rats and they enter the spinal cord from the periphery via dorsal and ventral roots and along large penetrating blood vessels. These results indicate that the presence of NA fibers in the caudal spinal cord is not a reliable indicator of coeruleospinal regeneration. We then asked if NA axons appose cholinergic neurons associated with motor functions, i.e., central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more NA varicosities adjacent to central canal cluster cells, partition cells, and SMNs in the lumbar enlargement of OEG- than media-injected rats. As non-synaptic release of NA is common in the spinal cord, more associations between NA varicosities and motor-associated cholinergic neurons in the lumbar spinal cord may contribute to the improved treadmill stepping observed in OEG-injected spinal rats. This effect could be mediated through direct association with SMNs and/or indirectly via cholinergic interneurons. Copyright 2009 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-10-01

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

Spinal cord injury below-level neuropathic pain relief with dorsal root entry zone microcoagulation performed caudal to level of complete spinal cord transection.

PubMed

Falci, Scott; Indeck, Charlotte; Barnkow, Dave

2018-06-01

OBJECTIVE Surgically created lesions of the spinal cord dorsal root entry zone (DREZ) to relieve central pain after spinal cord injury (SCI) have historically been performed at and cephalad to, but not below, the level of SCI. This study was initiated to investigate the validity of 3 proposed concepts regarding the DREZ in SCI central pain: 1) The spinal cord DREZ caudal to the level of SCI can be a primary generator of SCI below-level central pain. 2) Neuronal transmission from a DREZ that generates SCI below-level central pain to brain pain centers can be primarily through sympathetic nervous system (SNS) pathways. 3) Perceived SCI below-level central pain follows a unique somatotopic map of DREZ pain-generators. METHODS Three unique patients with both intractable SCI below-level central pain and complete spinal cord transection at the level of SCI were identified. All 3 patients had previously undergone surgical intervention to their spinal cords-only cephalad to the level of spinal cord transection-with either DREZ microcoagulation or cyst shunting, in failed attempts to relieve their SCI below-level central pain. Subsequent to these surgeries, DREZ lesioning of the spinal cord solely caudal to the level of complete spinal cord transection was performed using electrical intramedullary guidance. The follow-up period ranged from 1 1/2 to 11 years. RESULTS All 3 patients in this study had complete or near-complete relief of all below-level neuropathic pain. The analyzed electrical data confirmed and enhanced a previously proposed somatotopic map of SCI below-level DREZ pain generators. CONCLUSIONS The results of this study support the following hypotheses. 1) The spinal cord DREZ caudal to the level of SCI can be a primary generator of SCI below-level central pain. 2) Neuronal transmission from a DREZ that generates SCI below-level central pain to brain pain centers can be primarily through SNS pathways. 3) Perceived SCI below-level central pain follows a unique somatotopic map of DREZ pain generators.

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

PubMed

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

2018-05-01

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

Spinal Cord Injury Causes Chronic Liver Pathology in Rats

PubMed Central

Sauerbeck, Andrew D.; Laws, J. Lukas; Bandaru, Veera V.R.; Popovich, Phillip G.; Haughey, Norman J.

2015-01-01

Abstract Traumatic spinal cord injury (SCI) causes major disruption to peripheral organ innervation and regulation. Relatively little work has investigated these post-SCI systemic changes, however, despite considerable evidence that multiple organ system dysfunction contributes to chronic impairments in health. Because metabolic dysfunction is common after SCI and the liver is a pivotal site for metabolic homeostasis, we sought to determine if liver pathology occurs as a result of SCI in a rat spinal contusion model. Histologic evidence showed excess lipid accumulation in the liver for at least 21 days post-injury after cervical or midthoracic SCI. Lipidomic analysis revealed an acute increase in hepatic ceramides as well as chronically elevated lactosylceramide. Post-SCI hepatic changes also included increased proinflammatory gene expression, including interleukin (IL)-1α, IL-1β, chemokine ligand-2, and tumor necrosis factor-α mRNA. These were coincident with increased CD68+ macrophages in the liver through 21 days post-injury. Serum alanine transaminase, used clinically to detect liver damage, was significantly increased at 21 days post-injury, suggesting that early metabolic and inflammatory damage preceded overt liver pathology. Surprisingly, liver inflammation was even detected after lumbar SCI. Collectively, these results suggest that SCI produces chronic liver injury with symptoms strikingly similar to those of nonalcoholic steatohepatitis (fatty liver disease). These clinically significant hepatic changes after SCI are known to contribute to systemic inflammation, cardiovascular disease, and metabolic syndrome, all of which are more prevalent in persons with SCI. Targeting acute and prolonged hepatic pathology may improve recovery and reduce long-term complications after SCI. PMID:25036371

Early presymptomatic cholinergic dysfunction in a murine model of amyotrophic lateral sclerosis

PubMed Central

Casas, Caty; Herrando-Grabulosa, Mireia; Manzano, Raquel; Mancuso, Renzo; Osta, Rosario; Navarro, Xavier

2013-01-01

Sporadic and familiar amyotrophic lateral sclerosis (ALS) cases presented lower cholinergic activity than in healthy individuals in their still preserved spinal motoneurons (MNs) suggesting that cholinergic reduction might occur before MN death. To unravel how and when cholinergic function is compromised, we have analyzed the spatiotemporal expression of choline acetyltransferase (ChAT) from early presymptomatic stages of the SOD1G93A ALS mouse model by confocal immunohistochemistry. The analysis showed an early reduction in ChAT content in soma and presynaptic boutons apposed onto MNs (to 76%) as well as in cholinergic interneurons in the lumbar spinal cord of the 30-day-old SOD1G93A mice. Cholinergic synaptic stripping occurred simultaneously to the presence of abundant surrounding major histocompatibility complex II (MHC-II)-positive microglia and the accumulation of nuclear Tdp-43 and the appearance of mild oxidative stress within MNs. Besides, there was a loss of neuronal MHC-I expression, which is necessary for balanced synaptic stripping after axotomy. These events occurred before the selective raise of markers of denervation such as ATF3. By the same time, alterations in postsynaptic cholinergic-related structures were also revealed with a loss of the presence of sigma-1 receptor, a Ca2+ buffering chaperone in the postsynaptic cisternae. By 2 months of age, ChAT seemed to accumulate in the soma of MNs, and thus efferences toward Renshaw interneurons were drastically diminished. In conclusion, cholinergic dysfunction in the local circuitry of the spinal cord may be one of the earliest events in ALS etiopathogenesis. PMID:23531559

Cervical spondylotic myelopathy.

PubMed

Tracy, Jennifer A; Bartleson, J D

2010-05-01

Cervical spondylosis is part of the aging process and affects most people if they live long enough. Degenerative changes affecting the intervertebral disks, vertebrae, facet joints, and ligamentous structures encroach on the cervical spinal canal and damage the spinal cord, especially in patients with a congenitally small cervical canal. Cervical spondylotic myelopathy (CSM) is the most common cause of myelopathy in adults. The anatomy, pathophysiology, clinical presentation, differential diagnosis, diagnostic investigation, natural history, and treatment options for CSM are summarized. Patients present with signs and symptoms of cervical spinal cord dysfunction with or without cervical nerve root injury. The condition may or may not be accompanied by pain in the neck and/or upper limb. The differential diagnosis is broad. Imaging, typically with magnetic resonance imaging, is the most useful diagnostic tool. Electrophysiologic testing can help exclude alternative diagnoses. The effectiveness of conservative treatments is unproven. Surgical decompression improves neurologic function in some patients and prevents worsening in others, but is associated with risk. Neurologists should be familiar with this very common condition. Patients with mild signs and symptoms of CSM can be monitored. Surgical decompression from an anterior or posterior approach should be considered in patients with progressive and moderate to severe neurologic deficits.

Complete spinal cord injury and brain dissection protocol for subsequent wholemount in situ hybridization in larval sea lamprey.

PubMed

Barreiro-Iglesias, Antón; Zhang, Guixin; Selzer, Michael E; Shifman, Michael I

2014-10-14

After a complete spinal cord injury, sea lampreys at first are paralyzed below the level of transection. However, they recover locomotion after several weeks, and this is accompanied by short distance regeneration (a few mm) of propriospinal axons and spinal-projecting axons from the brainstem. Among the 36 large identifiable spinal-projecting neurons, some are good regenerators and others are bad regenerators. These neurons can most easily be identified in wholemount CNS preparations. In order to understand the neuron-intrinsic mechanisms that favor or inhibit axon regeneration after injury in the vertebrates CNS, we determine differences in gene expression between the good and bad regenerators, and how expression is influenced by spinal cord transection. This paper illustrates the techniques for housing larval and recently transformed adult sea lampreys in fresh water tanks, producing complete spinal cord transections under microscopic vision, and preparing brain and spinal cord wholemounts for in situ hybridization. Briefly, animals are kept at 16°C and anesthetized in 1% Benzocaine in lamprey Ringer. The spinal cord is transected with iridectomy scissors via a dorsal approach and the animal is allowed to recover in fresh water tanks at 23 °C. For in situ hybridization, animals are reanesthetized and the brain and cord removed via a dorsal approach.

Intrinsic Resting-State Functional Connectivity in the Human Spinal Cord at 3.0 T.

PubMed

San Emeterio Nateras, Oscar; Yu, Fang; Muir, Eric R; Bazan, Carlos; Franklin, Crystal G; Li, Wei; Li, Jinqi; Lancaster, Jack L; Duong, Timothy Q

2016-04-01

To apply resting-state functional magnetic resonance (MR) imaging to map functional connectivity of the human spinal cord. Studies were performed in nine self-declared healthy volunteers with informed consent and institutional review board approval. Resting-state functional MR imaging was performed to map functional connectivity of the human cervical spinal cord from C1 to C4 at 1 × 1 × 3-mm resolution with a 3.0-T clinical MR imaging unit. Independent component analysis (ICA) was performed to derive resting-state functional MR imaging z-score maps rendered on two-dimensional and three-dimensional images. Seed-based analysis was performed for cross validation with ICA networks by using Pearson correlation. Reproducibility analysis of resting-state functional MR imaging maps from four repeated trials in a single participant yielded a mean z score of 6 ± 1 (P < .0001). The centroid coordinates across the four trials deviated by 2 in-plane voxels ± 2 mm (standard deviation) and up to one adjacent image section ± 3 mm. ICA of group resting-state functional MR imaging data revealed prominent functional connectivity patterns within the spinal cord gray matter. There were statistically significant (z score > 3, P < .001) bilateral, unilateral, and intersegmental correlations in the ventral horns, dorsal horns, and central spinal cord gray matter. Three-dimensional surface rendering provided visualization of these components along the length of the spinal cord. Seed-based analysis showed that many ICA components exhibited strong and significant (P < .05) correlations, corroborating the ICA results. Resting-state functional MR imaging connectivity networks are qualitatively consistent with known neuroanatomic and functional structures in the spinal cord. Resting-state functional MR imaging of the human cervical spinal cord with a 3.0-T clinical MR imaging unit and standard MR imaging protocols and hardware reveals prominent functional connectivity patterns within the spinal cord gray matter, consistent with known functional and anatomic layouts of the spinal cord.

Spinal Cord as an Adjunct to Brain Magnetic Resonance Imaging in Defining “No Evidence of Disease Activity” in Multiple Sclerosis

PubMed Central

Tummala, Subhash; Singhal, Tarun; Oommen, Vinit V.; Kim, Gloria; Khalid, Fariha; Healy, Brian C.

2017-01-01

Background: Monitoring patients with multiple sclerosis (MS) for “no evidence of disease activity” (NEDA) may help guide disease-modifying therapy (DMT) management decisions. Whereas surveillance brain magnetic resonance imaging (MRI) is common, the role of spinal cord monitoring for NEDA is unknown. Objective: To evaluate the role of brain and spinal cord 3T MRI in the 1-year evaluation of NEDA. Methods: Of 61 study patients (3 clinically isolated syndrome, 56 relapsing-remitting, 2 secondary progressive), 56 (91.8%) were receiving DMT. The MRI included brain fluid-attenuated inversion recovery and cervical/thoracic T2-weighted fast spin echo images. On MRI, NEDA was defined as the absence of new or enlarging T2 lesions at 1 year. Results: Thirty-nine patients (63.9%) achieved NEDA by brain MRI, only one of whom had spinal cord activity. This translates to a false-positive rate for NEDA based on the brain of 2.6% (95% CI, 0.1%–13.5%). Thirty-eight patients (62.3%) had NEDA by brain and spinal cord MRI. Fifty-five patients (90.2%) had NEDA by spinal cord MRI, 17 of whom had brain activity. Of the 22 patients (36.1%) with brain changes, 5 had spinal cord changes. No evidence of disease activity was sustained in 48.3% of patients at 1 year and was the same with the addition of spinal cord MRI. Patients with MRI activity in either the brain or the spinal cord only were more likely to have activity in the brain (P = .0001). Conclusions: Spinal cord MRI had a low diagnostic yield as an adjunct to brain MRI at 3T in monitoring patients with MS for NEDA over 1 year. Studies with larger data sets are needed to confirm these findings. PMID:28603465

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

PubMed Central

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

2018-01-01

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

The distribution and origin of a novel brain peptide, neuropeptide Y, in the spinal cord of several mammals.

PubMed

Gibson, S J; Polak, J M; Allen, J M; Adrian, T E; Kelly, J S; Bloom, S R

1984-07-20

The distribution of neuropeptide Y [NPY]-immunoreactive material was examined in the spinal cord and dorsal root ganglia of rat, guinea-pig, cat, marmoset, and horse. Considerable concentrations of NPY and similar distribution patterns of immunoreactive nerve fibres were found in the spinal cord of all species investigated. The dorsal root ganglia of the cat and the horse contained numerous immunoreactive nerve fibres, but in these species, as in the other three studied [rat, guinea-pig, marmoset], no positively stained cell bodies were found. Neuropeptide Y-immunoreactive nerves were observed at all levels of the spinal cord, being most concentrated in the dorsal horn. In the rat, guinea-pig, and marmoset, there was a marked increase of NPY-immunoreactive fibres in the lumbosacral regions of the spinal cord, and this was reflected by a considerable increase of extractable NPY. Estimations of NPY-immunoreactive material in the various regions of the rat spinal cord were as follows: cervical, 13.8 +/- 1.0; thoracic, 21.1 +/- 2.5; lumbar, 16.3 +/- 2.9; sacral, 92.4 +/- 8.5 pmol/gm wet weight of tissue +/- SEM. In the ventral portion of the guinea-pig spinal cord they were as follows: cervical, 7.1 +/- 1.2; thoracic, 8.2 +/- 3.6; lumbar, 22.6 +/- 7.0; sacral, 36.7 +/- 9.5 pmol/gm wet weight of tissue +/- SEM. Analysis of spinal cord extracts by reverse phase high performance liquid chromatography [HPLC] demonstrated that NPY-immunoreactive material elutes in the position of pure NPY standard. No changes in the concentration and distribution of the NPY-like material in the rat spinal cord were observed following a variety of surgical and pharmacological manipulations, including cervical rhizotomy, sciatic nerve section and ligation, and local application of capsaicin [50 mM] to one sciatic nerve. It is therefore suggested that most of the NPY-immunoreactive material in the spinal cord is derived either from intrinsic nerve cell bodies or from supraspinal tracts.

Effects of wheelchair propulsion on neuropathic pain and resting electroencephalography after spinal cord injury.

PubMed

Sato, Gosuke; Osumi, Michihiro; Morioka, Shu

2017-01-31

To investigate the effects of wheelchair propulsion on neuropathic pain and to examine resting electroencephalography pre- and post-wheelchair propulsion after spinal cord injury. Cross-sectional study. Eleven individuals with spinal cord injury and pain and 10 healthy controls. Single-session 15-min wheelchair propulsion and measurement of resting electroence-phalography. Effects of wheelchair propulsion were investigated using numerical rating scale (NRS) for neuropathic pain and short-form Profile of Mood States-Brief for mood. Peak alpha frequency on electroencephalography was calculated in 4 regions of interest; frontal, central, parietal and occipital areas. These outcomes were compared between pre- and post-wheelchair propulsion. Ten participants with spinal cord injury and all healthy controls completed the wheelchair propulsion exercise. NRS scores and negative mood were significantly improved following the wheelchair propulsion exercise. Pre-wheelchair propulsion, parietal and occipital peak alpha frequencies were significantly lower in the spinal cord injury group compared with the healthy controls group. Post-wheelchair propulsion, central peak alpha frequency increased in the spinal cord injury group. Wheelchair propulsion exercise temporarily decreased neuropathic pain intensity, improved negative mood, and modified alpha activity in spinal cord injury.

Nestin- and Doublecortin-Positive Cells Reside in Adult Spinal Cord Meninges and Participate in Injury-Induced Parenchymal Reaction

PubMed Central

Decimo, Ilaria; Bifari, Francesco; Rodriguez, Francisco Javier; Malpeli, Giorgio; Dolci, Sissi; Lavarini, Valentina; Pretto, Silvia; Vasquez, Sandra; Sciancalepore, Marina; Montalbano, Alberto; Berton, Valeria; Krampera, Mauro; Fumagalli, Guido

2011-01-01

Adult spinal cord has little regenerative potential, thus limiting patient recovery following injury. In this study, we describe a new population of cells resident in the adult rat spinal cord meninges that express the neural stem/precursor markers nestin and doublecortin. Furthermore, from dissociated meningeal tissue a neural stem cell population was cultured in vitro and subsequently shown to differentiate into functional neurons or mature oligodendrocytes. Proliferation rate and number of nestin- and doublecortin-positive cells increased in vivo in meninges following spinal cord injury. By using a lentivirus-labeling approach, we show that meningeal cells, including nestin- and doublecortin-positive cells, migrate in the spinal cord parenchyma and contribute to the glial scar formation. Our data emphasize the multiple roles of meninges in the reaction of the parenchyma to trauma and indicate for the first time that spinal cord meninges are potential niches harboring stem/precursor cells that can be activated by injury. Meninges may be considered as a new source of adult stem/precursor cells to be further tested for use in regenerative medicine applied to neurological disorders, including repair from spinal cord injury. Stem Cells 2011;29:2062–2076. PMID:22038821

Nestin- and doublecortin-positive cells reside in adult spinal cord meninges and participate in injury-induced parenchymal reaction.

PubMed

Decimo, Ilaria; Bifari, Francesco; Rodriguez, Francisco Javier; Malpeli, Giorgio; Dolci, Sissi; Lavarini, Valentina; Pretto, Silvia; Vasquez, Sandra; Sciancalepore, Marina; Montalbano, Alberto; Berton, Valeria; Krampera, Mauro; Fumagalli, Guido

2011-12-01

Adult spinal cord has little regenerative potential, thus limiting patient recovery following injury. In this study, we describe a new population of cells resident in the adult rat spinal cord meninges that express the neural stem/precursor markers nestin and doublecortin. Furthermore, from dissociated meningeal tissue a neural stem cell population was cultured in vitro and subsequently shown to differentiate into functional neurons or mature oligodendrocytes. Proliferation rate and number of nestin- and doublecortin-positive cells increased in vivo in meninges following spinal cord injury. By using a lentivirus-labeling approach, we show that meningeal cells, including nestin- and doublecortin-positive cells, migrate in the spinal cord parenchyma and contribute to the glial scar formation. Our data emphasize the multiple roles of meninges in the reaction of the parenchyma to trauma and indicate for the first time that spinal cord meninges are potential niches harboring stem/precursor cells that can be activated by injury. Meninges may be considered as a new source of adult stem/precursor cells to be further tested for use in regenerative medicine applied to neurological disorders, including repair from spinal cord injury. Copyright © 2011 AlphaMed Press.

Variations in the formation of the human caudal spinal cord.

PubMed

Saraga-Babić, M; Sapunar, D; Wartiovaara, J

1995-01-01

Collection of 15 human embryos between 4-8 developmental weeks was used to histologically investigate variations in the development of the caudal part of the spinal cord and the neighboring axial organs (notochord and vertebral column). In the 4-week embryo, two types of neurulation were parallelly observed along the anteroposterior body axis: primary in the areas cranial to the neuroporus caudalis and secondary in the more caudal tail regions. In the 5-week embryos, both parts of the neural tube fused, forming only one continuous lumen in the developing spinal cord. In the three examined embryos we found anomalous pattern of spinal cord formation. Caudal parts of these spinal cords displayed division of their central canal into two or three separate lumina, each surrounded by neuroepithelial layer. In the caudal area of the spinal cord, derived by secondary neurulation, formation of separate lumina was neither connected to any anomalous notochord or vertebral column formation, nor the appearance of any major axial disturbances. We suggest that development of the caudal part of the spinal cord differs from its cranial region not only in the type of neurulation, but also in the destiny of its derivatives and possible modes of abnormality formation.

Central Pain Syndrome

MedlinePlus

... cord. This syndrome can be caused by stroke, multiple sclerosis, tumors, epilepsy, brain or spinal cord trauma, or ... cord. This syndrome can be caused by stroke, multiple sclerosis, tumors, epilepsy, brain or spinal cord trauma, or ...

Perspectives on the rapid eye movement sleep switch in rapid eye movement sleep behavior disorder.

PubMed

Ramaligam, Vetrivelan; Chen, Michael C; Saper, Clifford B; Lu, Jun

2013-08-01

Rapid eye movement (REM) sleep in mammals is associated with wakelike cortical and hippocampal activation and concurrent postural muscle atonia. Research during the past 5 decades has revealed the details of the neural circuitry regulating REM sleep and muscle atonia during this state. REM-active glutamatergic neurons in the sublaterodorsal nucleus (SLD) of the dorsal pons are critical for generation for REM sleep atonia. Descending projections from SLD glutamatergic neurons activate inhibitory premotor neurons in the ventromedial medulla (VMM) and in the spinal cord to antagonize the glutamatergic supraspinal inputs on the motor neurons during REM sleep. REM sleep behavior disorder (RBD) consists of simple behaviors (i.e., twitching, jerking) and complex behaviors (i.e., defensive behavior, talking). Animal research has lead to the hypothesis that complex behaviors in RBD are due to SLD pathology, while simple behaviors of RBD may be due to less severe SLD pathology or dysfunction of the VMM, ventral pons, or spinal cord. Copyright © 2013 Elsevier B.V. All rights reserved.

Significance of fixation of the vertebral column for spinal cord injury experiments.

PubMed

Liu, Fei; Luo, Zhuo-Jin; You, Si-Wei; Jiao, Xi-Ying; Meng, Xiao-Mei; Shi, Ming; Wang, Chun-Ting; Ju, Gong

2003-08-01

Thoracic spinal cord transections were performed in adult rats. The animals were divided into two groups, with or without internal fixation of the involved vertebral column. Histologic and immunohistochemical studies were performed to compare the effect of internal fixation of the vertebral column. To find out the aspects and extent of beneficial effects of vertebral column fixation for spinal cord repair. Vertebral column fixation is a routine procedure in clinical spinal cord surgery. Paradoxically, most, if not all, animal spinal cord experiments seem to have ignored the importance of vertebral column fixation. During trunk movements, the vertebral column flexes to different directions, accompanied by bending of the spinal cord. Following spinal cord lesions, with frequent bending of the cord there will be repeated bleeding, inflammation, and other pathologic processes at the lesion site. Thus, the healing process will be hampered. The severity of the damages that will be brought about by bending of the cord is, to a certain degree, unpredictable. There will be rather big individual variations in injury and repair among the same type of experiments, rendering quantification and conclusion difficult. Adult Sprague-Dawley rats were used. The thoracic spinal cord was transected. Strong stainless steel wires were used for internal fixation of the vertebral column. The histology of the horizontal sections of the spinal cord segment, which included the lesion site, was examined at the 14th postoperative day. The volumes of the secondary degeneration and meningeal scar, the gap between the borders of the proximal and distal stumps of the transected spinal cord, the thickness of the meningeal scar, the astrocytic reaction, and the abundance of regenerating nerve fibers at the lesion site were compared between the vertebral column fixed and nonfixed groups. Whenever possible, the results were evaluated quantitatively. In all these aspects, the internally fixed group was consistently far better than the unfixed group. The quantitative analyses were as follows (fixed/unfixed): 1)volume of secondary degeneration: 1.07 +/- 0.20/1.81 +/- 0.43 mm3 (P < 0.01); 2) volume of meningeal scar: 2.38 +/- 0.55/4.34 +/- 1.40 mm3 (P < 0.05); 3) distance between cord stumps: 1.38 +/- 0.34/2.35 +/- 0.79 mm (P < 0.05); 4) the mean thinnest dimension of the meningeal scar: 0.90 +/- 0.43/1.98 +/- 0.85 mm (P < 0.05). Vertebral column fixation is a crucial procedure for spinal cord animal experiments.

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

PubMed

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

2012-04-01

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

Novel aspects of spinal cord evoked potentials (SCEPs) in the evaluation of dorso-ventral and lateral mechanical impacts on the spinal cord.

PubMed

Rad, Iman; Kouhzaei, Sogolie; Mobasheri, Hamid; Saberi, Hooshang

2015-02-01

The aim of the current study was to mimic mechanical impacts on the spinal cord by manifesting the effects of dorsoventral (DVMP) and lateral (LMP) mechanical pressure on neural activity to address points to be considered during surgery for different purposes, including spinal cord decompression. Spinal cords of anesthetized rats were compressed at T13. Different characteristics of axons, including vulnerability, excitability, and conduction velocity (CV), in response to promptness, severity, and duration of pressure were assessed by spinal cord evoked potentials (SCEPs). Real-time SCEPs recorded at L4-5 revealed N1, N2, and N3 peaks that were used to represent the activity of injured sensory afferents, interneurons, and MN fibers. The averaged SCEP recordings were fitted by trust-region algorithm to find the equivalent Gaussian and polynomial equations. The pyramidal and extrapyramidal pathways possessed CVs of 3-11 and 16-80 m s(-1), respectively. DVMP decreased the excitability of myelinated neural fibers in antidromic and orthodromic pathways. The excitability of fibers in extrapyramidal and pyramidal pathways of lateral corticospinal (LCS) and anterior corticospinal (ACS) tracts decreased following LMP. A significant drop in the amplitude of N3 and its conduction velocity (CV) revealed higher susceptibility of less-myelinated fibers to both DVMP and LMP. The best parametric fitting model for triplet healthy spinal cord CAP was a six-term Gaussian equation (G6) that fell into a five-term equation (G5) at the complete compression stage. The spinal cord is more susceptible to dorsoventral than lateral mechanical pressures, and this should be considered in spinal cord operations. SCEPs have shown promising capabilities for evaluating the severity of SCI and thus can be applied for diagnostic or prognostic intraoperative monitoring (IOM).

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

PubMed

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

2018-05-01

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

Retained differentiation capacity of human skeletal muscle satellite cells from spinal cord-injured individuals.

PubMed

Savikj, Mladen; Ruby, Maxwell A; Kostovski, Emil; Iversen, Per O; Zierath, Juleen R; Krook, Anna; Widegren, Ulrika

2018-06-01

Despite the well-known role of satellite cells in skeletal muscle plasticity, the effect of spinal cord injury on their function in humans remains unknown. We determined whether spinal cord injury affects the intrinsic ability of satellite cells to differentiate and produce metabolically healthy myotubes. We obtained vastus lateralis biopsies from eight spinal cord-injured and six able-bodied individuals. Satellite cells were isolated, grown and differentiated in vitro. Gene expression was measured by quantitative PCR. Abundance of differentiation markers and regulatory proteins was determined by Western blotting. Protein synthesis and fatty acid oxidation were measured by radioactive tracer-based assays. Activated satellite cells (myoblasts) and differentiated myotubes derived from skeletal muscle of able-bodied and spinal cord-injured individuals expressed similar (P > 0.05) mRNA levels of myogenic regulatory factors. Myogenic differentiation factor 1 expression was higher in myoblasts from spinal cord-injured individuals. Desmin and myogenin protein content was increased upon differentiation in both groups, while myotubes from spinal cord-injured individuals contained more type I and II myosin heavy chain. Phosphorylated and total protein levels of Akt-mechanistic target of rapamycin and forkhead box protein O signalling axes and protein synthesis rate in myotubes were similar (P > 0.05) between groups. Additionally, fatty acid oxidation of myotubes from spinal cord-injured individuals was unchanged (P > 0.05) compared to able-bodied controls. Our results indicate that the intrinsic differentiation capacity of satellite cells and metabolic characteristics of myotubes are preserved following spinal cord injury. This may inform potential interventions targeting satellite cell activation to alleviate skeletal muscle atrophy. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

The Neuroprotective Effect of Kefir on Spinal Cord Ischemia/Reperfusion Injury in Rats

PubMed Central

Akman, Tarik; Yener, Ali Umit; Sehitoglu, Muserref Hilal; Yuksel, Yasemin; Cosar, Murat

2015-01-01

Objective The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. Methods Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. Results The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (p<0.05). Catalase and superoxide dismutase levels of the kefir group were significantly higher than ischemia group (p<0.05). In histopathological samples, the kefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (p<0.05). In immunohistochemical staining, hipoxia-inducible factor-1α and caspase 3 immunopositive neurons were significantly decreased in kefir group compared with ischemia group (p<0.05). The neurological deficit scores of kefir group were significantly higher than ischemia group at 24 h (p<0.05). Conclusion Our study revealed that kefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future. PMID:26113960

Effects of spinal cord stimulation in angina pectoris induced by pacing and possible mechanisms of action.

PubMed Central

Mannheimer, C; Eliasson, T; Andersson, B; Bergh, C H; Augustinsson, L E; Emanuelsson, H; Waagstein, F

1993-01-01

OBJECTIVE--To investigate the effects of spinal cord stimulation on myocardial ischaemia, coronary blood flow, and myocardial oxygen consumption in angina pectoris induced by atrial pacing. DESIGN--The heart was paced to angina during a control phase and treatment with spinal cord stimulation. Blood samples were drawn from a peripheral artery and the coronary sinus. SETTING--Multidisciplinary pain centre, department of medicine, Ostra Hospital, and Wallenberg Research Laboratory, Sahlgrenska Hospital, Gothenburg, Sweden. SUBJECTS--Twenty patients with intractable angina pectoris, all with a spinal cord stimulator implanted before the study. RESULTS--Spinal cord stimulation increased patients' tolerance to pacing (p < 0.001). At the pacing rate comparable to that producing angina during the control recording, myocardial lactate production during control session turned into extraction (p = 0.003) and, on the electrocardiogram, ST segment depression decreased, time to ST depression increased, and time to recovery from ST depression decreased (p = 0.01; p < 0.05, and p < 0.05, respectively). Spinal cord stimulation also reduced coronary sinus blood flow (p = 0.01) and myocardial oxygen consumption (p = 0.02). At the maximum pacing rate during treatment, all patients experienced anginal pain. Myocardial lactate extraction reverted to production (p < 0.01) and the magnitude and duration of ST segment depression increased to the same values as during control pacing, indicating that myocardial ischaemia during treatment with spinal cord stimulation gives rise to anginal pain. CONCLUSIONS--Spinal cord stimulation has an anti-anginal and anti-ischaemic effect in severe coronary artery disease. These effects seem to be secondary to a decrease in myocardial oxygen consumption. Furthermore, myocardial ischemia during treatment gives rise to anginal pain. Thus, spinal cord stimulation does not deprive the patient of a warning signal. PMID:8400930

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

PubMed

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

2017-09-01

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

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

PubMed

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

2013-06-07

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

Fast and accurate semi-automated segmentation method of spinal cord MR images at 3T applied to the construction of a cervical spinal cord template.

PubMed

El Mendili, Mohamed-Mounir; Chen, Raphaël; Tiret, Brice; Villard, Noémie; Trunet, Stéphanie; Pélégrini-Issac, Mélanie; Lehéricy, Stéphane; Pradat, Pierre-François; Benali, Habib

2015-01-01

To design a fast and accurate semi-automated segmentation method for spinal cord 3T MR images and to construct a template of the cervical spinal cord. A semi-automated double threshold-based method (DTbM) was proposed enabling both cross-sectional and volumetric measures from 3D T2-weighted turbo spin echo MR scans of the spinal cord at 3T. Eighty-two healthy subjects, 10 patients with amyotrophic lateral sclerosis, 10 with spinal muscular atrophy and 10 with spinal cord injuries were studied. DTbM was compared with active surface method (ASM), threshold-based method (TbM) and manual outlining (ground truth). Accuracy of segmentations was scored visually by a radiologist in cervical and thoracic cord regions. Accuracy was also quantified at the cervical and thoracic levels as well as at C2 vertebral level. To construct a cervical template from healthy subjects' images (n=59), a standardization pipeline was designed leading to well-centered straight spinal cord images and accurate probability tissue map. Visual scoring showed better performance for DTbM than for ASM. Mean Dice similarity coefficient (DSC) was 95.71% for DTbM and 90.78% for ASM at the cervical level and 94.27% for DTbM and 89.93% for ASM at the thoracic level. Finally, at C2 vertebral level, mean DSC was 97.98% for DTbM compared with 98.02% for TbM and 96.76% for ASM. DTbM showed similar accuracy compared with TbM, but with the advantage of limited manual interaction. A semi-automated segmentation method with limited manual intervention was introduced and validated on 3T images, enabling the construction of a cervical spinal cord template.

The Lesioned Spinal Cord Is a “New” Spinal Cord: Evidence from Functional Changes after Spinal Injury in Lamprey

PubMed Central

Parker, David

2017-01-01

Finding a treatment for spinal cord injury (SCI) focuses on reconnecting the spinal cord by promoting regeneration across the lesion site. However, while regeneration is necessary for recovery, on its own it may not be sufficient. This presumably reflects the requirement for regenerated inputs to interact appropriately with the spinal cord, making sub-lesion network properties an additional influence on recovery. This review summarizes work we have done in the lamprey, a model system for SCI research. We have compared locomotor behavior (swimming) and the properties of descending inputs, locomotor networks, and sensory inputs in unlesioned animals and animals that have received complete spinal cord lesions. In the majority (∼90%) of animals swimming parameters after lesioning recovered to match those in unlesioned animals. Synaptic inputs from individual regenerated axons also matched the properties in unlesioned animals, although this was associated with changes in release parameters. This suggests against any compensation at these synapses for the reduced descending drive that will occur given that regeneration is always incomplete. Compensation instead seems to occur through diverse changes in cellular and synaptic properties in locomotor networks and proprioceptive systems below, but also above, the lesion site. Recovery of locomotor performance is thus not simply the reconnection of the two sides of the spinal cord, but reflects a distributed and varied range of spinal cord changes. While locomotor network changes are insufficient on their own for recovery, they may facilitate locomotor outputs by compensating for the reduction in descending drive. Potentiated sensory feedback may in turn be a necessary adaptation that monitors and adjusts the output from the “new” locomotor network. Rather than a single aspect, changes in different components of the motor system and their interactions may be needed after SCI. If these are general features, and where comparisons with mammalian systems can be made effects seem to be conserved, improving functional recovery in higher vertebrates will require interventions that generate the optimal spinal cord conditions conducive to recovery. The analyses needed to identify these conditions are difficult in the mammalian spinal cord, but lower vertebrate systems should help to identify the principles of the optimal spinal cord response to injury. PMID:29163065

Low-Grade Inflammation and Spinal Cord Injury: Exercise as Therapy?

PubMed Central

da Silva Alves, Eduardo; de Aquino Lemos, Valdir; Ruiz da Silva, Francieli; Lira, Fabio Santos; dos Santos, Ronaldo Vagner Thomathieli; Rosa, João Paulo Pereira; Caperuto, Erico; Tufik, Sergio; de Mello, Marco Tulio

2013-01-01

An increase in the prevalence of obesity in people with spinal cord injury can contribute to low-grade chronic inflammation and increase the risk of infection in this population. A decrease in sympathetic activity contributes to immunosuppression due to the lower activation of immune cells in the blood. The effects of physical exercise on inflammatory parameters in individuals with spinal cord injury have not been well described. We conducted a review of the literature published from 1974 to 2012. This review explored the relationships between low-grade inflammation, spinal cord injury, and exercise to discuss a novel mechanism that might explain the beneficial effects of exercise involving an increase in catecholamines and cytokines in people with spinal cord injury. PMID:23533315

Transplantation of neurotrophin-3-transfected bone marrow mesenchymal stem cells for the repair of spinal cord injury.

PubMed

Dong, Yuzhen; Yang, Libin; Yang, Lin; Zhao, Hongxing; Zhang, Chao; Wu, Dapeng

2014-08-15

Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury.

Transverse myelitis-like presentation of methanol intoxication: A case report and review of the literature.

PubMed

Algahtani, Hussein; Shirah, Bader; Ahmad, Raafat; Abobaker, Hind; Hmoud, Mohammed

2018-01-01

Methanol is the simplest member of alcohol family. However, it is an extremely toxic substance to humans upon exposure with severe and detrimental effects that range from visual loss to death. Spinal cord involvement in methanol intoxication is a rare occurrence. In this article, we are reporting a case of methanol intoxication with extensive spinal cord involvement possibly due to necrosis. A literature review yielded only two cases of spinal cord involvement due to methanol intoxication. Our article is the first to discuss the spinal cord involvement specifically including interesting neuroimaging features. We recommend performing MRI of the cervicothoracic spine in every methanol intoxication case to exclude both asymptomatic and symptomatic cases of spinal cord involvement.

Differences in Affect, Life Satisfaction, and Depression between Successfully and Unsuccessfully Rehabilitated Persons with Spinal Cord Injuries

ERIC Educational Resources Information Center

Chapin, Martha H.; Holbert, Donald

2009-01-01

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…

Intramedullary spinal metastasis of a carcinoid tumor.

PubMed

Kumar, Jay I; Yanamadala, Vijay; Shin, John H

2015-12-01

We report an intramedullary spinal cord metastasis from a bronchial carcinoid, and discuss its mechanisms and management. Intramedullary spinal cord metastases from any cancer are rare, and bronchial carcinoids account for only a small fraction of lung cancers. To our knowledge, an intramedullary spinal cord metastasis from a bronchial carcinoid has been described only once previously. Copyright © 2015 Elsevier Ltd. All rights reserved.

Calcineurin Dysregulation Underlies Spinal Cord Injury-Induced K+ Channel Dysfunction in DRG Neurons

PubMed Central

Zemel, Benjamin M.; Brown, Eric V.; Urban, Mark W.; Tymanskyj, Stephen R.; Lepore, Angelo C.

2017-01-01

Dysfunction of the fast-inactivating Kv3.4 potassium current in dorsal root ganglion (DRG) neurons contributes to the hyperexcitability associated with persistent pain induced by spinal cord injury (SCI). However, the underlying mechanism is not known. In light of our previous work demonstrating modulation of the Kv3.4 channel by phosphorylation, we investigated the role of the phosphatase calcineurin (CaN) using electrophysiological, molecular, and imaging approaches in adult female Sprague Dawley rats. Pharmacological inhibition of CaN in small-diameter DRG neurons slowed repolarization of the somatic action potential (AP) and attenuated the Kv3.4 current. Attenuated Kv3.4 currents also exhibited slowed inactivation. We observed similar effects on the recombinant Kv3.4 channel heterologously expressed in Chinese hamster ovary cells, supporting our findings in DRG neurons. Elucidating the molecular basis of these effects, mutation of four previously characterized serines within the Kv3.4 N-terminal inactivation domain eliminated the effects of CaN inhibition on the Kv3.4 current. SCI similarly induced concurrent Kv3.4 current attenuation and slowing of inactivation. Although there was little change in CaN expression and localization after injury, SCI induced upregulation of the native regulator of CaN 1 (RCAN1) in the DRG at the transcript and protein levels. Consistent with CaN inhibition resulting from RCAN1 upregulation, overexpression of RCAN1 in naive DRG neurons recapitulated the effects of pharmacological CaN inhibition on the Kv3.4 current and the AP. Overall, these results demonstrate a novel regulatory pathway that links CaN, RCAN1, and Kv3.4 in DRG neurons. Dysregulation of this pathway might underlie a peripheral mechanism of pain sensitization induced by SCI. SIGNIFICANCE STATEMENT Pain sensitization associated with spinal cord injury (SCI) involves poorly understood maladaptive modulation of neuronal excitability. Although central mechanisms have received significant attention, recent studies have identified peripheral nerve hyperexcitability as a driver of persistent pain signaling after SCI. However, the ion channels and signaling molecules responsible for this change in primary sensory neuron excitability are still not well defined. To address this problem, this study used complementary electrophysiological and molecular methods to determine how Kv3.4, a voltage-gated K+ channel robustly expressed in dorsal root ganglion neurons, becomes dysfunctional upon calcineurin (CaN) inhibition. The results strongly suggest that CaN inhibition underlies SCI-induced dysfunction of Kv3.4 and the associated excitability changes through upregulation of the native regulator of CaN 1 (RCAN1). PMID:28751455

JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain

PubMed Central

Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R.; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

2009-01-01

Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, TNF-α transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-α/JNK pathway. MCP-1 upregulation by TNF-α was dose-dependently inhibited by the JNK inhibitors SP600125 and D-JNKI-1. Spinal injection of TNF-α produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Further, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase (ERK) in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous excitatory synaptic currents (sEPSCs) but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Taken together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes following JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management. PMID:19339605

Nanog interact with CDK6 to regulates astrocyte cells proliferation following spinal cord injury

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

Gu, Jun; Department of Orthopaedics, Xishan People's Hospital, Wuxi, Jiangsu; Ni, Yingjie

2016-01-22

Previous research had reported transcription factors Nanog expressed in pluripotent embryonic stem cells (ESCS) that played an important role in regulating the cell proliferation. Nanog levels are frequently elevated in ESCS, but the role in the spinal cord was not clear. To examine the biological relevance of Nanog, we studied its properties in spinal cord injury model. The expression of Nanog and PCNA was gradually increased and reached a peak at 3 day by western blot analysis. The expression of Nanog was further analyzed by immunohistochemistry. Double immunofluorescent staining uncovered that Nanog can co-labeled with PCNA and GFAP in themore » spinal cord tissue. In vitro, Nanog can promote the proliferation of astrocyte cell by Fluorescence Activating Cell Sorter (FACS) and CCK8. Meanwhile, the cell-cycle protein CDK6 could interact with Nanog in the spinal cord tissue. Taken together, these data suggested that both Nanog may play important roles in spinal cord pathophysiology via interact with CDK6.« less

Minimally Invasive Drainage of a Post-Laminectomy Subfascial Seroma with Cervical Spinal Cord Compression.

PubMed

Kitshoff, Adriaan Mynhardt; Van Goethem, Bart; Cornelis, Ine; Combes, Anais; Dvm, Ingeborgh Polis; Gielen, Ingrid; Vandekerckhove, Peter; de Rooster, Hilde

2016-01-01

A 14 mo old female neutered Doberman pinscher was evaluated for difficulty in rising, a wide based stance, pelvic limb gait abnormalities, and cervical pain of 2 mo duration. Neurologic examination revealed pelvic limb ataxia and cervical spinal hyperesthesia. Spinal reflexes and cranial nerve examination were normal. The pathology was localized to the C1-C5 or C6-T2 spinal cord segments. Computed tomography (CT) findings indicated bony proliferation of the caudal articular processes of C6 and the cranial articular processes of C7, resulting in bilateral dorsolateral spinal cord compression that was more pronounced on the left side. A limited dorsal laminectomy was performed at C6-C7. Due to progressive neurological deterioration, follow-up CT examination was performed 4 days postoperatively. At the level of the laminectomy defect, a subfacial seroma had developed, entering the spinal canal and causing significant spinal cord compression. Under ultrasonographic guidance a closed-suction wound catheter was placed. Drainage of the seroma successfully relieved its compressive effects on the spinal cord and the patient's neurological status improved. CT was a valuable tool in assessing spinal cord compression as a result of a postoperative subfascial seroma. Minimally invasive application of a wound catheter can be successfully used to manage this condition.

Extended magnetic resonance imaging studies on the effect of classically activated microglia transplantation on white matter regeneration following spinal cord focal injury in adult rats

PubMed Central

Marcol, Wiesław; Ślusarczyk, Wojciech; Larysz-Brysz, Magdalena; Łabuzek, Krzysztof; Kapustka, Bartosz; Staszkiewicz, Rafał; Rosicka, Paulina; Kalita, Katarzyna; Węglarz, Władysław; Lewin-Kowalik, Joanna

2017-01-01

Spinal cord injuries are still a serious problem for regenerative medicine. Previous research has demonstrated that activated microglia accumulate in spinal lesions, influencing the injured tissues in various ways. Therefore, transplantation of activated microglia may have a beneficial role in the regeneration of the nervous system. The present study examined the influence of transplanted activated microglial cells in adult rats with injured spinal cords. Rats were randomly divided into an experimental (M) and control (C) group, and were subjected to non-laminectomy focal injury of spinal cord white matter by means of a high-pressured air stream. In group M, activated cultured microglial cells were injected twice into the site of injury. Functional outcome and morphological features of regeneration were analyzed during a 12-week follow-up. The lesions were characterized by means of magnetic resonance imaging (MRI). Neurons in the brain stem and motor cortex were labeled with FluoroGold (FG). A total of 12 weeks after surgery, spinal cords and brains were collected and subjected to histopathological and immunohistochemical examinations. Lesion sizes in the spinal cord were measured and the number of FG-positive neurons was counted. Rats in group M demonstrated significant improvement of locomotor performance when compared with group C (P<0.05). MRI analysis demonstrated moderate improvement in water diffusion along the spinal cord in the group M following microglia treatment, as compared with group C. The water diffusion perpendicular to the spinal cord in group M was closer to the reference values for a healthy spinal cord than it was in group C. The sizes of lesions were also significantly smaller in group M than in the group C (P<0.05). The number of brain stem and motor cortex FG-positive neurons in group M was significantly higher than in group C. The present study demonstrated that delivery of activated microglia directly into the injured spinal cord gives some positive effects for the regeneration of the white matter. PMID:29201191

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

PubMed

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

2015-02-01

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

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

PubMed

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

2003-12-01

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

The Role of Brain-Derived Neurotrophic Factor (BDNF) in the Development of Neurogenic Detrusor Overactivity (NDO)

PubMed Central

Frias, Bárbara; Santos, João; Morgado, Marlene; Sousa, Mónica Mendes; Gray, Susannah M.Y.; McCloskey, Karen D.; Allen, Shelley; Cruz, Francisco

2015-01-01

Neurogenic detrusor overactivity (NDO) is a well known consequence of spinal cord injury (SCI), recognizable after spinal shock, during which the bladder is areflexic. NDO emergence and maintenance depend on profound plastic changes of the spinal neuronal pathways regulating bladder function. It is well known that neurotrophins (NTs) are major regulators of such changes. NGF is the best-studied NT in the bladder and its role in NDO has already been established. Another very abundant neurotrophin is BDNF. Despite being shown that, acting at the spinal cord level, BDNF is a key mediator of bladder dysfunction and pain during cystitis, it is presently unclear if it is also important for NDO. This study aimed to clarify this issue. Results obtained pinpoint BDNF as an important regulator of NDO appearance and maintenance. Spinal BDNF expression increased in a time-dependent manner together with NDO emergence. In chronic SCI rats, BDNF sequestration improved bladder function, indicating that, at later stages, BDNF contributes NDO maintenance. During spinal shock, BDNF sequestration resulted in early development of bladder hyperactivity, accompanied by increased axonal growth of calcitonin gene-related peptide-labeled fibers in the dorsal horn. Chronic BDNF administration inhibited the emergence of NDO, together with reduction of axonal growth, suggesting that BDNF may have a crucial role in bladder function after SCI via inhibition of neuronal sprouting. These findings highlight the role of BDNF in NDO and may provide a significant contribution to create more efficient therapies to manage SCI patients. PMID:25653370

Shriners Hospital Spinal Cord Injury Self Care Manual.

ERIC Educational Resources Information Center

Fox, Carol

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

Compressive mechanical characterization of non-human primate spinal cord white matter.

PubMed

Jannesar, Shervin; Allen, Mark; Mills, Sarah; Gibbons, Anne; Bresnahan, Jacqueline C; Salegio, Ernesto A; Sparrey, Carolyn J

2018-05-02

The goal of developing computational models of spinal cord injury (SCI) is to better understand the human injury condition. However, finite element models of human SCI have used rodent spinal cord tissue properties due to a lack of experimental data. Central nervous system tissues in non human primates (NHP) closely resemble that of humans and therefore, it is expected that material constitutive models obtained from NHPs will increase the fidelity and the accuracy of human SCI models. Human SCI most often results from compressive loading and spinal cord white matter properties affect FE predicted patterns of injury; therefore, the objectives of this study were to characterize the unconfined compressive response of NHP spinal cord white matter and present an experimentally derived, finite element tractable constitutive model for the tissue. Cervical spinal cords were harvested from nine male adult NHPs (Macaca mulatta). White matter biopsy samples (3 mm in diameter) were taken from both lateral columns of the spinal cord and were divided into four strain rate groups for unconfined dynamic compression and stress relaxation (post-mortem <1-hour). The NHP spinal cord white matter compressive response was sensitive to strain rate and showed substantial stress relaxation confirming the viscoelastic behavior of the material. An Ogden 1st order model best captured the non-linear behavior of NHP white matter in a quasi-linear viscoelastic material model with 4-term Prony series. This study is the first to characterize NHP spinal cord white matter at high (>10/sec) strain rates typical of traumatic injury. The finite element derived material constitutive model of this study will increase the fidelity of SCI computational models and provide important insights for transferring pre-clinical findings to clinical treatments. Spinal cord injury (SCI) finite element (FE) models provide an important tool to bridge the gap between animal studies and human injury, assess injury prevention technologies (e.g. helmets, seatbelts), and provide insight into the mechanisms of injury. Although, FE model outcomes depend on the assumed material constitutive model, there is limited experimental data for fresh spinal cords and all was obtained from rodent, porcine or bovine tissues. Central nervous system tissues in non human primates (NHP) more closely resemble humans. This study characterizes fresh NHP spinal cord material properties at high strains rates and large deformations typical of SCI for the first time. A constitutive model was defined that can be readily implemented in finite strain FE analysis of SCI. Copyright © 2018. Published by Elsevier Ltd.

[Spinal cord injury with neurogenic lower urinary tract dysfunction as a potential risk factor for bladder carcinoma].

PubMed

Böthig, Ralf; Fiebag, Kai; Kowald, Birgitt; Hirschfeld, Sven; Thietje, Roland; Kurze, Ines; Schöps, Wolfgang; Böhme, Holger; Kaufmann, Albert; Zellner, Michael; Kadhum, Thura; Golka, Klaus

2018-05-29

 Life expectancy for people with spinal cord injury/disease (SCI/D) is increasing, due to modern advances in treatment methods and in neuro-urology. However, with the increased life expectancy the risk of developing urinary bladder cancer is gaining importance. How is this patient group different from the general population?  Single-centre retrospective evaluation of consecutive patient data with spinal cord injury and proven urinary bladder cancer.  Between January 1st 1998 and March 31st 2017, 32 (3 female, 29 male) out of a total of 6432 patients with SCI/D were diagnosed with bladder cancer.The average age at bladder cancer diagnosis was 54.5 years, which is well below the average for bladder cancer cases in the general population (male: 74, female: 75).Twenty-seven patients suffered from urodynamically confirmed neurogenic detrusor overactivity, while five patients (all male) had detrusor acontractility.The median latency period between the onset of SCI/D and tumor diagnosis was 29.5 years. Temporary indwelling catheterisation was found in four patients for only 1.61 % of the overall latency period of all patients.The majority of the patients (n = 27) had transitional cell carcinoma, while five had squamous cell carcinoma. Of the 32 patients, 25 (78 %) had muscle invasive bladder cancer at ≥ T2 at the time of diagnosis. Regarding tumour grading, 23 out of 32 patients showed a histologically poorly differentiated G3 carcinoma; two patients each had G2 and G1 tumours repectively (no information on tumour grading was available in five patients).The median survival for all patients was 11.5 months. The prognosis of patients with squamous cell carcinoma was even worse; 4 out of 5 died within 7 months (median 4 months).  The significantly younger age at onset and the frequency of invasive, poorly differentiated tumour at diagnosis indicate that SCI/D influences both bladder cancer risk and prognosis significantly. The latency period between paralysis and tumour disease seems to be a decisive risk parameter.The type of neurogenic bladder dysfunction and the form of bladder drainage do not appear to influence the risk. Long-term indwelling catheter drainage played only a minor role in the investigated patients.Early detection of bladder cancer in patients with spinal cord injury remains a challenge. © Georg Thieme Verlag KG Stuttgart · New York.

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

PubMed

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

2014-01-01

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

Magnetic resonance diffusion tensor imaging of cervical spinal cord and lumbosacral enlargement in patients with cervical spondylotic myelopathy.

PubMed

Chen, Xueming; Kong, Chao; Feng, Shiqing; Guan, Hua; Yu, Zhenshan; Cui, Libin; Wang, Yanhui

2016-06-01

To identify the correlations of diffusion tensor imaging (DTI) indices between the cervical spinal cord and lumbosacral enlargement in healthy volunteers and patients with cervical spondylotic myelopathy (CSM). DTI was performed at the cervical spinal cord and lumbosacral enlargement in 10 CSM patients and 10 volunteers at 1.5T. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of were measured and compared between CSM patients and volunteers. DTI indices of different cervical segments in volunteers were compared. DTI indices of the cervical spinal cord were correlated with those of the lumbosacral enlargement. In healthy subjects, DTI indices of different cervical cord sections showed no significant difference (ADC: F = 0.62; P = 0.65; FA: F = 1.228; P = 0.312); there was no correlation between the DTI indices of the cervical spinal cord and those of the lumbosacral enlargement (ADC: r = 0.442, P = 0.201; FA: r = -0.054, P = 0.881). In the CSM patients, the ADC value significantly increased, while the FA value significantly decreased in the cervical spinal cord (ADC: P = 0.002; FA: P < 0.001) and lumbosacral enlargement (ADC: P = 0.003; FA: P < 0.001) compared with the healthy group. Both DTI indices showed no correlation between the cervical spinal cord and those of the lumbosacral enlargement in the CSM group (ADC: r = -0.052, P = 0.887; FA: r = 0.129, P = 0.722). The ADC value of the cervical spinal cord and lumbosacral enlargement in CSM patients showed significant increase compared with healthy volunteers, while the FA value significantly decreased. Both DTI indices of the cervical spinal cord had no linear correlation with those of the lumbosacral enlargement. J. Magn. Reson. Imaging 2016;43:1484-1491. © 2015 Wiley Periodicals, Inc.

Morphology of the caudal spinal cord in Rana (Ranidae) and Xenopus (Pipidae) tadpoles.

PubMed

Nishikawa, K; Wassersug, R

1988-03-08

Using a variety of neuroanatomical and histological techniques, we compare the spinal cord and peripheral nerve distribution in the tails of larvae from Xenopus laevis and three species of Rana. The relatively large, postsacral spinal cord of Xenopus contains abundant motoneurons and their axons. Spinal nerves exit from the spinal cord in a regular array, one nerve per myotome, from the cervical region to near the end of the tail. Somata of motoneurons innervating caudal myotomes are found along the entire length of the tail. In contrast, the caudal cord of Rana is reduced to a filum terminale consisting of little more than an ependymal tube; spinal nerves to all caudal myotomes leave the cord in the sacral region and reach their motor targets via a cauda equina and caudal plexus. Motoneuron cell bodies innervating caudal myotomes are found only in the sacral region. The Rana larval pattern is similar to that of adult frogs and mammals, whereas the Xenopus larval pattern is more like that of salamanders and reptiles. These gross neuroanatomical differences are not due to differences in the size or developmental stage of the tadpoles, but instead are associated with differences in the swimming behavior of the larvae. The presence of motoneurons in the caudal spinal cord of Xenopus may provide local intermyotomal control within the tail; the elongated topography of the cord appears to permit finer, rostral-to-caudal regulation of neuromuscular activity. The Rana spinal cord, on the other hand--with motoneurons clustered anteriorly--may produce concurrent firing of adjacent ipsilateral myotomes, but at the expense of fine intermyotomal regulation. The fact that nerves in the tail of Xenopus enter and exit from the spinal cord locally, as opposed to far anteriorly as in Rana, means that for tadpoles of the same size, reflex arc lengths are many times shorter in Xenopus.

A single dose of a neuron-binding human monoclonal antibody improves brainstem NAA concentrations, a biomarker for density of spinal cord axons, in a model of progressive multiple sclerosis.

PubMed

Wootla, Bharath; Denic, Aleksandar; Watzlawik, Jens O; Warrington, Arthur E; Rodriguez, Moses

2015-04-29

Intracerebral infection of susceptible mouse strains with Theiler's murine encephalomyelitis virus (TMEV) results in chronic demyelinating disease with progressive axonal loss and neurologic dysfunction similar to progressive forms of multiple sclerosis (MS). We previously showed that as the disease progresses, a marked decrease in brainstem N-acetyl aspartate (NAA; metabolite associated with neuronal integrity) concentrations, reflecting axon health, is measured. We also demonstrated stimulation of neurite outgrowth by a neuron-binding natural human antibody, IgM12. Treatment with either the serum-derived or recombinant human immunoglobulin M 12 (HIgM12) preserved functional motor activity in the TMEV model. In this study, we examined IgM-mediated changes in brainstem NAA concentrations and central nervous system (CNS) pathology. (1)H-magnetic resonance spectroscopy (MRS) showed that treatment with HIgM12 significantly increased brainstem NAA concentrations compared to controls in TMEV-infected mice. Pathologic analysis demonstrated a significant preservation of axons in the spinal cord of animals treated with HIgM12. This study links drug efficacy of slowing deficits with axon preservation and NAA concentrations in the brainstem in a model of progressive MS. HIgM12-mediated changes of NAA concentrations in the brainstem are a surrogate marker of axon injury/preservation throughout the spinal cord. This study provides proof-of-concept that a neuron-reactive human IgM can be therapeutic and provides a biomarker for clinical trials.

A combined deficiency of vitamins E and C causes severe central nervous system damage in guinea pigs.

PubMed

Burk, Raymond F; Christensen, Joani M; Maguire, Mark J; Austin, Lori M; Whetsell, William O; May, James M; Hill, Kristina E; Ebner, Ford F

2006-06-01

A short period of combined deficiency of vitamins E and C causes profound central nervous system (CNS) dysfunction in guinea pigs. For this report, CNS histopathology was studied to define the nature and extent of injury caused by this double deficiency. Weanling guinea pigs were fed a vitamin E-deficient or -replete diet for 14 d. Then vitamin C was withdrawn from the diet of some guinea pigs. Four diet groups were thus formed: replete, vitamin E deficient, vitamin C deficient, and both vitamin E and C deficient. From 5 to 11 d after institution of the doubly deficient diet, 9 of 12 guinea pigs developed paralysis, and 2 more were found dead. The remaining guinea pig in the doubly deficient group and all animals in the other 3 groups survived without clinical impairment until the experiment was terminated at 13-15 d. Brains and spinal cords were serially sectioned and stained for examination. Only the combined deficiency produced damage in the CNS. The damage consisted mainly of nerve cell death, axonal degeneration, vascular injury, and associated glial cell responses. The spinal cord and the ventral pons in the brainstem were most severely affected, often exhibiting asymmetric cystic lesions. Several features of the lesions suggest that the primary damage was to blood vessels. These results indicate that the paralysis and death caused by combined deficiency of vitamins E and C in guinea pigs is caused by severe damage in the brainstem and spinal cord.

Alterations in Mouse Hypothalamic Adipokine Gene Expression and Leptin Signaling following Chronic Spinal Cord Injury and with Advanced Age

PubMed Central

Bigford, Gregory E.; Bracchi-Ricard, Valerie C.; Nash, Mark S.; Bethea, John R.

2012-01-01

Chronic spinal cord injury (SCI) results in an accelerated trajectory of several cardiovascular disease (CVD) risk factors and related aging characteristics, however the molecular mechanisms that are activated have not been explored. Adipokines and leptin signaling are known to play a critical role in neuro-endocrine regulation of energy metabolism, and are now implicated in central inflammatory processes associated with CVD. Here, we examine hypothalamic adipokine gene expression and leptin signaling in response to chronic spinal cord injury and with advanced age. We demonstrate significant changes in fasting-induced adipose factor (FIAF), resistin (Rstn), long-form leptin receptor (LepRb) and suppressor of cytokine-3 (SOCS3) gene expression following chronic SCI and with advanced age. LepRb and Jak2/stat3 signaling is significantly decreased and the leptin signaling inhibitor SOCS3 is significantly elevated with chronic SCI and advanced age. In addition, we investigate endoplasmic reticulum (ER) stress and activation of the uncoupled protein response (UPR) as a biological hallmark of leptin resistance. We observe the activation of the ER stress/UPR proteins IRE1, PERK, and eIF2alpha, demonstrating leptin resistance in chronic SCI and with advanced age. These findings provide evidence for adipokine-mediated inflammatory responses and leptin resistance as contributing to neuro-endocrine dysfunction and CVD risk following SCI and with advanced age. Understanding the underlying mechanisms contributing to SCI and age related CVD may provide insight that will help direct specific therapeutic interventions. PMID:22815920

Positive and negative affect in individuals with spinal cord injuries.

PubMed

Salter, J E; Smith, S D; Ethans, K D

2013-03-01

Participants with spinal cord injuries (SCIs) and healthy controls completed standardized questionnaires assessing depression level, positive and negative affect, and personality traits. To identify the specific characteristics of emotional experiences affected by spinal cord injury. A Canadian rehabilitation center. Individuals with SCIs were recruited from a list of patients who had volunteered to participate in studies being conducted by the SCI clinic. Healthy controls were recruited from the community, but tested in the SCI clinic. Thirty-six individuals with complete (ASIA A) SCIs and 36 age-, gender- and education-matched controls participated in this study. SCI participants were classified as cervical (C1-C7), upper thoracic (T1-T5) or lower thoracic/upper lumbar (T6-L2). All participants completed the Beck Depression Inventory, the Positive and Negative Affect Schedules, the NEO Neuroticism Questionnaire, and the harm avoidance scale of the Tridimensional Personality Questionnaire. Data were analyzed using independent-samples t-tests (when contrasting SCI and controls) and analysis of variance (when comparing across SCI groups). Participants with SCIs experienced significantly less positive affect than controls. The two groups did not differ in their experience of negative affect. Participants with SCIs also reported greater levels of depression. Depression scores improved with an increasing number of years post injury. Individuals with SCIs are characterized by specific emotional dysfunction related to the experience of positive emotions, rather than a tendency to ruminate on negative emotions. The results suggest that these individuals would benefit from rehabilitation programs that include training in positive psychology.

Nonlinear optical techniques for imaging and manipulating the mouse central nervous system

NASA Astrophysics Data System (ADS)

Farrar, Matthew John

The spinal cord of vertebrates serves as the conduit for somatosensory information and motor control, as well as being the locus of neural circuits that govern fast reflexes and patterned behaviors, such as walking in mammals or swimming in fish. Consequently, pathologies of the spinal cord -such as spinal cord injury (SCI)- lead to loss of motor control and sensory perception, with accompanying decline in life expectancy and quality of life. Despite the devastating effects of these diseases, few therapies exist to substantially ameliorate patient outcome. In part, studies of spinal cord pathology have been limited by the inability to perform in vivo imaging at the level of cellular processes. The focus of this thesis is to present the underlying theory for and demonstration of novel multi-photon microscopy (MPM) and optical manipulation techniques as they apply to studies the mouse central nervous system (CNS), with an emphasis on the spinal cord. The scientific findings which have resulted from the implementation of these techniques are also presented. In particular, we have demonstrated that third harmonic generation is a dye-free method of imaging CNS myelin, a fundamental constituent of the spinal cord that is difficult to label using exogenous dyes and/or transgenic constructs. Since gaining optical access to the spinal cord is a prerequisite for spinal cord imaging, we review our development of a novel spinal cord imaging chamber and surgical procedure which allowed us to image for multiple weeks following implantation without the need for repeated surgeries. We also have used MPM to characterize spinal venous blood flow before and after point occlusions. We review a novel nonlinear microscopy technique that may serve to show optical interfaces in three dimensions inside scattering tissue. Finally, we discuss a model and show results of optoporation, a means of transfecting cells with genetic constructs. Brief reviews of MPM and SCI are also presented.

Spinal Meninges and Their Role in Spinal Cord Injury: A Neuroanatomical Review.

PubMed

Grassner, Lukas; Grillhösl, Andreas; Griessenauer, Christoph J; Thomé, Claudius; Bühren, Volker; Strowitzki, Martin; Winkler, Peter A

2018-02-01

Current recommendations support early surgical decompression and blood pressure augmentation after traumatic spinal cord injury (SCI). Elevated intraspinal pressure (ISP), however, has probably been underestimated in the pathophysiology of SCI. Recent studies provide some evidence that ISP measurements and durotomy may be beneficial for individuals suffering from SCI. Compression of the spinal cord against the meninges in SCI patients causes a "compartment-like" syndrome. In such cases, intentional durotomy with augmentative duroplasty to reduce ISP and improve spinal cord perfusion pressure (SCPP) may be indicated. Prior to performing these procedures routinely, profound knowledge of the spinal meninges is essential. Here, we provide an in-depth review of relevant literature along with neuroanatomical illustrations and imaging correlates.

Neurologic outcome after thoracolumbar partial lateral corpectomy for intervertebral disc disease in 72 dogs.

PubMed

Salger, Florian; Ziegler, Luisa; Böttcher, Irene Christine; Oechtering, Gerhard; Böttcher, Peter; Flegel, Thomas

2014-07-01

To determine neurologic outcome and factors influencing outcome after thoracolumbar partial lateral corpectomy (PLC) in dogs with intervertebral disc disease (IVDD) causing ventral spinal cord compression. Retrospective case series. Dogs with IVDD (n = 72; 87 PLC). Dogs with IVDD between T9 and L5 were included if treated by at least 1 PLC. Exclusion criteria were: previous spinal surgery, combination of PLC with another surgical procedure. Neurologic outcome was assessed by: (1) modified Frankel score (MFS) based on neurologic examinations at 4 time points (before surgery, immediately after PLC, at discharge and 4 weeks after PLC); and (2) owner questionnaire. The association of the following factors with neurologic outcome was analyzed: age, body weight, duration of current neurologic dysfunction (acute, chronic), IVDD localization, breed (chondrodystrophic, nonchondrodystrophic), number of PLCs, degree of presurgical spinal cord compression and postsurgical decompression, slot depth, presurgical MFS. Presurgical spinal cord compression was determined by CT myelography (71 dogs) or MRI (1 dog), whereas postsurgical decompression and slot depth were determined on CT myelography (69 dogs). MFS was improved in 18.7%, 31.7%, and 64.2% of dogs at the 3 postsurgical assessments, whereas it was unchanged in 62.6%, 52.8%, and 32.0% at corresponding time points. Based on owner questionnaire, 91.4% of dogs were ambulatory 6 months postsurgically with 74.5% having a normal gait. Most improvement in neurologic function developed within 6 months after surgery. Presurgical MFS was the only variable significantly associated with several neurologic outcome measurements (P < .01). PLC is an option for decompression in ventrally compressing thoracolumbar IVDD. Prognosis is associated with presurgical neurologic condition. © Copyright 2014 by The American College of Veterinary Surgeons.

New insights into the mechanisms of itch: are pain and itch controlled by distinct mechanisms?

PubMed Central

Liu, Tong; Ji, Ru-Rong

2013-01-01

Itch and pain are closely related but distinct sensations. They share largely overlapping mediators and receptors, and itch-responding neurons are also sensitive to pain stimuli. Itch-mediating primary sensory neurons are equipped with distinct receptors and ion channels for itch transduction, including Mas-related G protein-coupled receptors (Mrgprs), protease-activated receptors (PARs), histamine receptors, bile acid receptor (TGR5), toll-like receptors (TLRs), and transient receptor potential subfamily V1/A1 (TRPV1/A1). Recent progress has indicated the existence of an itch-specific neuronal circuitry. The MrgprA3-expressing primary sensory neurons exclusively innervate the epidermis of skin and their central axons connect with gastrin-releasing peptide receptor (GRPR)-expressing neurons in the superficial spinal cord. Notably, ablation of MrgprA3-expressing primary sensory neurons or GRPR-expressing spinal cord neurons results in selective reduction in itch but not pain. Chronic itch results from dysfunction of the immune and nervous system and can manifest as neural plasticity, despite the fact that chronic itch is often treated by dermatologists. While differences between acute pain and acute itch are striking, chronic itch and chronic pain share many similar mechanisms, including peripheral sensitization (increased responses of primary sensory neurons to itch and pain mediators), central sensitization (hyperactivity of spinal projection neurons and excitatory interneurons), loss of inhibitory control in the spinal cord, and neuro-immune and neuro-glial interactions. Notably, painful stimuli can elicit itch in some chronic conditions (e.g., atopic dermatitis) and some drugs for treating chronic pain are also effective in chronic itch. Thus, itch and pain have more similarities in pathological and chronic conditions. PMID:23636773

Degeneration of Phrenic Motor Neurons Induces Long-Term Diaphragm Deficits following Mid-Cervical Spinal Contusion in Mice

PubMed Central

Nicaise, Charles; Putatunda, Rajarshi; Hala, Tamara J.; Regan, Kathleen A.; Frank, David M.; Brion, Jean-Pierre; Leroy, Karelle; Pochet, Roland; Wright, Megan C.

2012-01-01

Abstract A primary cause of morbidity and mortality following cervical spinal cord injury (SCI) is respiratory compromise, regardless of the level of trauma. In particular, SCI at mid-cervical regions targets degeneration of both descending bulbospinal respiratory axons and cell bodies of phrenic motor neurons, resulting in deficits in the function of the diaphragm, the primary muscle of inspiration. Contusion-type trauma to the cervical spinal cord is one of the most common forms of human SCI; however, few studies have evaluated mid-cervical contusion in animal models or characterized consequent histopathological and functional effects of degeneration of phrenic motor neuron–diaphragm circuitry. We have generated a mouse model of cervical contusion SCI that unilaterally targets both C4 and C5 levels, the location of the phrenic motor neuron pool, and have examined histological and functional outcomes for up to 6 weeks post-injury. We report that phrenic motor neuron loss in cervical spinal cord, phrenic nerve axonal degeneration, and denervation at diaphragm neuromuscular junctions (NMJ) resulted in compromised ipsilateral diaphragm function, as demonstrated by persistent reduction in diaphragm compound muscle action potential amplitudes following phrenic nerve stimulation and abnormalities in spontaneous diaphragm electromyography (EMG) recordings. This injury paradigm is reproducible, does not require ventilatory assistance, and provides proof-of-principle that generation of unilateral cervical contusion is a feasible strategy for modeling diaphragmatic/respiratory deficits in mice. This study and its accompanying analyses pave the way for using transgenic mouse technology to explore the function of specific genes in the pathophysiology of phrenic motor neuron degeneration and respiratory dysfunction following cervical SCI. PMID:23176637

Childhood Brain and Spinal Cord Tumors Treatment Overview (PDQ®)—Patient Version

Cancer.gov

Brain and spinal cord tumors may be benign (not cancer) or malignant (cancer). Both types cause signs or symptoms and need treatment. Get information about the many kinds of brain and spinal cord tumors, signs and symptoms, tests to diagnose, and treatment in this expert-reviewed summary.

34 CFR 359.10 - What types of projects are authorized under this program?

Code of Federal Regulations, 2010 CFR

2010-07-01

... rehabilitation services to individuals with spinal cord injuries; and (b) Conduct spinal cord research, including clinical research and the analysis of standardized data in collaboration with other related projects... REHABILITATION RESEARCH: SPECIAL PROJECTS AND DEMONSTRATIONS FOR SPINAL CORD INJURIES What Kinds of Activities...

Microsurgical resection of intramedullary spinal cord hemangioblastoma.

PubMed

McCormick, Paul C

2014-09-01

Spinal cord hemangioblastomas account for about 10% of spinal cord tumors. They usually arise from the dorsolateral pia mater and are characterized by their significant vascularity. The principles and techniques of safe resection are different than those employed for the more commonly occurring intramedullary glial tumors (e.g. ependymoma, astrocytoma) and consist of circumferential detachment of the tumor margin from the surrounding normal pia. This video demonstrates the microsurgical techniques of resection of a thoracic spinal cord hemangioblastoma. The video can be found here: http://youtu.be/yT5KLi4VyAo.

Life satisfaction in patients with and without spinal cord ischemia after advanced endovascular therapy for extensive aortic disease at mid-term follow-up.

PubMed

Mehmedagic, Irma; Santén, Stefan; Jörgensen, Sophie; Acosta, Stefan

2016-11-11

Advanced endovascular aortic repair can be used to treat patients with extensive and complex aortic disease who are at risk of spinal cord ischaemia. The aim of this study was to compare whether life satisfaction differs between patients with and without spinal cord ischaemia at mid-term follow-up. Nested case-control study. Among patients undergoing advanced endovascular aortic repair between 2009 and 2012, 18 patients with spinal cord ischaemia and 33 without were interviewed at home. The Life Satisfaction Questionnaire (LiSat-11) and the Satisfaction With Life Scale (SWLS) were used. LiSat-11 found that patients with spinal cord ischaemia were more dissatisfied with their activities of daily living than were patients without spinal cord ischaemia (p=0.012). Both groups had similar, very low, scores in the sexual life domain; median 2.0 (interquartile range (IQR) 1.5-3.0) and 3.0 (IQR 2.0-4.0), respectively. There was no difference in SWLS between the groups. This study cohort of patients who underwent advanced endovascular aortic repair was rather homo-genous in their rating of life satisfaction and there was little difference between mid-term survivors who had spinal cord ischaemia and those who did not.

Serum leptin, bone mineral density and the healing of long bone fractures in men with spinal cord injury.

PubMed

Wang, Lei; Liu, Linjuan; Pan, Zhanpeng; Zeng, Yanjun

2015-11-16

Previously reported fracture rates in patients with spinal cord injury range from 1% to 20%. However, the exact role of spinal cord injury in bone metabolism has not yet been clarified. In order to investigate the effects of serum leptin and bone mineral density on the healing of long bone fractures in men with spinal cord injury, 15 male SCI patients and 15 matched controls were involved in our study. The outcome indicated that at 4 and 8 weeks after bone fracture, callus production in patients with spinal cord injury was lower than that in controls. Besides, bone mineral density was significantly reduced at 2, 4 and 8 weeks. In addition, it was found that at each time point, patients with spinal cord injury had significantly higher serum leptin levels than controls and no association was found between serum leptin level and bone mineral density of lumbar vertebrae. Moreover, bone mineral density was positively correlated with bone formation in both of the groups. These findings suggest that in early phases i.e. week 4 and 8, fracture healing was impaired in patients with spinal cord injury and that various factors participated in the complicated healing process, such as hormonal and mechanical factors.

Technique of spinal cord compression induced by inflation of epidural balloon catheter in rabbits (Oryctologus cuniculus): efficient and easy to use model.

PubMed

Fonseca, Antonio F B DA; Scheffer, Jussara P; Coelho, Barbara P; Aiello, Graciane; Guimarães, Arthur G; Gama, Carlos R B; Vescovini, Victor; Cabral, Paula G A; Oliveira, André L A

2016-09-01

The most common cause of spinal cord injury are high impact trauma, which often result in some motor impairment, sensory or autonomic a greater or lesser extent in the distal areas the level of trauma. In terms of survival and complications due to sequelae, veterinary patients have a poor prognosis unfavorable. Therefore justified the study of experimental models of spinal cord injury production that could provide more support to research potential treatments for spinal cord injuries in medicine and veterinary medicine. Preclinical studies of acute spinal cord injury require an experimental animal model easily reproducible. The most common experimental animal model is the rat, and several techniques for producing a spinal cord injury. The objective of this study was to describe and evaluate the effectiveness of acute spinal cord injury production technique through inflation of Fogarty(r) catheter using rabbits as an experimental model because it is a species that has fewer conclusive publications and contemplating. The main requirements of a model as low cost, handling convenience, reproducibility and uniformity. The technique was adequate for performing preclinical studies in neuro-traumatology area, effectively leading to degeneration and necrosis of the nervous tissue fostering the emergence of acute paraplegia.

Male rats develop more severe experimental autoimmune encephalomyelitis than female rats: sexual dimorphism and diergism at the spinal cord level.

PubMed

Nacka-Aleksić, Mirjana; Djikić, Jasmina; Pilipović, Ivan; Stojić-Vukanić, Zorica; Kosec, Duško; Bufan, Biljana; Arsenović-Ranin, Nevena; Dimitrijević, Mirjana; Leposavić, Gordana

2015-10-01

Compared with females, male Dark Agouti (DA) rats immunized for experimental autoimmune encephalomyelitis (EAE) with rat spinal cord homogenate in complete Freund's adjuvant (CFA) exhibited lower incidence of the disease, but the maximal neurological deficit was greater in the animals that developed the disease. Consistently, at the peak of the disease greater number of reactivated CD4+CD134+CD45RC- T lymphocytes was retrieved from male rat spinal cord. Their microglia/macrophages were more activated and produced greater amount of prototypic proinflammatory cytokines in vitro. Additionally, oppositely to the expression of mRNAs for IL-12/p35, IL-10 and IL-27/p28, the expression of mRNA for IL-23/p19 was upregulated in male rat spinal cord mononuclear cells. Consequently, the IL-17+:IFN-γ+ cell ratio within T lymphocytes from their spinal cord was skewed towards IL-17+ cells. Within this subpopulation, the IL-17+IFN-γ+:IL-17+IL-10+ cell ratio was shifted towards IL-17+IFN-γ+ cells, which have prominent tissue damaging capacity. This was associated with an upregulated expression of mRNAs for IL-1β and IL-6, but downregulated TGF-β mRNA expression in male rat spinal cord mononuclear cells. The enhanced GM-CSF mRNA expression in these cells supported the greater pathogenicity of IL-17+ T lymphocytes infiltrating male spinal cord. In the inductive phase of the disease, contrary to the draining lymph node, in the spinal cord the frequency of CD134+ cells among CD4+ T lymphocytes and the frequency of IL-17+ cells among T lymphocytes were greater in male than in female rats. This most likely reflected an enhanced transmigration of mononuclear cells into the spinal cord (judging by the lesser spinal cord CXCL12 mRNA expression), the greater frequency of activated microglia/macrophages and the increased expression of mRNAs for Th17 polarizing cytokines in male rat spinal cord mononuclear cells. Collectively, the results showed cellular and molecular mechanisms underlying the target organ specific sexual dimorphism in the T lymphocyte-dependent immune/inflammatory response, and suggested a substantial role for the target organ in shaping the sexually dimorphic clinical outcome of EAE. Copyright © 2015 Elsevier Inc. All rights reserved.

Transverse Myelitis

MedlinePlus

... cord injury to study strategies for replacement or regeneration of spinal cord nerve cells. The knowledge gained from such research should lead ... cord injury to study strategies for replacement or regeneration of spinal cord nerve cells. The knowledge gained from such research should lead ...

Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs.

PubMed

Lim, Ji Hey; Byeon, Ye Eun; Ryu, Hak Hyun; Jeong, Yun Hyeok; Lee, Young Won; Kim, Wan Hee; Kang, Kyung Sun; Kweon, Oh Kyeong

2007-09-01

This study was to determine the effects of allogenic umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) and recombinant methionyl human granulocyte colony-stimulating factor (rmhGCSF) on a canine spinal cord injury model after balloon compression at the first lumbar vertebra. Twenty-five adult mongrel dogs were assigned to five groups according to treatment after a spinal cord injury: no treatment (CN); saline treatment (CP); rmhGCSF treatment (G); UCB-MSCs treatment (UCB-MSC); co-treatment (UCBG). The UCBMSCs isolated from cord blood of canine fetuses were prepared as 10(6) cells/150 microl saline. The UCB-MSCs were directly injected into the injured site of the spinal cord and rmhGCSF was administered subcutaneously 1 week after the induction of spinal cord injury. The Olby score, magnetic resonance imaging, somatosensory evoked potentials and histopathological examinations were used to evaluate the functional recovery after transplantation. The Olby scores of all groups were zero at the 0-week evaluation. At 2 week after the transplantation, the Olby scores in the groups with the UCB-MSC and UCBG were significantly higher than in the CN and CP groups. However, there were no significant differences between the UCB-MSC and UCBG groups, and between the CN and CP groups. These comparisons remained stable at 4 and 8 week after transplantation. There was significant improvement in the nerve conduction velocity based on the somatosensory evoked potentials. In addition, a distinct structural consistency of the nerve cell bodies was noted in the lesion of the spinal cord of the UCB-MSC and UCBG groups. These results suggest that transplantation of the UCB-MSCs resulted in recovery of nerve function in dogs with a spinal cord injury and may be considered as a therapeutic modality for spinal cord injury.

Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs

PubMed Central

Lim, Ji-Hey; Byeon, Ye-Eun; Ryu, Hak-Hyun; Jeong, Yun-Hyeok; Lee, Young-Won; Kim, Wan Hee

2007-01-01

This study was to determine the effects of allogenic umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) and recombinant methionyl human granulocyte colony-stimulating factor (rmhGCSF) on a canine spinal cord injury model after balloon compression at the first lumbar vertebra. Twenty-five adult mongrel dogs were assigned to five groups according to treatment after a spinal cord injury: no treatment (CN); saline treatment (CP); rmhGCSF treatment (G); UCB-MSCs treatment (UCB-MSC); co-treatment (UCBG). The UCB-MSCs isolated from cord blood of canine fetuses were prepared as 106 cells/150 µl saline. The UCB-MSCs were directly injected into the injured site of the spinal cord and rmhGCSF was administered subcutaneously 1 week after the induction of spinal cord injury. The Olby score, magnetic resonance imaging, somatosensory evoked potentials and histopathological examinations were used to evaluate the functional recovery after transplantation. The Olby scores of all groups were zero at the 0-week evaluation. At 2 week after the transplantation, the Olby scores in the groups with the UCB-MSC and UCBG were significantly higher than in the CN and CP groups. However, there were no significant differences between the UCB-MSC and UCBG groups, and between the CN and CP groups. These comparisons remained stable at 4 and 8 week after transplantation. There was significant improvement in the nerve conduction velocity based on the somatosensory evoked potentials. In addition, a distinct structural consistency of the nerve cell bodies was noted in the lesion of the spinal cord of the UCB-MSC and UCBG groups. These results suggest that transplantation of the UCB-MSCs resulted in recovery of nerve function in dogs with a spinal cord injury and may be considered as a therapeutic modality for spinal cord injury. PMID:17679775

Identification of ghost artifact using texture analysis in pediatric spinal cord diffusion tensor images.

PubMed

Alizadeh, Mahdi; Conklin, Chris J; Middleton, Devon M; Shah, Pallav; Saksena, Sona; Krisa, Laura; Finsterbusch, Jürgen; Faro, Scott H; Mulcahey, M J; Mohamed, Feroze B

2018-04-01

Ghost artifacts are a major contributor to degradation of spinal cord diffusion tensor images. A multi-stage post-processing pipeline was designed, implemented and validated to automatically remove ghost artifacts arising from reduced field of view diffusion tensor imaging (DTI) of the pediatric spinal cord. A total of 12 pediatric subjects including 7 healthy subjects (mean age=11.34years) with no evidence of spinal cord injury or pathology and 5 patients (mean age=10.96years) with cervical spinal cord injury were studied. Ghost/true cords, labeled as region of interests (ROIs), in non-diffusion weighted b0 images were segmented automatically using mathematical morphological processing. Initially, 21 texture features were extracted from each segmented ROI including 5 first-order features based on the histogram of the image (mean, variance, skewness, kurtosis and entropy) and 16s-order feature vector elements, incorporating four statistical measures (contrast, correlation, homogeneity and energy) calculated from co-occurrence matrices in directions of 0°, 45°, 90° and 135°. Next, ten features with a high value of mutual information (MI) relative to the pre-defined target class and within the features were selected as final features which were input to a trained classifier (adaptive neuro-fuzzy interface system) to separate the true cord from the ghost cord. The implemented pipeline was successfully able to separate the ghost artifacts from true cord structures. The results obtained from the classifier showed a sensitivity of 91%, specificity of 79%, and accuracy of 84% in separating the true cord from ghost artifacts. The results show that the proposed method is promising for the automatic detection of ghost cords present in DTI images of the spinal cord. This step is crucial towards development of accurate, automatic DTI spinal cord post processing pipelines. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed Central

Eggspuehler, Andreas; Muller, Alfred; Dvorak, Jiri

2007-01-01

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

Endogenous stem cell proliferation induced by intravenous hedgehog agonist administration after contusion in the adult rat spinal cord.

PubMed

Bambakidis, Nicholas C; Horn, Eric M; Nakaji, Peter; Theodore, Nicholas; Bless, Elizabeth; Dellovade, Tammy; Ma, Chiyuan; Wang, Xukui; Preul, Mark C; Coons, Stephen W; Spetzler, Robert F; Sonntag, Volker K H

2009-02-01

Sonic hedgehog (Shh) is a glycoprotein molecule that upregulates the transcription factor Gli1. The Shh protein plays a critical role in the proliferation of endogenous neural precursor cells when directly injected into the spinal cord after a spinal cord injury in adult rodents. Small-molecule agonists of the hedgehog (Hh) pathway were used in an attempt to reproduce these findings through intravenous administration. The expression of Gli1 was measured in rat spinal cord after the intravenous administration of an Hh agonist. Ten adult rats received a moderate contusion and were treated with either an Hh agonist (10 mg/kg, intravenously) or vehicle (5 rodents per group) 1 hour and 4 days after injury. The rats were killed 5 days postinjury. Tissue samples were immediately placed in fixative. Samples were immunohistochemically stained for neural precursor cells, and these cells were counted. Systemic dosing with an Hh agonist significantly upregulated Gli1 expression in the spinal cord (p < 0.005). After spinal contusion, animals treated with the Hh agonist had significantly more nestin-positive neural precursor cells around the rim of the lesion cavity than in vehicle-treated controls (means +/- SDs, 46.9 +/- 12.9 vs 20.9 +/- 8.3 cells/hpf, respectively, p < 0.005). There was no significant difference in the area of white matter injury between the groups. An intravenous Hh agonist at doses that upregulate spinal cord Gli1 transcription also increases the population of neural precursor cells after spinal cord injury in adult rats. These data support previous findings based on injections of Shh protein directly into the spinal cord.

Can the human lumbar posterior columns be stimulated by transcutaneous spinal cord stimulation? A modeling study

PubMed Central

Danner, Simon M.; Hofstoetter, Ursula S.; Ladenbauer, Josef; Rattay, Frank; Minassian, Karen

2014-01-01

Stimulation of different spinal cord segments in humans is a widely developed clinical practice for modification of pain, altered sensation and movement. The human lumbar cord has become a target for modification of motor control by epidural and more recently by transcutaneous spinal cord stimulation. Posterior columns of the lumbar spinal cord represent a vertical system of axons and when activated can add other inputs to the motor control of the spinal cord than stimulated posterior roots. We used a detailed three-dimensional volume conductor model of the torso and the McIntyre-Richard-Grill axon model to calculate the thresholds of axons within the posterior columns in response to transcutaneous lumbar spinal cord stimulation. Superficially located large diameter posterior column fibers with multiple collaterals have a threshold of 45.4 V, three times higher than posterior root fibers (14.1 V). With the stimulation strength needed to activate posterior column axons, posterior root fibers of large and small diameters as well as anterior root fibers are co-activated. The reported results inform on these threshold differences, when stimulation is applied to the posterior structures of the lumbar cord at intensities above the threshold of large-diameter posterior root fibers. PMID:21401670

Involvement of peripheral and spinal tumor necrosis factor α in spinal cord hyperexcitability during knee joint inflammation in rats.

PubMed

König, Christian; Zharsky, Maxim; Möller, Christian; Schaible, Hans-Georg; Ebersberger, Andrea

2014-03-01

Tumor necrosis factor α (TNFα) is produced not only in peripheral tissues, but also in the spinal cord. The purpose of this study was to address the potential of peripheral and spinal TNFα to induce and maintain spinal hyperexcitability, which is a hallmark of pain states in the joints during rheumatoid arthritis and osteoarthritis. In vivo recordings of the responses of spinal cord neurons to nociceptive knee input under normal conditions and in the presence of experimental knee joint inflammation were obtained in anesthetized rats. TNFα, etanercept, or antibodies to TNF receptors were applied to either the knee joint or the spinal cord surface. Injection of TNFα into the knee joint cavity increased the responses of spinal cord neurons to mechanical joint stimulation, and injection of etanercept into the knee joint reduced the inflammation-evoked spinal activity. These spinal effects closely mirrored the induction and reduction of peripheral sensitization. Responses to joint stimulation were also enhanced by spinal application of TNFα, and spinal application of either etanercept or anti-TNF receptor type I significantly attenuated the generation of inflammation-evoked spinal hyperexcitability, which is characterized by widespread pain sensitization beyond the inflamed joint. Spinally applied etanercept did not reduce established hyperexcitability in the acute kaolin/carrageenan model. In antigen-induced arthritis, etanercept decreased spinal responses on day 1, but not on day 3. While peripheral TNFα increases spinal responses to joint stimulation, spinal TNFα supports the generation of the full pattern of spinal hyperexcitability. However, established spinal hyperexcitability may be maintained by downstream mechanisms that are independent of spinal TNFα. Copyright © 2014 by the American College of Rheumatology.

Focal thoracolumbar spinal cord lymphosarcoma in a ferret (Mustela putorius furo)

PubMed Central

Ingrao, Joelle C.; Eshar, David; Vince, Andrew; Lee-Chow, Bridget; Nykamp, Stephanie; DeLay, Josepha; Smith, Dale

2014-01-01

A 6-year-old, castrated male domestic ferret (Mustela putorius furo) was euthanized following progressive hind limb paresis and atonia of the bladder of 1-year duration. Neurological evaluation localized the lesion to the thoracolumbar spinal region, and magnetic resonance imaging showed a focal intramedullary spinal cord lesion. Histopathology revealed an extensive, unencapsulated, poorly demarcated mass within the thoracolumbar spinal cord, diagnosed as lymphosarcoma. PMID:24982519

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

PubMed Central

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

2014-01-01

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

Neuroprosthetics and Solutions for Spinal Cord Dysfunctions

DTIC Science & Technology

2012-08-01

SSNI. 0 1 2 3 4 5 60 0.2 0.4 0.6 0.8 1 Stimulus amplitude (µA) P( rec rui tin g a t le ast n ne uro ns ) P(n=0|I) P(n=1|I) P(n=2|I) P(n=3|I) P(n=4|I...Annual Fall Meeting. Los Angeles, CA: 2007. 15 Bourbeau DJ, Hokanson J, Weber DJ. (2008). A computational model for examining activation of peripheral

A quadriplegic patient's cholescintigraphic findings: delayed gallbladder visualization and common bile duct dilation.

PubMed Central

Shih, W. J.; Magoun, S.; Lu, G.

1996-01-01

A Tc-99m DISIDA cholescintigraphic study of a 37-year-old patient with a 20-year history of quadriplegia demonstrated dilation of the common bile duct and delayed gallbladder visualization. A concurrent sonographic study showed an enlarged gallbladder with stones and dilation of the common bile duct. These findings were proved by autopsy. Quadriplegia secondary to a high level of spinal cord injury may result in gallbladder dysfunction. Images Figure PMID:8776068

[Oswald Schwarz: a pioneer in psychosomatic urology and sexual medicine].

PubMed

Berberich, H J; Schultheiss, D; Kieser, B

2015-01-01

Oswald Schwarz, a urologist from Vienna, was a scholar of Anton Ritter von Frisch and Hans Rubritius. As a physician during World War I, he was confronted with numerous bullet wounds to the spinal cord. In 1919, he completed his professorial thesis"Bladder dysfunction as a result of bullet wounds to the spinal cord". Oswald Schwarz was known as a committed surgeon. As an urologist he also treated patients with sexual dysfunction. Besides his practical and scientific urology-related work, he was also interested in psychology and philosophy. He held lectures on both subjects earning himself the nickname, the Urosoph. In the 1920s, Oswald Schwarz belonged to the inner circle of Alfred Adler, the founder of Individual Psychology, and was editor of the first psychosomatic textbook published in German, "Psychological origin and psychotherapy of physical symptoms" (1925). In addition, Schwarz wrote numerous articles and several books on sexual medicine. He also made many valuable contributions to the development of medical anthropology. Altogether, his work includes over 130 publications. Faced with the rise of fascism and National Socialism in Europe, Oswald Schwarz, who was of Jewish origin, emigrated to England in 1934. There he died in 1949. Unfortunately his scientific work has largely been forgotten. The aim of the following article is to remind us of his important contributions to the field.

Sexual concerns after Spinal Cord Injury: An update on management.

PubMed

Alexander, Marcalee Sipski; Aisen, Carrie Mlynarczyk; Alexander, Sterling Morrison; Aisen, Mindy Lipson

2017-01-01

Spinal Cord Injury (SCI) causes neurological impairment with resultant neurogenic sexual dysfunction which can compound preexisting psychological and medical sexual concerns. Understanding these concerns is important in managing the lifelong needs of persons with SCIs. To provide an overview of the impact of SCI on sexuality along with a framework for treatment of sexual concerns. To briefly review male infertility and its treatments and pregnancy in females after SCI. Interdisciplinary literature review and synthesis of information. The average age at SCI is increased, thus persons with SCIs may have preexisting sexual concerns. Sexual activity and satisfaction are decreased after SCI. Psychogenic sexual arousal is related to remaining sensation in the T11-L2 dermatomes. Orgasm occurs in approximately 50% of persons with SCIs with all injuries except subjects with complete lower motor neuron (LMN) injuries affecting the lowest sacral segments A structured approach to treatment including assessing preinjury function, determining the impact of injury, education, assessing and treating iatrogenic sexual dysfunction and treatment of concomitant problems is recommended. Basic and advanced methods to improve sexual arousal and orgasm are discussed and treatment of anejaculation and issues associated with pregnancy and SCI are reviewed. Sexual satisfaction is impaired after SCI; however, education and new therapies can improve responsiveness. Future research is warranted to improve sexual function and fertility potential in persons with SCIs.

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

PubMed

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

2008-03-01

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

Reduction of microhemorrhages in the spinal cord of symptomatic ALS mice after intravenous human bone marrow stem cell transplantation accompanies repair of the blood-spinal cord barrier.

PubMed

Eve, David J; Steiner, George; Mahendrasah, Ajay; Sanberg, Paul R; Kurien, Crupa; Thomson, Avery; Borlongan, Cesar V; Garbuzova-Davis, Svitlana

2018-02-13

Blood-spinal cord barrier (BSCB) alterations, including capillary rupture, have been demonstrated in animal models of amyotrophic lateral sclerosis (ALS) and ALS patients. To date, treatment to restore BSCB in ALS is underexplored. Here, we evaluated whether intravenous transplantation of human bone marrow CD34 + (hBM34 + ) cells into symptomatic ALS mice leads to restoration of capillary integrity in the spinal cord as determined by detection of microhemorrhages. Three different doses of hBM34 + cells (5 × 10 4 , 5 × 10 5 or 1 × 10 6 ) or media were intravenously injected into symptomatic G93A SOD1 mice at 13 weeks of age. Microhemorrhages were determined in the cervical and lumbar spinal cords of mice at 4 weeks post-treatment, as revealed by Perls' Prussian blue staining for ferric iron. Numerous microhemorrhages were observed in the gray and white matter of the spinal cords in media-treated mice, with a greater number of capillary ruptures within the ventral horn of both segments. In cell-treated mice, microhemorrhage numbers in the cervical and lumbar spinal cords were inversely related to administered cell doses. In particular, the pervasive microvascular ruptures determined in the spinal cords in late symptomatic ALS mice were significantly decreased by the highest cell dose, suggestive of BSCB repair by grafted hBM34 + cells. The study results provide translational outcomes supporting transplantation of hBM34 + cells at an optimal dose as a potential therapeutic strategy for BSCB repair in ALS patients.

"My body was my temple": a narrative revealing body image experiences following treatment of a spinal cord injury.

PubMed

Bailey, K Alysse; Gammage, Kimberley L; van Ingen, Cathy; Ditor, David S

2017-09-01

This narrative explores the lived experience of a young woman, Rebecca, and her transitioned body image after sustaining and being treated for a spinal cord injury. Data were collected from a single semi-structured in-depth interview. Rebecca disclosed her transitioned body image experiences after sustaining a spinal cord injury and being treated by medical staff immediately following her injury. Before her injury, she described a holistic body experience and named this experience her "temple". During intensive care in the hospital, she explained her body was treated as an object. The disconnected treatment of her body led to a loss of the private self, as she described her sacred body being stripped away - her "temple" lost and in ruins. Body image may be an overlooked component of health following a spinal cord injury. This narrative emphasizes the importance of unveiling body image experiences after the treatment of a spinal cord injury to medical professionals. Lessons of the importance of considering the transitioned body experiences after a spinal cord injury may help prevent body-related depression and other subsequent health impacts. Recommendations for best practice are provided. Implications for Rehabilitation    Spinal Cord Injury   • A spinal cord injury may drastically change a person's body image, thereby significantly impacting psychological health   • More effective screening for body image within the medical/rehabilitation context is needed to help practitioners recognize distress   • Practitioners should be prepared to refer clients to distress hotlines they may need once released from treatment.

Trident sign trumps Aquaporin-4-IgG ELISA in diagnostic value in a case of longitudinally extensive transverse myelitis.

PubMed

Jolliffe, Evan A; Keegan, B Mark; Flanagan, Eoin P

2018-04-21

Longitudinally-extensive T2-hyperintense spinal cord lesions (≥3 vertebral segments) are associated with neuromyelitis optical spectrum disorder but occur with other disorders including spinal cord sarcoidosis. When linear dorsal subpial enhancement is accompanied by central cord/canal enhancement the axial post-gadolinium sequences may reveal a "trident" pattern that has previously been shown to be strongly suggestive of spinal cord sarcoidosis. We report a case in which the patient was initially diagnosed with neuromyelitis optical spectrum disorder, but where the "trident" sign ultimately led to the correct diagnosis of spinal cord sarcoidosis. Copyright © 2018. Published by Elsevier B.V.

Attachment Style, Social Support, and Coping as Psychosocial Correlates of Happiness in Persons with Spinal Cord Injuries

ERIC Educational Resources Information Center

Wilson, Lisa; Catalano, Denise; Sung, Connie; Phillips, Brian; Chou, Chih-Chin; Chan, Jacob Yui Chung; Chan, Fong

2013-01-01

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…

[Rehabilitation programme using neuromuscular electrical stimulation in spinal cord: epidemiological aspects].

PubMed

Bittar, Cíntia Kelly; Cliquet, Alberto

2011-01-01

To assess epidemiological profile of spinal cord injury outpatients which have been participating of rehabilitation programme using neuromuscular electrical stimulation, in order to implement campaigns for preventing spinal cord trauma. From January to April 2009, 30 patients at the spinal cord injury ambulatory clinic at Hospital das Clínicas of Unicamp were analysed by some epidemiologic characteristics: age, profession, type and level of their paralysis, origin and time of injury. All patients had complete spinal cord injury (ASIA); 24 patients were men and six were women, the mean age was 34.6 years (range, 10-64 years), two patients were children. Twenty-one patients were paraplegic and nine were tetraplegic; causes included automobile accident (12), run over (three), diving (four), bicycle accident (one), motorcycle accident (three), gunshot wound (six), thoracic tuberculosis (one), and lumbar surgery (one). The mean lesion time was 8.2 years (range, 1-15 years). Two patients were retired. The results suggested that spinal cord injury affects mainly young active men. It is necessary to develop incisive actions to prevent accidents, specially directed to traffic security.

'Full dose' reirradiation of human cervical spinal cord.

PubMed

Ryu, S; Gorty, S; Kazee, A M; Bogart, J; Hahn, S S; Dalal, P S; Chung, C T; Sagerman, R H

2000-02-01

With the progress of modern multimodality cancer treatment, retreatment of late recurrences or second tumors became more commonly encountered in management of patients with cancer. Spinal cord retreatment with radiation is a common problem in this regard. Because radiation myelopathy may result in functional deficits, many oncologists are concerned about radiation-induced myelopathy when retreating tumors located within or immediately adjacent to the previous radiation portal. The treatment decision is complicated because it requires a pertinent assessment of prognostic factors with and without reirradiation, radiobiologic estimation of recovery of occult spinal cord damage from the previous treatment, as well as interactions because of multimodality treatment. Recent studies regarding reirradiation of spinal cord in animals using limb paralysis as an endpoint have shown substantial and almost complete recovery of spinal cord injury after a sufficient time after the initial radiotherapy. We report a case of "full" dose reirradiation of the entire cervical spinal cord in a patient who has not developed clinically detectable radiation-induced myelopathy on long-term follow-up of 17 years after the first radiotherapy and 5 years after the second radiotherapy.

Extracellular matrix-derived hydrogels for dental stem cell delivery.

PubMed

Viswanath, Aiswarya; Vanacker, Julie; Germain, Loïc; Leprince, Julian G; Diogenes, Anibal; Shakesheff, Kevin M; White, Lisa J; des Rieux, Anne

2017-01-01

Decellularized mammalian extracellular matrices (ECM) have been widely accepted as an ideal substrate for repair and remodelling of numerous tissues in clinical and pre-clinical studies. Recent studies have demonstrated the ability of ECM scaffolds derived from site-specific homologous tissues to direct cell differentiation. The present study investigated the suitability of hydrogels derived from different source tissues: bone, spinal cord and dentine, as suitable carriers to deliver human apical papilla derived mesenchymal stem cells (SCAP) for spinal cord regeneration. Bone, spinal cord, and dentine ECM hydrogels exhibited distinct structural, mechanical, and biological characteristics. All three hydrogels supported SCAP viability and proliferation. However, only spinal cord and bone derived hydrogels promoted the expression of neural lineage markers. The specific environment of ECM scaffolds significantly affected the differentiation of SCAP to a neural lineage, with stronger responses observed with spinal cord ECM hydrogels, suggesting that site-specific tissues are more likely to facilitate optimal stem cell behavior for constructive spinal cord regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 319-328, 2017. © 2016 Wiley Periodicals, Inc.

The mechanism of Naringin-enhanced remyelination after spinal cord injury

PubMed Central

Rong, Wei; Pan, Yong-wei; Cai, Xu; Song, Fei; Zhao, Zhe; Xiao, Song-hua; Zhang, Cheng

2017-01-01

Our previous study revealed that intragastric administration of naringin improved remyelination in rats with spinal cord injury and promoted the recovery of neurological function of the injured spinal cord. This study sought to reveal the mechanisms by which naringin improves oligodendrocyte precursor cell differentiation and maturation, and promotes remyelination. Spinal cord injury was induced in rats by the weight-drop method. Naringin was intragastrically administered daily (20, 40 mg/kg) for 4 weeks after spinal cord injury induction. Behavioral assessment, histopathological staining, immunofluorescence spectroscopy, ultrastructural analysis and biochemical assays were employed. Naringin treatment remarkably mitigated demyelination in the white matter, increased the quality of myelinated nerve fibers and myelin sheath thickness, promoted oligodendrocyte precursor cell differentiation by upregulating the expression of NKx2.2 and 2′3′-cyclic nucleotide 3′-phosphodiesterase, and inhibited β-catenin expression and glycogen synthase kinase-3β (GSK-3β) phosphorylation. These findings indicate that naringin treatment regulates oligodendrocyte precursor cell differentiation and promotes remyelination after spinal cord injury through the β-catenin/GSK-3β signaling pathway. PMID:28469664

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

PubMed

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

2013-03-01

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

Distribution of syringomyelia along the entire spinal cord in clinically affected Cavalier King Charles Spaniels.

PubMed

Loderstedt, Shenja; Benigni, Livia; Chandler, Kate; Cardwell, Jacqueline M; Rusbridge, Clare; Lamb, Christopher R; Volk, Holger A

2011-12-01

Chiari-like malformation (CM) and syringomyelia (SM) is an important disease complex in the Cavalier King Charles Spaniel (CKCS) but data about the anatomical distribution of SM along the spinal cord are lacking in veterinary medicine. The objective of this study was to define the anatomic distribution of SM in CKCS clinically affected by CM/SM. Magnetic resonance imaging (MRI) of the brain and the entire spinal cord of 49 dogs was performed and different morphological parameters compared. Syrinx formation was present in the C1-C4 region and in other parts of the spinal cord. The maximal dorsoventral syrinx size can occur in any region of the spinal cord and the total syrinx size was positively correlated with age. Seventy-six per cent of CKCS with a cranial cervical syrinx also have a syrinx affecting more caudal spinal cord regions. MRI restricted to the cervical region may underestimate the extent of SM and the severity of the disease process in the majority of dogs. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-01-01

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

The retrograde delivery of adenovirus vector carrying the gene for brain-derived neurotrophic factor protects neurons and oligodendrocytes from apoptosis in the chronically compressed spinal cord of twy/twy mice.

PubMed

Uchida, Kenzo; Nakajima, Hideaki; Hirai, Takayuki; Yayama, Takafumi; Chen, Kebing; Guerrero, Alexander Rodriguez; Johnson, William Eustace; Baba, Hisatoshi

2012-12-15

The twy/twy mouse undergoes spontaneous chronic mechanical compression of the spinal cord; this in vivo model system was used to examine the effects of retrograde adenovirus (adenoviral vector [AdV])-mediated brain-derived neurotrophic factor (BDNF) gene delivery to spinal neural cells. To investigate the targeting and potential neuroprotective effect of retrograde AdV-mediated BDNF gene transfection in the chronically compressed spinal cord in terms of prevention of apoptosis of neurons and oligodendrocytes. Several studies have investigated the neuroprotective effects of neurotrophins, including BDNF, in spinal cord injury. However, no report has described the effects of retrograde neurotrophic factor gene delivery in compressed spinal cords, including gene targeting and the potential to prevent neural cell apoptosis. AdV-BDNF or AdV-LacZ (as a control gene) was injected into the bilateral sternomastoid muscles of 18-week old twy/twy mice for retrograde gene delivery via the spinal accessory motor neurons. Heterozygous Institute of Cancer Research mice (+/twy), which do not undergo spontaneous spinal compression, were used as a control for the effects of such compression on gene delivery. The localization and cell specificity of β-galactosidase expression (produced by LacZ gene transfection) and BDNF expression in the spinal cord were examined by coimmunofluorescence staining for neural cell markers (NeuN, neurons; reactive immunology protein, oligodendrocytes; glial fibrillary acidic protein, astrocytes; OX-42, microglia) 4 weeks after gene injection. The possible neuroprotection afforded by retrograde AdV-BDNF gene delivery versus AdV-LacZ-transfected control mice was assessed by scoring the prevalence of apoptotic cells (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells) and immunoreactivity to active caspases -3, -8, and -9, p75, neurofilament 200 kD (NF), and for the oligodendroglial progenitor marker, NG2. RESULTS.: Four weeks after injection, the retrograde delivery of the LacZ marker gene was identified in cervical spinal neurons and some glial cells, including oligodendrocytes in the white matter of the spinal cord, in both the twy/twy mouse and the heterozygous Institute of Cancer Research mouse (+/twy). In the compressed spinal cord of twy/twy mouse, AdV-BDNF gene transfection resulted in a significant decrease in the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells present in the spinal cord and a downregulation in the caspase apoptotic pathway compared with AdV-LacZ (control) gene transfection. There was a marked and significant increase in the areas of the spinal cord of AdV-BDNF-injected mice that were NF- and NG2-immunopositive compared with AdV-LacZ-injected mice, indicating the increased presence of neurons and oligodendrocytes in response to BDNF transfection. Our results demonstrate that targeted retrograde BDNF gene delivery suppresses apoptosis in neurons and oligodendrocytes in the chronically compressed spinal cord of twy/twy mouse. Further work is required to establish whether this method of gene delivery may provide neuroprotective effects in other situations of compressive spinal cord injury.

Targeting Lumbar Spinal Neural Circuitry by Epidural Stimulation to Restore Motor Function After Spinal Cord Injury.

PubMed

Minassian, Karen; McKay, W Barry; Binder, Heinrich; Hofstoetter, Ursula S

2016-04-01

Epidural spinal cord stimulation has a long history of application for improving motor control in spinal cord injury. This review focuses on its resurgence following the progress made in understanding the underlying neurophysiological mechanisms and on recent reports of its augmentative effects upon otherwise subfunctional volitional motor control. Early work revealed that the spinal circuitry involved in lower-limb motor control can be accessed by stimulating through electrodes placed epidurally over the posterior aspect of the lumbar spinal cord below a paralyzing injury. Current understanding is that such stimulation activates large-to-medium-diameter sensory fibers within the posterior roots. Those fibers then trans-synaptically activate various spinal reflex circuits and plurisegmentally organized interneuronal networks that control more complex contraction and relaxation patterns involving multiple muscles. The induced change in responsiveness of this spinal motor circuitry to any residual supraspinal input via clinically silent translesional neural connections that have survived the injury may be a likely explanation for rudimentary volitional control enabled by epidural stimulation in otherwise paralyzed muscles. Technological developments that allow dynamic control of stimulation parameters and the potential for activity-dependent beneficial plasticity may further unveil the remarkable capacity of spinal motor processing that remains even after severe spinal cord injuries.

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

PubMed

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

2001-06-22

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

[Current status of neurostimulation and neuromodulation for vesicourethral dysfunction].

PubMed

González-Chamorro, F; Verdú Tartajo, F; Hernández Fernández, C

1997-01-01

To describe the current indications, techniques and results of sacral root stimulation in patients with spinal cord lesions as a treatment for patients with high pressure bladders and/or urinary incontinence despite conservative management, as well as sacral root neuromodulation with permanent stimulators for complex bladder dysfunction: vesical instability, sensory urgency, chronic pelvic pain and chronic voiding dysfunction. The literature is reviewed, both techniques are described and the results of the most significant series are discussed, with special reference to the first groups that utilized these techniques. There is ample experience in the application of sacral root electrical stimulation. The reported results are comparable with those achieved by other treatments, such as augmentation cystoplasty. Neurostimulation and neuromodulation techniques are simple, the complications are minimal and they do not prelude the use of other therapies.

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

PubMed

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

2012-12-01

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

Age, gender and normalization covariates for spinal cord gray matter and total cross-sectional areas at cervical and thoracic levels: A 2D phase sensitive inversion recovery imaging study.

PubMed

Papinutto, Nico; Schlaeger, Regina; Panara, Valentina; Zhu, Alyssa H; Caverzasi, Eduardo; Stern, William A; Hauser, Stephen L; Henry, Roland G

2015-01-01

The source of inter-subject variability and the influence of age and gender on morphometric characteristics of the spinal cord, such as the total cross-sectional area (TCA), the gray matter (GM) and white matter (WM) areas, currently remain under investigation. Understanding the effect of covariates such as age, gender, brain volumes, and skull- and vertebra-derived metrics on cervical and thoracic spinal cord TCA and GM areas in healthy subjects would be fundamental for exploring compartment specific changes in neurological diseases affecting the spinal cord. Using Magnetic Resonance Imaging at 3T we investigated 32 healthy subjects using a 2D phase sensitive inversion recovery sequence and we measured TCA, GM and WM areas at 4 cervical and thoracic levels of the spinal cord. We assessed age and gender relationships of cord measures and explored associations between cord measures and a) brain volumes and b) skull- and vertebra-derived metrics. Age and gender had a significant effect on TCA, WM and GM areas (with women and elderly having smaller values than men and younger people respectively), but not on the GM area/TCA ratio. The total intracranial volume and C3 vertebra dimensions showed the highest correlations with cord measures. When used in multi-regression models, they reduced cord areas group variability by approximately a third. Age and gender influences on cord measures and normalization strategies here presented might be of use in the study of compartment specific changes in various neurological diseases affecting the spinal cord.

The pathway of subarachnoid CSF moving into the spinal parenchyma and the role of astrocytic aquaporin-4 in this process.

PubMed

Wei, Fang; Zhang, Cui; Xue, Rong; Shan, Lidong; Gong, Shan; Wang, Guoqing; Tao, Jin; Xu, Guangyin; Zhang, Guoxing; Wang, Linhui

2017-08-01

It has been proved that cerebrospinal fluid (CSF) in the subarachnoid space could reenter the brain parenchyma via the perivascular space. The present study was designed to explore the pathway of subarachnoid CSF flux into the spinal cord and the potential role of aquaporin-4 (AQP4) in this process. Fluorescently tagged cadaverine, for the first time, was used to study CSF movement in mice. Following intracisternal infusion of CSF tracers, the cervical spinal cord was sliced and prepared for fluorescence imaging. Some sections were subject with immunostaining in order to observe tracer distribution and AQP4 expression. Fluorescently tagged cadaverine rapidly entered the spinal cord. Tracer influx into the spinal parenchyma was time dependent. At 10min post-infusion, cadaverine was largely distributed in the superficial tissue adjacent to the pial surface. At 70min post-infusion, cadaverine was distributed in the whole cord and especially concentrated in the gray matter. Furthermore, fluorescent tracer could enter the spinal parenchyma either along the perivascular space or across the pial surface. AQP4 was observed highly expressed in the astrocytic endfeet surrounding blood vessels and the pial surface. Blocking AQP4 by its specific inhibitor TGN-020 strikingly reduced the inflow of CSF tracers into the spinal cord. Subarachnoid CSF could flow into the spinal cord along the perivascular space or across the pial surface, in which AQP4 is involved. Our observation provides a basis for the study on CSF movement in the spinal cord when some neurological diseases occur. Copyright © 2017 Elsevier Inc. All rights reserved.

Different patterns of longitudinal brain and spinal cord changes and their associations with disability progression in NMO and MS.

PubMed

Liu, Yaou; Duan, Yunyun; Huang, Jing; Ren, Zhuoqiong; Liu, Zheng; Dong, Huiqing; Weiler, Florian; Hahn, Horst K; Shi, Fu-Dong; Butzkueven, Helmut; Barkhof, Frederik; Li, Kuncheng

2018-01-01

To investigate the longitudinal spinal cord and brain changes in neuromyelitis optica (NMO) and multiple sclerosis (MS) and their associations with disability progression. We recruited 28 NMO, 22 MS, and 20 healthy controls (HC), who underwent both spinal cord and brain MRI at baseline. Twenty-five NMO and 20 MS completed 1-year follow-up. Baseline spinal cord and brain lesion loads, mean upper cervical cord area (MUCCA), brain, and thalamus volume and their changes during a 1-year follow-up were measured and compared between groups. All the measurements were also compared between progressive and non-progressive groups in NMO and MS. MUCCA decreased significantly during the 1-year follow-up in NMO not in MS. Percentage brain volume changes (PBVC) and thalamus volume changes in MS were significantly higher than NMO. MUCCA changes were significantly different between progressive and non-progressive groups in NMO, while baseline brain lesion volume and PBVC were associated with disability progression in MS. MUCCA changes during 1-year follow-up showed association with clinical disability in NMO. Spinal cord atrophy changes were associated with disability progression in NMO, while baseline brain lesion load and whole brain atrophy changes were related to disability progression in MS. • Spinal cord atrophy progression was observed in NMO. • Spinal cord atrophy changes were associated with disability progression in NMO. • Brain lesion and atrophy were related to disability progression in MS.

The changing nature of admissions to a spinal cord injury center: violence on the rise.

PubMed

Farmer, J C; Vaccaro, A R; Balderston, R A; Albert, T J; Cotler, J

1998-10-01

The purpose of this study was to analyze changing etiologies for admission to a spinal cord injury center. This study was designed to retrospectively analyze the etiology of admissions to a spinal cord injury center during a 15-year period, specifically gunshot versus nongunshot wound injuries. Gunshot wounds are a well-recognized cause of spinal cord injury. In some centers, up to 52% of admissions are due to this, and these trends are believed to be increasing. All patients with spinal cord injury admitted to our center between 1979 and 1993 were analyzed. Frequencies of specific etiologies were determined and then comparisons were made between gunshot wound and nongunshot wound groups. Factors analyzed included age, male/female ratio, ethnic make-up, marital status, employment status, level of injury, and neurologic status. One thousand eight hundred seventeen patients were included. Overall, gunshot wound spinal cord injuries compromised 16.9% of injuries. A clear trend of increasing numbers of admissions was seen between 1984 and 1993 because of this. Gunshot wounds and nongunshot wounds differed dramatically in terms of age, ethnic make-up, marital status, employment status, and neurologic status. Cost attributed to treating gunshot wound injuries at our center for 1993 was 5.4 million dollars. Gunshot wounds as a cause of spinal cord injury are increasing at an alarming rate. The demographics of the gunshot wounds and nongunshot wound spine cord injuries differ significantly.

A dual physiological character for sexual function: libido and sexual pheromones.

PubMed

Motofei, Ion G

2009-12-01

Human sexual response is a complex function involving many cerebral, spinal and peripheral aspects; the last are relatively known and benefit from good pharmacological control, as in the case of erectile dysfunction. Spinal cord sexual reflexes also have a good theoretical and experimental description. There is minimal understanding of the cerebral sexual processes (libido, sexual arousal, orgasm). The initial perspective was that the cerebral areas implied in sexuality exert descending stimulatory and inhibitory influences on spinal cord sexual centres/reflexes. This was a wrong supposition, which inhibited progress in this subject, with a considerable impact on a subject's individual and social life. A new approach to sexual function arises from the idea that simple neurological structures can support only simple functions, while a more complex function requires correspondingly complex anatomical structures. For this reason the spinal cord would not be able to realise the integration of multiple (spinal and psychosensorial) stimuli into a unique and coherent ejaculation response. Consequently, all mechanisms implied in human sexuality would be cerebral processes, ejaculation reflexes ascending in evolution to the cerebral level. This new evolutionary concept was developed after 2001 in five distinct articles on the cerebral duality of sexual arousal, sexual hormones, ejaculation and serotonergic receptors. During this period other published results suggested a possible cerebral duality for sexual pheromones and libido in humans. All these dual physiological aspects are integrated in this review into one neurophysiological model, thus trying to further develop the new concepts of sexual function and perhaps relational behaviour. In conclusion, ejaculation is a dual cerebral process with arousal sensation (hormonally modulated) and libido perception (pheromonally modulated) as the afferent part. Two neurophysiological axes could exist in both men and women. In this assumption the mechanisms for libido and sexual arousal are not the only ones invoked, their correlations and implications are also suggested, perhaps critical aspects for further developments in the field.

The experience of attempting to return to work following spinal cord injury: a systematic review of the qualitative literature.

PubMed

Hilton, Gillean; Unsworth, Carolyn; Murphy, Gregory

2018-07-01

This review sought to answer the question "What are the barriers and facilitators influencing people's experience of return to work following spinal cord injury?" Studies that met the selection criteria were identified, presented and critically appraised using National Institute for Health and Care Excellence guidelines. Thematic synthesis was completed with studies possessing strong methodological rigor. Synthesis and interpretation involved three stages; coding of primary data; development of descriptive themes reflective of the primary data; and establishment of analytical themes to answer the review question. Data from nine papers were included in the thematic synthesis. Several descriptive themes and three analytical themes were drawn from the data to answer the research question. Analytical themes included: a matrix of personal and environmental factors exists requiring complex navigation in order to create possibilities and opportunities for postinjury employment; the process of seeking or gaining employment shares a reciprocal relationship with the temporal nature of adjustment to spinal cord injury; and there is an intrinsic need for occupational engagement through paid employment. Returning to or gaining employment after spinal cord injury is a fundamentally difficult experience for people. Multiple strategies are required to support the navigation of the process. There is, however, a need in people with spinal cord injury, to be a worker, and with that comes the inherent benefits of being employed. Implications for rehabilitation Returning to work should be a significant focus of spinal cord injury rehabilitation. Employment is both possible and health promoting following spinal cord injury. Multiple strategies are required to support people to navigate the return to work process. It is important to be cognizant of the individual motivations for being a worker and the complexity of the adjustment process. Spinal cord injury centers can provide a consistent and supportive framework and culture of positivity about employment after spinal cord injury.

Novel aspects of spinal cord evoked potentials (SCEPs) in the evaluation of dorso-ventral and lateral mechanical impacts on the spinal cord

NASA Astrophysics Data System (ADS)

Rad, Iman; Kouhzaei, Sogolie; Mobasheri, Hamid; Saberi, Hooshang

2015-02-01

Objectives. The aim of the current study was to mimic mechanical impacts on the spinal cord by manifesting the effects of dorsoventral (DVMP) and lateral (LMP) mechanical pressure on neural activity to address points to be considered during surgery for different purposes, including spinal cord decompression. Approaches. Spinal cords of anesthetized rats were compressed at T13. Different characteristics of axons, including vulnerability, excitability, and conduction velocity (CV), in response to promptness, severity, and duration of pressure were assessed by spinal cord evoked potentials (SCEPs). Real-time SCEPs recorded at L4-5 revealed N1, N2, and N3 peaks that were used to represent the activity of injured sensory afferents, interneurons, and MN fibers. The averaged SCEP recordings were fitted by trust-region algorithm to find the equivalent Gaussian and polynomial equations. Main results. The pyramidal and extrapyramidal pathways possessed CVs of 3-11 and 16-80 m s-1, respectively. DVMP decreased the excitability of myelinated neural fibers in antidromic and orthodromic pathways. The excitability of fibers in extrapyramidal and pyramidal pathways of lateral corticospinal (LCS) and anterior corticospinal (ACS) tracts decreased following LMP. A significant drop in the amplitude of N3 and its conduction velocity (CV) revealed higher susceptibility of less-myelinated fibers to both DVMP and LMP. The best parametric fitting model for triplet healthy spinal cord CAP was a six-term Gaussian equation (G6) that fell into a five-term equation (G5) at the complete compression stage. Significance. The spinal cord is more susceptible to dorsoventral than lateral mechanical pressures, and this should be considered in spinal cord operations. SCEPs have shown promising capabilities for evaluating the severity of SCI and thus can be applied for diagnostic or prognostic intraoperative monitoring (IOM).

Impact Depth and the Interaction with Impact Speed Affect the Severity of Contusion Spinal Cord Injury in Rats

PubMed Central

Lam, Cameron J.; Assinck, Peggy; Liu, Jie; Tetzlaff, Wolfram

2014-01-01

Abstract Spinal cord injury (SCI) biomechanics suggest that the mechanical factors of impact depth and speed affect the severity of contusion injury, but their interaction is not well understood. The primary aim of this work was to examine both the individual and combined effects of impact depth and speed in contusion SCI on the cervical spinal cord. Spinal cord contusions between C5 and C6 were produced in anesthetized rats at impact speeds of 8, 80, or 800 mm/s with displacements of 0.9 or 1.5 mm (n=8/group). After 7 days postinjury, rats were assessed for open-field behavior, euthanized, and spinal cords were harvested. Spinal cord tissue sections were stained for demyelination (myelin-based protein) and tissue sparing (Luxol fast blue). In parallel, a finite element model of rat spinal cord was used to examine the resulting maximum principal strain in the spinal cord during impact. Increasing impact depth from 0.9 to 1.5 mm reduced open-field scores (p<0.01) above 80 mm/s, reduced gray (GM) and white matter (WM) sparing (p<0.01), and increased the amount of demyelination (p<0.01). Increasing impact speed showed similar results at the 1.5-mm impact depth, but not the 0.9-mm impact depth. Linear correlation analysis with finite element analysis strain showed correlations (p<0.001) with nerve fiber damage in the ventral (R2=0.86) and lateral (R2=0.74) regions of the spinal cord and with WM (R2=0.90) and GM (R2=0.76) sparing. The results demonstrate that impact depth is more important in determining the severity of SCI and that threshold interactions exist between impact depth and speed. PMID:24945364

Regeneration of Xenopus laevis spinal cord requires Sox2/3 expressing cells

PubMed Central

Muñoz, Rosana; Edwards-Faret, Gabriela; Moreno, Mauricio; Zuñiga, Nikole; Cline, Hollis; Larraín, Juan

2016-01-01

Spinal cord regeneration is very inefficient in humans, causing paraplegia and quadriplegia. Studying model organisms that can regenerate the spinal cord in response to injury could be useful for understanding the cellular and molecular mechanisms that explain why this process fails in humans. Here, we use Xenopus laevis as a model organism to study spinal cord repair. Histological and functional analyses showed that larvae at pre-metamorphic stages restore anatomical continuity of the spinal cord and recover swimming after complete spinal cord transection. These regenerative capabilities decrease with onset of metamorphosis. The ability to study regenerative and non-regenerative stages in Xenopus laevis makes it a unique model system to study regeneration. We studied the response of Sox2/3 expressing cells to spinal cord injury and their function in the regenerative process. We found that cells expressing Sox2 and/or Sox3 are present in the ventricular zone of regenerative animals and decrease in non-regenerative froglets. Bromodeoxyuridine (BrdU) experiments and in vivo time-lapse imaging studies using green fluorescent protein (GFP) expression driven by the Sox3 promoter showed a rapid, transient and massive proliferation of Sox2/3+ cells in response to injury in the regenerative stages. The in vivo imaging also demonstrated that Sox2/3+ neural progenitor cells generate neurons in response to injury. In contrast, these cells showed a delayed and very limited response in non-regenerative froglets. Sox2 knockdown and overexpression of a dominant negative form of Sox2 disrupts locomotor and anatomical-histological recovery. We also found that neurogenesis markers increase in response to injury in regenerative but not in non-regenerative animals. We conclude that Sox2 is necessary for spinal cord regeneration and suggest a model whereby spinal cord injury activates proliferation of Sox2/3 expressing cells and their differentiation into neurons, a mechanism that is lost in non-regenerative froglets. PMID:25797152

Characteristics of AMPA receptor-mediated responses of cultured cortical and spinal cord neurones and their correlation to the expression of glutamate receptor subunits, GluR1-4

PubMed Central

Dai, Wei-Min; Egebjerg, Jan; Lambert, John D C

2001-01-01

Electrophysiological recordings have been used to characterize responses mediated by AMPA receptors expressed by cultured rat cortical and spinal cord neurones. The EC50 values for AMPA were 17 and 11 μM, respectively.Responses of cortical neurones to AMPA were inhibited competitively by NBQX (pKi=6.6). Lower concentrations of NBQX (⩽1 μM) also potentiated the plateau responses of spinal cord neurones to AMPA, which could be attributed to a depression of desensitization to AMPA.GYKI 52466 inhibited responses of spinal cord neurones to AMPA to about twice the extent of responses of cortical neurones.Blockade of AMPA receptor desensitization by cyclothiazide (CTZ) potentiated responses of spinal cord neurones (6.8 fold) significantly more than responses of cortical neurones (4.8 fold). Responses of cortical neurones to KA were potentiated 3.5 fold by CTZ, while responses of spinal cord neurones were unaffected.Ultra-fast applications of AMPA to outside-out patches showed responses of spinal cord neurones desensitized by 97.5% and exhibit marked inward rectification, whereas cortical neurones desensitized by 91% and exhibited slight outward rectification. The time constants of deactivation and desensitization were about twice as fast in spinal cord than cortical neurones.In cortical neurones, single-cell RT – PCR showed GluR2 and GluR1 accounted for 91% of all subunits and were expressed together in 67% of neurones, predominantly as the flip variants (78%). GluR2 was detected alone in 24% of neurones. GluR3 and GluR4 were present in only 14 and 29% of neurones, respectively. For spinal cord neurones, GluR4o was detected in 81% of neurones, whereas predominantly flop versions of GluR1, 2 and 3 were detected in 38, 13 and 13% of neurones, respectively. These expression patterns are related to the respective pharmacological and mechanistic properties. PMID:11309259

Fast and Accurate Semi-Automated Segmentation Method of Spinal Cord MR Images at 3T Applied to the Construction of a Cervical Spinal Cord Template

PubMed Central

El Mendili, Mohamed-Mounir; Trunet, Stéphanie; Pélégrini-Issac, Mélanie; Lehéricy, Stéphane; Pradat, Pierre-François; Benali, Habib

2015-01-01

Objective To design a fast and accurate semi-automated segmentation method for spinal cord 3T MR images and to construct a template of the cervical spinal cord. Materials and Methods A semi-automated double threshold-based method (DTbM) was proposed enabling both cross-sectional and volumetric measures from 3D T2-weighted turbo spin echo MR scans of the spinal cord at 3T. Eighty-two healthy subjects, 10 patients with amyotrophic lateral sclerosis, 10 with spinal muscular atrophy and 10 with spinal cord injuries were studied. DTbM was compared with active surface method (ASM), threshold-based method (TbM) and manual outlining (ground truth). Accuracy of segmentations was scored visually by a radiologist in cervical and thoracic cord regions. Accuracy was also quantified at the cervical and thoracic levels as well as at C2 vertebral level. To construct a cervical template from healthy subjects’ images (n=59), a standardization pipeline was designed leading to well-centered straight spinal cord images and accurate probability tissue map. Results Visual scoring showed better performance for DTbM than for ASM. Mean Dice similarity coefficient (DSC) was 95.71% for DTbM and 90.78% for ASM at the cervical level and 94.27% for DTbM and 89.93% for ASM at the thoracic level. Finally, at C2 vertebral level, mean DSC was 97.98% for DTbM compared with 98.02% for TbM and 96.76% for ASM. DTbM showed similar accuracy compared with TbM, but with the advantage of limited manual interaction. Conclusion A semi-automated segmentation method with limited manual intervention was introduced and validated on 3T images, enabling the construction of a cervical spinal cord template. PMID:25816143

Myxopapillary ependymoma as a cause of back pain in a young male – A case report

PubMed Central

Ngo, Trung P; Dufton, John; Stern, Paula J; Islam, Omar

2013-01-01

Objective: Primary spinal cord tumours are rare causes of low back pain but can be a significant cause of morbidity if undiagnosed and untreated. The following is a case of a young male patient presenting with low back pain and radicular symptoms caused by myxopapillary ependymoma. Clinical Features: A nineteen year old male presented to an orthopaedic surgeon with a long history of back pain. He was initially diagnosed with soft tissue injuries and discharged. He began to experience erectile and bowel dysfunction two years later and was re-referred to the orthopaedic surgeon by his family physician but was lost to follow-up. The patient did not present to the surgeon until two years after his symptom profile changed. At that point, MRI examinations revealed a large myxopapillary ependymoma extending from T12 to L4 that was confirmed by a pathologist. Intervention and Outcome: The tumour was surgically resected with subsequent adjuvant radiotherapy. After one year, the patient required continued catheterization and had poor anal tone. His back and leg complaints were almost normal. Follow-up MRI examinations revealed no disease progression or new spinal lesions at 4 years after the initial diagnosis. Conclusion: The clinical presentation of primary spinal cord tumours is non-specific and can easily be missed. In cases of chronic back pain, signs and symptoms should be regularly monitored for changes indicative of progressive neurological compromise such as sensory, motor and bowel/bladder dysfunction. If there is deterioration of clinical signs and symptoms, a spinal tumour should be considered in the list of differential diagnoses. Delayed diagnosis and treatment of these rare causes of back pain could lead to poor outcomes; therefore, a referral to a surgeon should be done immediately with proper follow up to ensure continuity of care. PMID:23754860

Making sense out of spinal cord somatosensory development

PubMed Central

Seal, Rebecca P.

2016-01-01

The spinal cord integrates and relays somatosensory input, leading to complex motor responses. Research over the past couple of decades has identified transcription factor networks that function during development to define and instruct the generation of diverse neuronal populations within the spinal cord. A number of studies have now started to connect these developmentally defined populations with their roles in somatosensory circuits. Here, we review our current understanding of how neuronal diversity in the dorsal spinal cord is generated and we discuss the logic underlying how these neurons form the basis of somatosensory circuits. PMID:27702783

Idiopathic thoracic transdural intravertebral spinal cord herniation

PubMed Central

Turel, Mazda K; Wewel, Joshua T; Kerolus, Mena G; O'Toole, John E

2017-01-01

Idiopathic spinal cord herniation is a rare and often missed cause of thoracic myelopathy. The clinical presentation and radiological appearance is inconsistent and commonly confused with a dorsal arachnoid cyst and often is a misdiagnosed entity. While ventral spinal cord herniation through a dural defect has been previously described, intravertebral herniation is a distinct entity and extremely rare. We present the case of a 70-year old man with idiopathic thoracic transdural intravertebral spinal cord herniation and discuss the clinico-radiological presentation, pathophysiology and operative management along with a review the literature of this unusual entity. PMID:29021685

Reduce, reuse, recycle - Developmental signals in spinal cord regeneration.

PubMed

Cardozo, Marcos Julian; Mysiak, Karolina S; Becker, Thomas; Becker, Catherina G

2017-12-01

Anamniotes, fishes and amphibians, have the capacity to regenerate spinal cord tissue after injury, generating new neurons that mature and integrate into the spinal circuitry. Elucidating the molecular signals that promote this regeneration is a fundamental question in regeneration research. Model systems, such as salamanders and larval and adult zebrafish are used to analyse successful regeneration. This shows that many developmental signals, such as Notch, Hedgehog (Hh), Bone Morphogenetic Protein (BMP), Wnt, Fibroblast Growth Factor (FGF), Retinoic Acid (RA) and neurotransmitters are redeployed during regeneration and activate resident spinal progenitor cells. Here we compare the roles of these signals in spinal cord development and regeneration of the much larger and fully patterned adult spinal cord. Understanding how developmental signalling systems are reactivated in successfully regenerating species may ultimately lead to ways to reactivate similar systems in mammalian progenitor cells, which do not show neurogenesis after spinal injury. Copyright © 2017. Published by Elsevier Inc.

SMN regulates axonal local translation via miR-183/mTOR pathway

PubMed Central

Kye, Min Jeong; Niederst, Emily D.; Wertz, Mary H.; Gonçalves, Inês do Carmo G.; Akten, Bikem; Dover, Katarzyna Z.; Peters, Miriam; Riessland, Markus; Neveu, Pierre; Wirth, Brunhilde; Kosik, Kenneth S.; Sardi, S. Pablo; Monani, Umrao R.; Passini, Marco A.; Sahin, Mustafa

2014-01-01

Reduced expression of SMN protein causes spinal muscular atrophy (SMA), a neurodegenerative disorder leading to motor neuron dysfunction and loss. However, the molecular mechanisms by which SMN regulates neuronal dysfunction are not fully understood. Here, we report that reduced SMN protein level alters miRNA expression and distribution in neurons. In particular, miR-183 levels are increased in neurites of SMN-deficient neurons. We demonstrate that miR-183 regulates translation of mTor via direct binding to its 3′ UTR. Interestingly, local axonal translation of mTor is reduced in SMN-deficient neurons, and this can be recovered by miR-183 inhibition. Finally, inhibition of miR-183 expression in the spinal cord of an SMA mouse model prolongs survival and improves motor function of Smn-mutant mice. Together, these observations suggest that axonal miRNAs and the mTOR pathway are previously unidentified molecular mechanisms contributing to SMA pathology. PMID:25055867

JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain.

PubMed

Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

2009-04-01

Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha (TNF-alpha) transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-alpha/JNK pathway. MCP-1 upregulation by TNF-alpha was dose dependently inhibited by the JNK inhibitors SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) and D-JNKI-1. Spinal injection of TNF-alpha produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Furthermore, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch-clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous EPSCs but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes after JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management.

Repair of spinal cord injury with neuronal relays: From fetal grafts to neural stem cells.

PubMed

Bonner, Joseph F; Steward, Oswald

2015-09-04

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. Copyright © 2015 Elsevier B.V. All rights reserved.

Resilience and the rehabilitation of adult spinal cord injury survivors: A qualitative systematic review.

PubMed

Kornhaber, Rachel; Mclean, Loyola; Betihavas, Vasiliki; Cleary, Michelle

2018-01-01

To synthesize the qualitative research evidence that explored how survivors of adult spinal cord injury experience and make sense of resilience. Spinal cord injury is often a sudden and unexpected life-changing event requiring complex and long-term rehabilitation. The development of resilience is essential in determining how spinal cord injury survivors negotiate this injury and rehabilitation. A qualitative systematic review and thematic synthesis of the research evidence. CINAHL, PubMed, Embase, Scopus and PsycINFO were searched, no restriction dates were used. Methodological quality was assessed using the Critical Appraisal Skills Programme checklist. Thematic synthesis focused on how survivors of adult spinal cord injury experience and make sense of resilience. Six qualitative research articles reported the experiences of 84 spinal cord injury survivors. Themes identified were: uncertainty and regaining independence; prior experiences of resilience; adopting resilient thinking; and strengthening resilience through supports. Recovery and rehabilitation following spinal cord survivors is influenced by the individual's capacity for resilience. Resilience may be influenced by previous life experiences and enhanced by supportive nursing staff encouraging self-efficacy. Survivors identified the need for active involvement in decision-making about their care to enable a sense of regaining control of their lives. This has the potential to have a significant impact on their self-efficacy and in turn health outcomes. © 2017 John Wiley & Sons Ltd.

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

PubMed

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

2015-02-01

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

Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia

NASA Technical Reports Server (NTRS)

Zeitzer, J. M.; Ayas, N. T.; Shea, S. A.; Brown, R.; Czeisler, C. A.

2000-01-01

The human circadian timing system regulates the temporal organization of several endocrine functions, including the production of melatonin (via a neural pathway that includes the spinal cord), TSH, and cortisol. In traumatic spinal cord injury, afferent and efferent circuits that influence the basal production of these hormones may be disrupted. We studied five subjects with chronic spinal cord injury (three tetraplegic and two paraplegic, all neurologically complete injuries) under stringent conditions in which the underlying circadian rhythmicity of these hormones could be examined. Melatonin production was absent in the three tetraplegic subjects with injury to their lower cervical spinal cord and was of normal amplitude and timing in the two paraplegic subjects with injury to their upper thoracic spinal cord. The amplitude and the timing of TSH and cortisol rhythms were robust in the paraplegics and in the tetraplegics. Our results indicate that neurologically complete cervical spinal injury results in the complete loss of pineal melatonin production and that neither the loss of melatonin nor the loss of spinal afferent information disrupts the rhythmicity of cortisol or TSH secretion.

Phantom sensations in people with complete spinal cord lesions: a grounded theory perspective.

PubMed

Drysdale, Daren G; Shem, Kazuko; Walbom, Agnes; Miner, Maureen D; Maclachlan, Malcolm

2009-01-01

Phantom sensations are somatic phenomena arising from denervated parts of the body. There is very little research, and much diagnostic confusion, regarding such experiences in people with spinal cord injuries. In the case of 'complete' spinal cord lesions, phantom experiences may challenge, and indeed, contradict, the understanding that both clinicians and patients have of such injuries. This paper seeks to provide a better understanding of such 'phantom' sensations in spinal cord injury. We used grounded theory methods to explore 'phantom' sensations as experienced by individuals with complete (ASIA A) spinal lesions. Eight people with complete lesions, who were selected through theoretical sampling, participated in a semi-structured interview. Emergent themes included injury context, sensations experienced, the meaning of sensations, body connectivity, attitude and communication about sensations. Our results provide an enhanced understanding of the embodied experience of phantom sensations, and important insights regarding self-construction and rehabilitative processes in people with spinal cord injury who experience such anomalous sensations.

[Attempts at management of experimental spinal cord hemisection by complete immobilization of the spine in dogs].

PubMed

Renard, C

1980-06-01

This animal experimentation shows the results of a method aiming at proving the possibilities of medullar reconstruction, if the medullar surfaces are in firm contact ant if medullar tension is neutralized. After hemitransection of the spinal cord, a total spinal immobilization in extension is obtained by using an original orthopaedic prosthesis. Thus, we operated on five dogs, one of which, the reference dog, underwent hemitransection of the spinal cord but no spine immobilization. From a clinical point of view, this dog developed a spastic crural monoplegia, whereas recuperation of motricity by the other dogs was surprising. Histological studies allowed us to observe a certain re-establishment of the spinal cord continuity, suggesting the beginning of an organization of a regeneration mechanism. These statements show the harmful influence of intra-medullar tension for spinal cord reconstruction. In practice, tractions on the spine must be abandoned for they increase the intramedullar tension very much and compromise any eventual "recuperation" after a medullar traumatism.

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

PubMed

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

2018-06-01

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

Contributions of identifiable neurons and neuron classes to lamprey vertebrate neurobiology.

PubMed

Buchanan, J T

2001-03-01

Among the advantages offered by the lamprey brainstem and spinal cord for studies of the structure and function of the nervous system is the unique identifiability of several pairs of reticulospinal neurons in the brainstem. These neurons have been exploited in investigations of the patterns of sensory input to these cells and the patterns of their outputs to spinal neurons, but no doubt these cells could be used much more effectively in exploring their roles in descending control of the spinal cord. The variability of cell positions of neurons in the spinal cord has precluded the recognition of unique spinal neurons. However, classes of nerve cells can be readily defined and characterized within the lamprey spinal cord and this has led to progress in understanding the cellular and synaptic mechanisms of locomotor activity. In addition, both the identifiable reticulospinal cells and the various spinal nerve cell classes and their known synaptic interactions have been used to demonstrate the degree and specificity of regeneration within the lamprey nervous system. The lack of uniquely identifiable cells within the lamprey spinal cord has hampered progress in these areas, especially in gaining a full understanding of the locomotor network and how neuromodulation of the network is accomplished.

Exercise recommendations for individuals with spinal cord injury.

PubMed

Jacobs, Patrick L; Nash, Mark S

2004-01-01

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 within the paralysed tissues. The recommendations for endurance and strength training in persons with SCI do not vary dramatically from the advice offered to the general population. Systems of functional electrical stimulation activate muscular contractions within the paralysed muscles of some persons with SCI. Coordinated patterns of stimulation allows purposeful exercise movements including recumbent cycling, rowing and upright ambulation. Exercise activity in persons with SCI is not without risks, with increased risks related to systemic dysfunction following the spinal injury. These individuals may exhibit an autonomic dysreflexia, significantly reduced bone density below the spinal lesion, joint contractures and/or thermal dysregulation. Persons with SCI can benefit greatly by participation in exercise activities, but those benefits can be enhanced and the relative risks may be reduced with accurate classification of the spinal injury.

Measurement Structure of the Trait Hope Scale in Persons with Spinal Cord Injury: A Confirmatory Factor Analysis

ERIC Educational Resources Information Center

Smedema, Susan Miller; Pfaller, Joseph; Moser, Erin; Tu, Wei-Mo; Chan, Fong

2013-01-01

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…

Religiosity and Spirituality among Persons with Spinal Cord Injury: Attitudes, Beliefs, and Practices

ERIC Educational Resources Information Center

Marini, Irmo; Glover-Graf, Noreen M.

2011-01-01

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…

Body composition of active persons with spinal cord injury and with poliomyelitis

USDA-ARS?s Scientific Manuscript database

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...

Ex Vivo Diffusion Tensor Imaging of Spinal Cord Injury in Rats of Varying Degrees of Severity

PubMed Central

Jirjis, Michael B.; Kurpad, Shekar N.

2013-01-01

Abstract The aim of this study was to characterize magnetic resonance diffusion tensor imaging (DTI) in proximal regions of the spinal cord following a thoracic spinal cord injury (SCI). Sprague–Dawley rats (n=40) were administered a control, mild, moderate, or severe contusion injury at the T8 vertebral level. Six direction diffusion weighted images (DWIs) were collected ex vivo along the length of the spinal cord, with an echo/repetition time of 31.6 ms/14 sec and b=500 sec/mm2. Diffusion metrics were correlated to hindlimb motor function. Significant differences were found for whole cord region of interest (ROI) drawings for fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusion coefficient (LD), and radial diffusion coefficient (RD) at each of the cervical levels (p<0.01). Motor function correlated with MD in the cervical segments of the spinal cord (r2=0.80). The diffusivity of water significantly decreased throughout “uninjured” portions of the spinal cord following a contusion injury (p<0.05). Diffusivity metrics were found to be altered following SCI in both white and gray matter regions. Injury severity was associated with diffusion changes over the entire length of the cord. This study demonstrates that DTI is sensitive to SCI in regions remote from injury, suggesting that the diffusion metrics may be used as a biomarker for severity of injury. PMID:23782233

Enrichment of spinal cord cell cultures with motoneurons

PubMed Central

1978-01-01

Spinal cord cell cultures contain several types of neurons. Two methods are described for enriching such cultures with motoneurons (defined here simply as cholinergic cells that are capable of innervating muscle). In the first method, 7-day embryonic chick spinal cord neurons were separated according to size by 1 g velocity sedimentation. It is assumed that cholinergic motoneurons are among the largest cells present at this stage. The spinal cords were dissociated vigorously so that 95-98% of the cells in the initial suspension were isolated from one another. Cells in leading fractions (large cell fractions: LCFs) contain about seven times as much choline acetyltransferase (CAT) activity per unit cytoplasm as do cells in trailing fractions (small cell fractions: SCFs). Muscle cultures seeded with LCFs develop 10-70 times as much CAT as cultures seeded with SCFs and six times as much CAT as cultures seeded with control (unfractionated) spinal cord cells. More than 20% of the large neurons in LCF-muscle cultures innervate nearby myotubes. In the second method, neurons were gently dissociated from 4-day embryonic spinal cords and maintained in vitro. This approach is based on earlier observations that cholinergic neurons are among the first cells to withdraw form the mitotic cycle in the developing chick embryo (Hamburger, V. 1948. J. Comp. Neurol. 88:221- 283; and Levi-Montalcini, R. 1950. J. Morphol. 86:253-283). 4-Day spinal cord-muscle cultures develop three times as much CAT as do 7-day spinal cord-muscle plates, prepared in the same (gentle) manner. More than 50% of the relatively large 4-day neurons innervate nearby myotubes. Thus, both methods are useful first steps toward the complete isolation of motoneurons. Both methods should facilitate study of the development of cholinergic neurons and of nerve-muscle synapse formation. PMID:566275

Isolated cytochrome c oxidase deficiency in G93A SOD1 mice overexpressing CCS protein.

PubMed

Son, Marjatta; Leary, Scot C; Romain, Nadine; Pierrel, Fabien; Winge, Dennis R; Haller, Ronald G; Elliott, Jeffrey L

2008-05-02

G93A SOD1 transgenic mice overexpressing CCS protein develop an accelerated disease course that is associated with enhanced mitochondrial pathology and increased mitochondrial localization of mutant SOD1. Because these results suggest an effect of mutant SOD1 on mitochondrial function, we assessed the enzymatic activities of mitochondrial respiratory chain complexes in the spinal cords of CCS/G93A SOD1 and control mice. CCS/G93A SOD1 mouse spinal cord demonstrates a 55% loss of complex IV (cytochrome c oxidase) activity compared with spinal cord from age-matched non-transgenic or G93A SOD1 mice. In contrast, CCS/G93A SOD1 spinal cord shows no reduction in the activities of complex I, II, or III. Blue native gel analysis further demonstrates a marked reduction in the levels of complex IV but not of complex I, II, III, or V in spinal cords of CCS/G93A SOD1 mice compared with non-transgenic, G93A SOD1, or CCS/WT SOD1 controls. With SDS-PAGE analysis, spinal cords from CCS/G93A SOD1 mice showed significant decreases in the levels of two structural subunits of cytochrome c oxidase, COX1 and COX5b, relative to controls. In contrast, CCS/G93A SOD1 mouse spinal cord showed no reduction in levels of selected subunits from complexes I, II, III, or V. Heme A analyses of spinal cord further support the existence of cytochrome c oxidase deficiency in CCS/G93A SOD1 mice. Collectively, these results establish that CCS/G93A SOD1 mice manifest an isolated complex IV deficiency which may underlie a substantial part of mutant SOD1-induced mitochondrial cytopathy.

Inflammatory response to Escherichia coli urinary tract infection in the neurogenic bladder of the spinal cord injured host.

PubMed

Chaudhry, Rajeev; Madden-Fuentes, Ramiro J; Ortiz, Tara K; Balsara, Zarine; Tang, Yuping; Nseyo, Unwanaobong; Wiener, John S; Ross, Sherry S; Seed, Patrick C

2014-05-01

Urinary tract infections cause significant morbidity in patients with spinal cord injury. An in vivo spinal cord injured rat model of experimental Escherichia coli urinary tract infection mimics human disease with enhanced susceptibility to urinary tract infection compared to controls. We hypothesized that a dysregulated inflammatory response contributes to enhanced susceptibility to urinary tract infection. Spinal cord injured and sham injured rats were inoculated transurethrally with E. coli. Transcript levels of 84 inflammatory pathway genes were measured in bladder tissue of each group before infection, 24 hours after infection and after 5 days of antibiotic therapy. Before infection quantitative polymerase chain reaction array revealed greater than twofold up-regulation in the proinflammatory factor transcripts slc11a1, ccl4 and il1β, and down-regulation of the antimicrobial peptides lcn2 and mpo in spinal cord injured vs control bladders. At 24 hours after infection spinal cord injured bladders showed an attenuated innate immune response with decreased expression of il6, slc11a1, il1β and lcn2, and decreased il10 and slpi expression compared to controls. Despite clearance of bacteriuria with antibiotics spinal cord injured rats had delayed induction of il6 transcription and a delayed anti-inflammatory response with decreased il10 and slpi transcript levels relative to controls. Spinal cord injured bladders fail to mount a characteristic inflammatory response to E. coli infection and cannot suppress inflammation after infection is eliminated. This may lead to increased susceptibility to urinary tract infection and persistent chronic inflammation through neural mediated pathways, which to our knowledge remain to be defined. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2017-01-01

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

Production of high quality brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) RNA from isolated populations of rat spinal cord motor neurons obtained by Laser Capture Microdissection (LCM).

PubMed

Mehta, Prachi; Premkumar, Brian; Morris, Renée

2016-08-03

The mammalian central nervous system (CNS) is composed of multiple cellular elements, making it challenging to segregate one particular cell type to study their gene expression profile. For instance, as motor neurons represent only 5-10% of the total cell population of the spinal cord, meaningful transcriptional analysis on these neurons is almost impossible to achieve from homogenized spinal cord tissue. A major challenge faced by scientists is to obtain good quality RNA from small amounts of starting material. In this paper, we used Laser Capture Microdissection (LCM) techniques to identify and isolate spinal cord motor neurons. The present analysis revealed that perfusion with paraformaldehyde (PFA) does not alter RNA quality. RNA integrity numbers (RINs) of tissue samples from rubrospinal tract (RST)-transected, intact spinal cord or from whole spinal cord homogenate were all above 8, which indicates intact, high-quality RNA. Levels of mRNA for brain-derived neurotrophic factor (BDNF) or for its tropomyosin receptor kinase B (TrkB) were not affected by rubrospinal tract (RST) transection, a surgical procedure that deprive motor neurons from one of their main supraspinal input. The isolation of pure populations of neurons with LCM techniques allows for robust transcriptional characterization that cannot be achieved with spinal cord homogenates. Such preparations of pure population of motor neurons will provide valuable tools to advance our understanding of the molecular mechanisms underlying spinal cord injury and neuromuscular diseases. In the near future, LCM techniques might be instrumental to the success of gene therapy for these debilitating conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of electroacupuncture and the retinoid X receptor (RXR) signalling pathway on oligodendrocyte differentiation in the demyelinated spinal cord of rats

PubMed Central

Yang, Xiao-Hua; Ding, Ying; Li, Wen; Zhang, Rong-Yi; Wu, Jin-Lang; Ling, Eng-Ang; Wu, Wutian

2017-01-01

Objectives In spinal cord demyelination, some oligodendrocyte precursor cells (OPCs) remain in the demyelinated region but have a reduced capacity to differentiate into oligodendrocytes. This study investigated whether ‘Governor Vessel’ (GV) electroacupuncture (EA) would promote the differentiation of endogenous OPCs into oligodendrocytes by activating the retinoid X receptor γ (RXR-γ)-mediated signalling pathway. Methods Adult rats were microinjected with ethidium bromide (EB) into the T10 spinal cord to establish a model of spinal cord demyelination. EB-injected rats remained untreated (EB group, n=26) or received EA treatment (EB+EA group, n=26). A control group (n=26) was also included that underwent dural exposure without EB injection. After euthanasia at 7 days (n=5 per group), 15 days (n=8 per group) or 30 days (n=13 per group), protein expression of RXR-γ in the demyelinated spinal cord was evaluated by immunohistochemistry and Western blotting. In addition, OPCs derived from rat embryonic spinal cord were cultured in vitro, and exogenous 9-cis-RA (retinoic acid) and RXR-γ antagonist HX531 were administered to determine whether RA could activate RXR-γ and promote OPC differentiation. Results EA was found to increase the numbers of both OPCs and oligodendrocytes expressing RXR-γ and RALDH2, and promote remyelination in the remyelinated spinal cord. Exogenous 9-cis-RA enhanced the differentiation of OPCs into mature oligodendrocytes by activating RXR-γ. Conclusions The results suggest that EA may activate RXR signalling to promote the differentiation of OPCs into oligodendrocytes in spinal cord demyelination. PMID:27841975

Preexisting severe cervical spinal cord compression is a significant risk factor for severe paralysis development in patients with traumatic cervical spinal cord injury without bone injury: a retrospective cohort study.

PubMed

Oichi, Takeshi; Oshima, Yasushi; Okazaki, Rentaro; Azuma, Seiichi

2016-01-01

The objective of this study is to investigate whether preexisting severe cervical spinal cord compression affects the severity of paralysis once patients develop traumatic cervical spinal cord injury (CSCI) without bone injury. We retrospectively investigated 122 consecutive patients with traumatic CSCI without bone injury. The severity of paralysis on admission was assessed by the American Spinal Injury Association impairment scale (AIS). The degree of preexisting cervical spinal cord compression was evaluated by the maximum spinal cord compression (MSCC) and was divided into three categories: minor compression (MSCC ≤ 20 %), moderate compression (20 % < MSCC ≤ 40 %), and severe compression (40 % < MSCC). We investigated soft-tissue damage on magnetic resonance imaging to estimate the external force applied. Other potential risk factors, including age, sex, fused vertebra, and ossification of longitudinal ligament, were also reviewed. A multivariate logistic regression analysis was performed to investigate the risk factors for developing severe paralysis (AIS A-C) on admission. Our study included 103 males and 19 females with mean age of 65 years. Sixty-one patients showed severe paralysis (AIS A-C) on admission. The average MSCC was 22 %. Moderate compression was observed in 41, and severe in 20. Soft-tissue damage was observed in 91. A multivariate analysis showed that severe cervical spinal cord compression significantly affected the severity of paralysis at the time of injury, whereas both mild and moderate compression did not affect it. Soft-tissue damage was also significantly associated with severe paralysis on admission. Preexisting severe cervical cord compression is an independent risk factor for severe paralysis once patients develop traumatic CSCI without bone injury.

Convection-enhanced delivery of a hydrophilic nitrosourea ameliorates deficits and suppresses tumor growth in experimental spinal cord glioma models.

PubMed

Ogita, Shogo; Endo, Toshiki; Sugiyama, Shinichiro; Saito, Ryuta; Inoue, Tomoo; Sumiyoshi, Akira; Nonaka, Hiroi; Kawashima, Ryuta; Sonoda, Yukihiko; Tominaga, Teiji

2017-05-01

Convection-enhanced delivery (CED) is a technique allowing local infusion of therapeutic agents into the central nervous system, circumventing the blood-brain or spinal cord barrier. To evaluate the utility of nimustine hydrochloride (ACNU) CED in controlling tumor progression in an experimental spinal cord glioma model. Toxicity studies were performed in 42 rats following the administration of 4 μl of ACNU CED into the mid-thoracic spinal cord at concentrations ranging from 0.1 to 10 mg/ml. Behavioral analyses and histological evaluations were performed to assess ACNU toxicity in the spinal cord. A survival study was performed in 32 rats following the implantation of 9 L cells into the T8 spinal cord. Seven days after the implantation, rats were assigned to four groups: ACNU CED (0.25 mg/ml; n = 8); ACNU intravenous (i.v.) (0.4 mg; n = 8); saline CED (n = 8); saline i.v. (n = 8). Hind limb movements were evaluated daily in all rats for 21 days. Tumor sizes were measured histologically. The maximum tolerated ACNU concentration was 0.25 mg/ml. Preservation of hind limb motor function and tumor growth suppression was observed in the ACNU CED (0.25 mg/ml) and ACNU i.v. groups. Antitumor effects were more prominent in the ACNU CED group especially in behavioral analyses (P < 0.05; log-rank test). ACNU CED had efficacy in controlling tumor growth and preserving neurological function in an experimental spinal cord tumor model. ACNU CED can be a viable treatment option for spinal cord high-grade glioma.

Release of neuropeptide FF (FLFQPQRF-NH2) from rat spinal cord.

PubMed

Zhu, J; Jhamandas, K; Yang, H Y

1992-10-02

Neuropeptide FF (FLFQPQRF-NH2), originally isolated from bovine brain, is an FMRF-NH2-like peptide with morphine-modulating activity. Neuropeptide FF (NPFF) is highly localized in the dorsal spinal cords where there are also specific NPFF binding sites. Furthermore, there have been studies indicating that NPFF may participate in the regulation of pain threshold in the spinal cord. However, whether NPFF can be released from the spinal cord is not known. The present experiments, using an in vitro superfusion of an isolated whole rat spinal cord, demonstrated that high concentrations of KCl or substance P caused a release of NPFF immunoreactive material (IR) from the spinal cord into the perfusion medium in a calcium-dependent manner. Substance P (1-11) also produced a detectable release of NPFF-IR in vivo although the response was quite variable. The released NPFF-IR was analyzed by an HPLC study and found to consist of NPFF and other minor immunoreactive peptides. Further studies with substance P-related peptides showed that the in vitro release of NPFF-IR could also be induced by substance P (1-7) but not by [pGlu5,Me-Phe8,Sar9]-substance P (5-11) or substance K. These results suggest that the specific substance P receptor (SP-N), which is recognized by both substance P (1-11) and substance P (1-7) rather than the tachykinin receptor, is involved in NPFF secretion from the spinal cord. In view of the role of substance P (1-11) and substance P (1-7) in sensory transmission, the results of this study further support the role of NPFF in the modulation of antinociception in the spinal cord.

Cycling exercise and fetal spinal cord transplantation act synergistically on atrophied muscle following chronic spinal cord injury in rats.

PubMed

Peterson, C A; Murphy, R J; Dupont-Versteegden, E E; Houlé, J D

2000-01-01

The potential of two interventions, alone or in combination, to restore chronic spinal cord transection-induced changes in skeletal muscles of adult Sprague-Dawley rats was studied. Hind limb skeletal muscles were examined in the following groups of animals: rats with a complete spinal cord transection (Tx) for 8 weeks; Tx with a 4-week delay before initiation of a 4-week motor-assisted cycling exercise (Ex) program; Tx with a 4-week delay before transplantation (Tp) of fetal spinal cord tissue into the lesion cavity; Tx with a 4-week delay before Tp and Ex; and uninjured control animals. Muscle mass, muscle to body mass ratios, and mean myofiber cross-sectional areas were significantly reduced 8 weeks after transection. Whereas transplantation of fetal spinal cord tissue did not reverse this atrophy and exercise alone had only a modest effect in restoring lost muscle mass, the combination of exercise and transplantation significantly increased muscle mass, muscle to body mass ratios, and mean myofiber cross-sectional areas in both soleus and plantaris muscles. Spinal cord injury (SCI) also caused changes in myosin heavy chain (MyHC) expression toward faster isoforms in both soleus and plantaris and increased soleus myofiber succinate dehydrogenase (SDH) activity. Combined exercise and transplantation led to a change in the expression of the fastest MyHC isoform in soleus but had no effect in the plantaris. Exercise alone and in combination with transplantation reduced SDH activity to control levels in the soleus. These results suggest a synergistic action of exercise and transplantation of fetal spinal cord tissue on skeletal muscle properties following SCI, even after an extended post-injury period before intervention.

Involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters in neonatal rat spinal cord.

PubMed Central

Suzuki, H; Yoshioka, K; Yanagisawa, M; Urayama, O; Kurihara, T; Hosoki, R; Saito, K; Otsuka, M

1994-01-01

1. The possible involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters was examined in the spinal cord of the neonatal rat. 2. The magnitude of substance P (SP)- or neurokinin A (NKA)-evoked depolarization of a lumbar ventral root in the isolated spinal cord preparation was increased by a mixture of peptidase inhibitors, consisting of actinonin (6 microM), arphamenine B (6 microM), bestatin (10 microM), captopril (10 microM) and thiorphan (0.3 microM). The mixture augmented the response to NKA more markedly than that to SP. 3. In the isolated spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow depolarization of the L3 ventral root was augmented by the mixture of peptidase inhibitors in the presence of naloxone (0.5 microM) but not in the presence of both naloxone and a tachykinin receptor antagonist, GR71251 (5 microM). 4. Application of capsaicin (0.5 microM) for 6 min to the spinal cord evoked an increase in the release of SP from the spinal cord. The amount of SP released was significantly augmented by the mixture of peptidase inhibitors. 5. Synaptic membrane fractions were prepared from neonatal rat spinal cords. These fractions showed degrading activities for SP and NKA and the activities were inhibited by the mixture of peptidase inhibitors. The degrading activity for NKA was higher than that for SP and the inhibitory effect of the mixture for NKA was more marked than that for SP. Although some other fractions obtained from homogenates of spinal cords showed higher degrading activities for SP, these activities were insensitive to the mixture of peptidase inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7529113

Spinal cord lesions in Bangladesh: an epidemiological study 1994 - 1995.

PubMed

Hoque, M F; Grangeon, C; Reed, K

1999-12-01

Spinal Cord Lesions are a major public health problem in Bangladesh. This epidemiological study was undertaken in order to identify the causes of spinal cord lesions and thus to allow prevention and control programs to be developed. The records of 247 patients with spinal cord lesions admitted to The Centre for the Rehabilitation of the Paralysed (CRP), Savar, Dhaka from January 1994 to June 1995 were reviewed retrospectively. Comparisons were made with the reports of studies from other countries, both developing and developed. The most common cause of traumatic lesions was a fall from a height followed by falling when carrying a heavy weight on the head and road traffic accidents. Most of the patients were between 20 - 40 years old and the overall age group ranged from 10 - 70 years. The male:female ratio was 7.5 : 1.0. Among the traumatic spinal cord lesions, 60% were paraplegics and 40% tetraplegics. Among the non-traumatic spinal cord lesions cases 84% were paraplegics and 16% tetraplegics. The leading cause of death resulted from respiratory complications and these deaths occurred in the very early period of admission. From the results it can be deduced that the high incidence of spinal cord lesion as a result from falls from a height, and from falling when carrying a heavy weight on the head, can be explained by the mainly agricultural based economy of Bangladesh. The most common age group (10 - 40 years) of patients reflects the socio-economic conditions of Bangladesh. The male:female ratio (7.5 : 1.0) of patients with a spinal cord lesion is due to the socio-economic status and to the traditional culture of the society.

Agmatine Modulates the Phenotype of Macrophage Acute Phase after Spinal Cord Injury in Rats.

PubMed

Kim, Jae Hwan; Kim, Jae Young; Mun, Chin Hee; Suh, Minah; Lee, Jong Eun

2017-10-01

Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macrophage has subtypes, M1 and M2 macrophages. M1 macrophage induces a pro-inflammatory response, but M2 inspires an anti-inflammatory response. In this study, it was clarified whether the neuroprotective effect of agmatine is related with the modulation of macrophage subdivision after spinal cord injury. Spinal cord injury was induced in rats with contusion using MASCIS. Animals received agmatine (100 mg/kg, IP) daily for 6 days beginning the day after spinal cord injury. The proportion of M1 and M2 macrophages are confirmed with immunohistochemistry and FACS. CD206 + & ED1 + cells were counted as M2 macrophages. The systemic treatment of agmatine increased M2 macrophages caudal side to epicenter 1 week after spinal cord injury in immunohistochemistry. M2 macrophage related markers, Arginase-1 and CD206 mRNA, were increased in the agmatine treatment group and M2 macrophage expressing and stimulated cytokine, IL-10 mRNA, also was significantly overexpressed by agmatine injection. Among BMPs, BMP2/4/7, agmatine significantly increased only the expression of BMP2 known to reduce M1 macrophage under inflammatory status. These results suggest that agmatine reduces impairment after spinal cord injury through modulating the macrophage phenotype.

Agmatine Modulates the Phenotype of Macrophage Acute Phase after Spinal Cord Injury in Rats

PubMed Central

Kim, Jae Young; Mun, Chin Hee; Suh, Minah

2017-01-01

Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macrophage has subtypes, M1 and M2 macrophages. M1 macrophage induces a pro-inflammatory response, but M2 inspires an anti-inflammatory response. In this study, it was clarified whether the neuroprotective effect of agmatine is related with the modulation of macrophage subdivision after spinal cord injury. Spinal cord injury was induced in rats with contusion using MASCIS. Animals received agmatine (100 mg/kg, IP) daily for 6 days beginning the day after spinal cord injury. The proportion of M1 and M2 macrophages are confirmed with immunohistochemistry and FACS. CD206+ & ED1+ cells were counted as M2 macrophages. The systemic treatment of agmatine increased M2 macrophages caudal side to epicenter 1 week after spinal cord injury in immunohistochemistry. M2 macrophage related markers, Arginase-1 and CD206 mRNA, were increased in the agmatine treatment group and M2 macrophage expressing and stimulated cytokine, IL-10 mRNA, also was significantly overexpressed by agmatine injection. Among BMPs, BMP2/4/7, agmatine significantly increased only the expression of BMP2 known to reduce M1 macrophage under inflammatory status. These results suggest that agmatine reduces impairment after spinal cord injury through modulating the macrophage phenotype. PMID:29093636

Spinal cord ischemia after simultaneous and sequential treatment of multilevel aortic disease.

PubMed

Piffaretti, Gabriele; Bonardelli, Stefano; Bellosta, Raffaello; Mariscalco, Giovanni; Lomazzi, Chiara; Tolenaar, Jip L; Zanotti, Camilla; Guadrini, Cristina; Sarcina, Antonio; Castelli, Patrizio; Trimarchi, Santi

2014-10-01

The aim of the present study is to report a risk analysis for spinal cord injury in a recent cohort of patients with simultaneous and sequential treatment of multilevel aortic disease. We performed a multicenter study with a retrospective data analysis. Simultaneous treatment refers to descending thoracic and infrarenal aortic lesions treated during the same operation, and sequential treatment refers to separate operations. All descending replacements were managed with endovascular repair. Of 4320 patients, multilevel aortic disease was detected in 77 (1.8%). Simultaneous repair was performed in 32 patients (41.5%), and a sequential repair was performed in 45 patients (58.4%). Postoperative spinal cord injury developed in 6 patients (7.8%). At multivariable analysis, the distance of the distal aortic neck from the celiac trunk was the only independent predictor of postoperative spinal cord injury (odds ratio, 0.75; 95% confidence interval, 0.56-0.99; P=.046); open surgical repair of the abdominal aortic disease was associated with a higher risk of spinal cord injury but did not reach statistical significance (odds ratio, 0.16; 95% confidence interval, 0.02-1.06; P=.057). Actuarial survival estimates at 1, 2, and 5 years after the procedure were 80%±5%, 68%±6%, and 63%±7%, respectively. Spinal cord injury did not impair survival (P=.885). In our experience, the risk of spinal cord injury is still substantial at 8% in patients with multilevel aortic disease. The distance of the distal landing zone from the celiac trunk is a significant predictor of spinal cord ischemia. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

GDNF and NGF family members and receptors in human fetal and adult spinal cord and dorsal root ganglia.

PubMed

Josephson, A; Widenfalk, J; Trifunovski, A; Widmer, H R; Olson, L; Spenger, C

2001-11-12

We describe the expression of mRNA encoding ligands and receptors of members of the GDNF family and members of the neurotrophin family in the adult human spinal cord and dorsal root ganglia (DRG). Fetal human spinal cord and ganglia were investigated for the presence of ligands and receptors of the neurotrophin family. Tissues were collected from human organ donors and after routine elective abortions. Messenger RNA was found encoding RET, GFR alpha-1, BDNF, trkB, and trkC in the adult human spinal cord and BDNF, NT-3, p75, trkB, and trkC in the fetal human spinal cord. The percentage of adult human DRG cells expressing p75, trkA, trkB, or trkC was 57, 46, 29, and 24%, respectively, and that of DRG cells expressing RET, GFR alpha-1, GFR alpha-2, or GFR alpha-3 was 79, 20, 51, and 32%, respectively. GFR alpha-2 was expressed selectively in small, GFR alpha-3 principally in small and GFR alpha-1 and RET in both large and small adult human DRG neurons. p75 and trkB were expressed by a wide range of DRG neurons while trkA was expressed in most small diameter and trkC primarily in large DRG neurons. Fetal DRG cells were positive for the same probes as adult DRG cells except for NT-3, which was only found in fetal DRG cells. Messenger RNA species only expressed at detectable levels in fetal but not adult spinal cord tissues included GDNF, GFR alpha-2, NT-3, and p75. Notably, GFR alpha-2, which is expressed in the adult rat spinal cord, was not found in the adult human spinal cord. Copyright 2001 Wiley-Liss, Inc.

Brain and cord myelin water imaging: a progressive multiple sclerosis biomarker

PubMed Central

Kolind, Shannon; Seddigh, Arshia; Combes, Anna; Russell-Schulz, Bretta; Tam, Roger; Yogendrakumar, Vignan; Deoni, Sean; Sibtain, Naomi A.; Traboulsee, Anthony; Williams, Steven C.R.; Barker, Gareth J.; Brex, Peter A.

2015-01-01

Objectives Conventional magnetic resonance imaging (MRI) is used to diagnose and monitor inflammatory disease in relapsing remitting (RR) multiple sclerosis (MS). In the less common primary progressive (PP) form of MS, in which focal inflammation is less evident, biomarkers are still needed to enable evaluation of novel therapies in clinical trials. Our objective was to characterize the association — across the brain and cervical spinal cord — between clinical disability measures in PPMS and two potential biomarkers (one for myelin, and one for atrophy, both resulting from the same imaging technique). Methods Multi-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) MRI of the brain and cervical spinal cord were obtained for 15 PPMS patients and 11 matched controls. Data were analysed to estimate the signal related to myelin water (VFM), as well as volume measurements. MS disability was assessed using the Multiple Sclerosis Functional Composite score, which includes measures of cognitive processing (Paced Auditory Serial Addition Test), manual dexterity (9-Hole Peg Test) and ambulatory function (Timed 25-Foot Walk); and the Expanded Disability Status Scale. Results Brain and spinal cord volumes were different in PPMS compared to controls, particularly ventricular (+ 46%, p = 0.0006) and cervical spinal cord volume (− 16%, p = 0.0001). Brain and spinal cord myelin (VFM) were also reduced in PPMS (brain: − 11%, p = 0.01; spine: − 19%, p = 0.000004). Cognitive processing correlated with brain ventricular volume (p = 0.009). Manual dexterity correlated with brain ventricular volume (p = 0.007), and both brain and spinal cord VFM (p = 0.01 and 0.06, respectively). Ambulation correlated with spinal cord volume (p = 0.04) and spinal cord VFM (p = 0.04). Interpretation In this study we demonstrated that mcDESPOT can be used to measure myelin and atrophy in the brain and spinal cord. Results correlate well with clinical disability scores in PPMS representing cognitive, fine motor and ambulatory disability. PMID:26594633

Altered spinal cord activity during sexual stimulation in women with SCI: a pilot fMRI study.

PubMed

Alexander, Marcalee; Kozyrev, Natalie; Figley, Chase R; Richards, J Scott

2017-01-01

The objective of this study was to assess the feasibility of the use of functional magnetic resonance imaging (fMRI) to evaluate the spinal activation during sexual response of the thoracic, lumbar and sacral spinal cord. This is a laboratory-based pilot study in human females at a University-based medical center in the United States. In three healthy spinal cord injury (SCI) females, spinal cord activations during sexual audiovisual stimulation (alone), genital self-stimulation (alone) and simultaneous audiovisual and genital self-stimulation (combined) were assessed and then compared with each subjects' remaining sensory and motor function. Spinal fMRI responses of the intermediolateral columns were found during audiovisual stimulation in both subjects with incomplete injuries, but they were not observed in the subject with a complete injury. Moreover, sacral responses to combined stimulation differed greatly between the subjects with complete and incomplete injuries. These results not only provide the first in vivo documentation of spinal fMRI responses associated with sexual arousal in women with SCIs, but also suggest that spinal cord fMRI is capable of distinguishing between injury subtypes. Therefore, although there are certain limitations associated with fMRI during sexual stimulation (for example, movement artifacts, an artificially controlled environment and so), these findings demonstrate the potential utility of incorporating spinal cord fMRI in future research to evaluate the impact of specific patterns of SCI on sexual responses and/or the effects of treatment.

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

PubMed

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

2016-09-01

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

Effects of glycine on motor performance in rats after traumatic spinal cord injury.

PubMed

Gonzalez-Piña, Rigoberto; Nuño-Licona, Alberto

2007-01-01

It has been reported that glycine improves some functions lost after spinal cord injury (SCI). In order to assess the effects of glycine administration on motor performance after SCI, we used fifteen male Wistar rats distributed into three groups: sham (n = 3), spinal-cord injury (n = 6,) and spinal cord injury + glycine (n = 6). Motor performance was assessed using the beam-walking paradigm and footprint analysis. Results showed that for all animals with spinal-cord injury, scores in the beam-walking increased, which is an indication of increased motor deficit. In addition, footprint analysis showed a decrease in stride length and an increase in stride angle, additional indicators of motor deficit. These effects trended towards recovery after 8 weeks of recording and trended toward improvement by glycine administration; the effect was not significant. These results suggest that glycine replacement alone is not sufficient to improve the motor deficits that occur after SCI.

Thoracic arachnoid cyst resection.

PubMed

Deutsch, Harel

2014-09-01

Arachnoid cysts in the spinal cord may be asymptomatic. In some cases arachnoid cysts may exert mass effect on the thoracic spinal cord and lead to pain and myelopathy symptoms. Arachnoid cysts may be difficult to visualize on an MRI scan because the thin walled arachnoid may not be visible. Focal displacement of the thoracic spinal cord and effacement of the spinal cord with apparent widening of the cerebrospinal fluid space is seen. This video demonstrates surgical techniques to remove a dorsal arachnoid cyst causing spinal cord compression. The surgery involves a thoracic laminectomy. The dura is opened sharply with care taken not to open the arachnoid so that the cyst can be well visualized. The thickened arachnoid walls of the cyst are removed to alleviate the compression caused by the arachnoid cyst. The video can be found here: http://youtu.be/pgUrl9xvsD0.

Modeling the neuroanatomic propagation of ALS in the spinal cord

NASA Astrophysics Data System (ADS)

Drawert, Brian; Thakore, Nimish; Mitchell, Brian; Pioro, Erik; Ravits, John; Petzold, Linda R.

2017-07-01

Recent hypotheses of amyotrophic lateral sclerosis (ALS) progression have posited a point-source origin of motor neuron death with neuroanatomic propagation either contiguously to adjacent regions, or along networks via axonal and synaptic connections. Although the molecular mechanisms of propagation are unknown, one leading hypothesis is a "prion-like" spread of misfolded and aggregated proteins, including SOD1 and TDP-43. We have developed a mathematical model representing cellular and molecular spread of ALS in the human spinal cord. Our model is based on the stochastic reaction-diffusion master equation approach using a tetrahedral discretized space to capture the complex geometry of the spinal cord. Domain dimension and shape was obtained by reconstructing human spinal cord from high-resolution magnetic resonance (MR) images and known gross and histological neuroanatomy. Our preliminary results qualitatively recapitulate the clinically observed pattern of spread of ALS thorough the spinal cord.

Spinal cord lesions of progressive multifocal leukoencephalopathy in an acquired immunodeficiency syndrome patient.

PubMed

Bernal-Cano, F; Joseph, J T; Koralnik, I J

2007-10-01

Progressive multifocal leukoencephalopathy (PML) is a deadly demyelinating disease of the central nervous system, which occurs in immunosuppressed individuals. This disease is caused by a reactivation of the polyomavirus JC (JCV). Clinical presentation can be variable from patient to patient as lesions can occur anywhere in the CNS white matter; however, they appear to spare the optic nerves and the spinal cord. The authors present a case of PML in the setting of acquired immunodeficiency syndrome (AIDS) who developed PML lesions in the spinal cord, discovered during the postmortem examination. This finding is significant because PML has recently been diagnosed in patients with multiple sclerosis (MS) treated with the novel immunomodulatory medication natalizumab. Indeed, spinal cord lesions are frequent in MS. Therefore clinicians should be aware that in addition to the brain, PML may also affect the spinal cord white matter.

Interfacing peripheral nerve with macro-sieve electrodes following spinal cord injury.

PubMed

Birenbaum, Nathan K; MacEwan, Matthew R; Ray, Wilson Z

2017-06-01

Macro-sieve electrodes were implanted in the sciatic nerve of five adult male Lewis rats following spinal cord injury to assess the ability of the macro-sieve electrode to interface regenerated peripheral nerve fibers post-spinal cord injury. Each spinal cord injury was performed via right lateral hemisection of the cord at the T 9-10 site. Five months post-implantation, the ability of the macro-sieve electrode to interface the regenerated nerve was assessed by stimulating through the macro-sieve electrode and recording both electromyography signals and evoked muscle force from distal musculature. Electromyography measurements were recorded from the tibialis anterior and gastrocnemius muscles, while evoked muscle force measurements were recorded from the tibialis anterior, extensor digitorum longus, and gastrocnemius muscles. The macro-sieve electrode and regenerated sciatic nerve were then explanted for histological evaluation. Successful sciatic nerve regeneration across the macro-sieve electrode interface following spinal cord injury was seen in all five animals. Recorded electromyography signals and muscle force recordings obtained through macro-sieve electrode stimulation confirm the ability of the macro-sieve electrode to successfully recruit distal musculature in this injury model. Taken together, these results demonstrate the macro-sieve electrode as a viable interface for peripheral nerve stimulation in the context of spinal cord injury.

Percutaneous Radiofrequency Ablation of Painful Spinal Tumors Adjacent to the Spinal Cord with Real-Time Monitoring of Spinal Canal Temperature: A Prospective Study

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

Nakatsuka, Atsuhiro, E-mail: nakatuka@clin.medic.mie-u.ac.jp; Yamakado, Koichiro; Takaki, Haruyuki

2009-01-15

PurposeTo prospectively evaluate the feasibility, safety, and clinical utility of bone radiofrequency (RF) ablation with real-time monitoring of the spinal canal temperature for the treatment of spinal tumors adjacent to the spinal cord.Materials and MethodsOur Institutional Review Board approved this study. Patients gave informed consent. The inclusion criteria were (a) a painful spinal metastasis and (b) a distance of 1 cm or less between the metastasis and the spinal cord. The thermocouple was placed in the spinal canal under CT fluoroscopic guidance. When the spinal canal temperature reached 45{sup o}C, RF application was immediately stopped. RF ablation was considered technicallymore » successful when the procedure was performed without major complications. Clinical success was defined as a fall in the visual analogue scale score of at least 2 points.ResultsTen patients with spinal tumors measuring 3-8 cm (mean, 4.9 {+-} 1.5 cm) were enrolled. The distance between the tumor and the spinal cord was 1-6 mm (mean, 2.4 {+-} 1.6 mm). All procedures were judged technically successful (100%). The spinal canal temperature did not exceed 45{sup o}C in 9 of the 10 patients (90%). In the remaining patient, the temperature rose to 48{sup o}C, resulting in transient neural damage, although RF application was immediately stopped when the temperature reached 45{sup o}C. Clinical success was achieved within 1 week in all patients (100%).ConclusionBone RF ablation with real-time monitoring of the spinal canal temperature is feasible, safe, and clinically useful for the treatment of painful spinal metastases adjacent to the spinal cord.« less

Boomerang deformity of cervical spinal cord migrating between split laminae after laminoplasty.

PubMed

Kimura, S; Gomibuchi, F; Shimoda, H; Ikezawa, Y; Segawa, H; Kaneko, F; Uchiyama, S; Homma, T

2000-04-01

Patients with cervical compression myelopathy were studied to elucidate the mechanism underlying boomerang deformity, which results from the migration of the cervical spinal cord between split laminae after laminoplasty with median splitting of the spinous processes (boomerang sign). Thirty-nine cases, comprising 25 patients with cervical spondylotic myelopathy, 8 patients with ossification of the posterior longitudinal ligament, and 6 patients with cervical disc herniation with developmental canal stenosis, were examined. The clinical and radiological findings were retrospectively compared between patients with (B group, 8 cases) and without (C group, 31 cases) boomerang sign. Moderate increase of the grade of this deformity resulted in no clinical recovery, although there was no difference in clinical recovery between the two groups. Most boomerang signs developed at the C4/5 and/or C5/6 level, where maximal posterior movement of the spinal cord was achieved. Widths between lateral hinges and between split laminae in the B group were smaller than in the C group. Flatness of the spinal cord in the B group was more severe than in the C group. In conclusion, the boomerang sign was caused by posterior movement of the spinal cord, narrower enlargement of the spinal canal and flatness of the spinal cord.

Histopathologic correlation of magnetic resonance imaging signal patterns in a spinal cord injury model.

PubMed

Weirich, S D; Cotler, H B; Narayana, P A; Hazle, J D; Jackson, E F; Coupe, K J; McDonald, C L; Langford, L A; Harris, J H

1990-07-01

Magnetic resonance imaging (MRI) provides a noninvasive method of monitoring the pathologic response to spinal cord injury. Specific MR signal intensity patterns appear to correlate with degrees of improvement in the neurologic status in spinal cord injury patients. Histologic correlation of two types of MR signal intensity patterns are confirmed in the current study using a rat animal model. Adult male Sprague-Dawley rats underwent spinal cord trauma at the midthoracic level using a weight-dropping technique. After laminectomy, 5- and 10-gm brass weights were dropped from designated heights onto a 0.1-gm impounder placed on the exposed dura. Animals allowed to regain consciousness demonstrated variable recovery of hind limb paraplegia. Magnetic resonance images were obtained from 2 hours to 1 week after injury using a 2-tesla MRI/spectrometer. Sacrifice under anesthesia was performed by perfusive fixation; spinal columns were excised en bloc, embedded, sectioned, and observed with the compound light microscope. Magnetic resonance axial images obtained during the time sequence after injury demonstrate a distinct correlation between MR signal intensity patterns and the histologic appearance of the spinal cord. Magnetic resonance imaging delineates the pathologic processes resulting from acute spinal cord injury and can be used to differentiate the type of injury and prognosis.

Patient-focused goal planning process and outcome after spinal cord injury rehabilitation: quantitative and qualitative audit.

PubMed

Byrnes, Michelle; Beilby, Janet; Ray, Patricia; McLennan, Renee; Ker, John; Schug, Stephan

2012-12-01

To evaluate the process and outcome of a multidisciplinary inpatient goal planning rehabilitation programme on physical, social and psychological functioning for patients with spinal cord injury. Clinical audit: quantitative and qualitative analyses. Specialist spinal injury unit, Perth, Australia. Consecutive series of 100 newly injured spinal cord injury inpatients. MAIN MEASURE(S): The Needs Assessment Checklist (NAC), patient-focused goal planning questionnaire and goal planning progress form. The clinical audit of 100 spinal cord injured patients revealed that 547 goal planning meetings were held with 8531 goals stipulated in total. Seventy-five per cent of the goals set at the first goal planning meeting were achieved by the second meeting and the rate of goal achievements at subsequent goal planning meetings dropped to 56%. Based on quantitative analysis of physical, social and psychological functioning, the 100 spinal cord injury patients improved significantly from baseline to discharge. Furthermore, qualitative analysis revealed benefits consistently reported by spinal cord injury patients of the goal planning rehabilitation programme in improvements to their physical, social and psychological adjustment to injury. The findings of this clinical audit underpin the need for patient-focused goal planning rehabilitation programmes which are tailored to the individual's needs and involve a comprehensive multidisciplinary team.

Spinal cord compression in two related Ursus arctos horribilis.

PubMed

Thomovsky, Stephanie A; Chen, Annie V; Roberts, Greg R; Schmidt, Carrie E; Layton, Arthur W

2012-09-01

Two 15-yr-old grizzly bear littermates were evaluated within 9 mo of each other with the symptom of acute onset of progressive paraparesis and proprioceptive ataxia. The most significant clinical examination finding was pelvic limb paresis in both bears. Magnetic resonance examinations of both bears showed cranial thoracic spinal cord compression. The first bear had left-sided extradural, dorsolateral spinal cord compression at T3-T4. Vertebral canal stenosis was also observed at T2-T3. Images of the second bear showed lateral spinal cord compression from T2-T3 to T4-T5. Intervertebral disk disease and associated spinal cord compression was also observed at T2-T3 and T3-T4. One grizzly bear continued to deteriorate despite reduced exercise, steroid, and antibiotic therapy. The bear was euthanized, and a necropsy was performed. The postmortem showed a spinal ganglion cyst that caused spinal cord compression at the level of T3-T4. Wallerian-like degeneration was observed from C3-T6. The second bear was prescribed treatment that consisted of a combination of reduced exercise and steroid therapy. He continued to deteriorate with these medical therapies and was euthanized 4 mo after diagnosis. A necropsy showed hypertrophy and protrusion of the dorsal longitudinal ligament at T2-T3 and T3-T4, with resulting spinal cord compression in this region. Wallerian-like degeneration was observed from C2-L1. This is one of few case reports that describes paresis in bears. It is the only case report, to the authors' knowledge, that describes spinal magnetic resonance imaging findings in a grizzly bear and also the only report that describes a cranial thoracic myelopathy in two related grizzly bears with neurologic signs.

Cholinergic mechanisms in spinal locomotion—potential target for rehabilitation approaches

PubMed Central

Jordan, Larry M.; McVagh, J. R.; Noga, B. R.; Cabaj, A. M.; Majczyński, H.; Sławińska, Urszula; Provencher, J.; Leblond, H.; Rossignol, Serge

2014-01-01

Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a “hyper-cholinergic” state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in suppressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed by our experiments. PMID:25414645

Spinal Cord Gray Matter Atrophy in Amyotrophic Lateral Sclerosis.

PubMed

Paquin, M-Ê; El Mendili, M M; Gros, C; Dupont, S M; Cohen-Adad, J; Pradat, P-F

2018-01-01

There is an emerging need for biomarkers to better categorize clinical phenotypes and predict progression in amyotrophic lateral sclerosis. This study aimed to quantify cervical spinal gray matter atrophy in amyotrophic lateral sclerosis and investigate its association with clinical disability at baseline and after 1 year. Twenty-nine patients with amyotrophic lateral sclerosis and 22 healthy controls were scanned with 3T MR imaging. Standard functional scale was recorded at the time of MR imaging and after 1 year. MR imaging data were processed automatically to measure the spinal cord, gray matter, and white matter cross-sectional areas. A statistical analysis assessed the difference in cross-sectional areas between patients with amyotrophic lateral sclerosis and controls, correlations between spinal cord and gray matter atrophy to clinical disability at baseline and at 1 year, and prediction of clinical disability at 1 year. Gray matter atrophy was more sensitive to discriminate patients with amyotrophic lateral sclerosis from controls ( P = .004) compared with spinal cord atrophy ( P = .02). Gray matter and spinal cord cross-sectional areas showed good correlations with clinical scores at baseline ( R = 0.56 for gray matter and R = 0.55 for spinal cord; P < .01). Prediction at 1 year with clinical scores ( R 2 = 0.54) was improved when including a combination of gray matter and white matter cross-sectional areas ( R 2 = 0.74). Although improvements over spinal cord cross-sectional areas were modest, this study suggests the potential use of gray matter cross-sectional areas as an MR imaging structural biomarker to monitor the evolution of amyotrophic lateral sclerosis. © 2018 by American Journal of Neuroradiology.

Intraspinal AAV Injections Immediately Rostral to a Thoracic Spinal Cord Injury Site Efficiently Transduces Neurons in Spinal Cord and Brain

PubMed Central

Klaw, Michelle C; Xu, Chen; Tom, Veronica J

2013-01-01

In the vast majority of studies utilizing adeno-associated virus (AAV) in central nervous system applications, including those published with spinal cord injury (SCI) models, AAV has been administered at the level of the cell body of neurons targeted for genetic modification, resulting in transduction of neurons in the vicinity of the injection site. However, as SCI interrupts many axon tracts, it may be more beneficial to transduce a diverse pool of supraspinal neurons. We determined if descending axons severed by SCI are capable of retrogradely transporting AAV to remotely transduce a variety of brain regions. Different AAV serotypes encoding the reporter green fluorescent protein (GFP) were injected into gray and white matter immediately rostral to a spinal transection site. This resulted in the transduction of thousands of neurons within the spinal cord and in multiple regions within the brainstem that project to spinal cord. In addition, we established that different serotypes had disparate regional specificity and that AAV5 transduced the most brain and spinal cord neurons. This is the first demonstration that retrograde transport of AAV by axons severed by SCI is an effective means to transduce a collection of supraspinal neurons. Thus, we identify a novel, minimally invasive means to transduce a variety of neuronal populations within both the spinal cord and the brain following SCI. This paradigm to broadly distribute viral vectors has the potential to be an important component of a combinatorial strategy to promote functional axonal regeneration. PMID:23881451

Why New Spinal Cord Plasticity Does Not Disrupt Old Motor Behaviors.

PubMed

Chen, Yi; Chen, Lu; Wang, Yu; Chen, Xiang Yang; Wolpaw, Jonathan R

2017-08-23

When new motor learning changes the spinal cord, old behaviors are not impaired; their key features are preserved by additional compensatory plasticity. To explore the mechanisms responsible for this compensatory plasticity, we transected the spinal dorsal ascending tract before or after female rats acquired a new behavior-operantly conditioned increase or decrease in the right soleus H-reflex-and examined an old behavior-locomotion. Neither spinal dorsal ascending tract transection nor H-reflex conditioning alone impaired locomotion. Nevertheless, when spinal dorsal ascending tract transection and H-reflex conditioning were combined, the rats developed a limp and a tilted posture that correlated in direction and magnitude with the H-reflex change. When the right H-reflex was increased by conditioning, the right step lasted longer than the left and the right hip was higher than the left; when the right H-reflex was decreased by conditioning, the opposite occurred. These results indicate that ascending sensory input guides the compensatory plasticity that normally prevents the plasticity underlying H-reflex change from impairing locomotion. They support the concept of the state of the spinal cord as a negotiated equilibrium that reflects the concurrent influences of all the behaviors in an individual's repertoire; and they support the new therapeutic strategies this concept introduces. SIGNIFICANCE STATEMENT The spinal cord provides a reliable final common pathway for motor behaviors throughout life. Until recently, its reliability was explained by the assumption that it is hardwired; but it is now clear that the spinal cord changes continually as new behaviors are acquired. Nevertheless, old behaviors are preserved. This study shows that their preservation depends on sensory feedback from the spinal cord to the brain: if feedback is removed, the acquisition of a new behavior may disrupt an old behavior. In sum, when a new behavior changes the spinal cord, sensory feedback to the brain guides further change that preserves old behaviors. This finding contributes to a new understanding of spinal cord function and to development of new rehabilitation therapies. Copyright © 2017 the authors 0270-6474/17/378198-09$15.00/0.

The Role of Core Self-Evaluations in the Relationship between Stress and Depression in Persons with Spinal Cord Injury

ERIC Educational Resources Information Center

DeAngelis, Jesse B.; Yaghmaian, Rana; Smedema, Susan Miller

2016-01-01

Purpose: To investigate the role of core self-evaluations (CSE) in the relationship between perceived stress and depression in persons with spinal cord injury. Method: Two hundred forty-seven adults with spinal cord injury completed an online survey measuring perceived stress, CSE, and depressive symptoms. Results: A multiple regression analysis…

Frequency Mapping of Rat Spinal Cord at 7T

NASA Astrophysics Data System (ADS)

Chen, Evan; Rauscher, Alexander; Kozlowski, Piotr; Yung, Andrew

2012-10-01

The spinal cord is an integral part of the nervous system responsible for sensory, motor, and reflex control crucial to all bodily function. Due to its non-invasive nature, MRI is well matched for characterizing and imaging of spinal cord, and is used extensively for clinical applications. Recent developments in magnetic resonance imaging (MRI) at high field (7T) using phase represents a new approach of characterizing spinal cord myelin. Theory suggests that microstructure differences in myelinated white matter (WM) and non-myelinated gray matter (GM) affect MR phase, measurable frequency shifts. Data from pilot experiments using a multi-gradient echo (MGE) sequence to image rat spinal cords placed parallel to main magnetic field B0 has shown frequency shifts between not only between WM and GM, but also between specific WM tracts of the dorsal column, including the fasciculus gracilis, fasciculus cuneatus, and corticospinal tract. Using MGE, frequency maps at multiple echo times (TE) between 4ms and 22ms show a non-linear relationship between WM frequency, contrary to what was previously expected. These results demonstrate the effectiveness of MGE in revealing new information about spinal cord tissue microstructure, and lays important groundwork for in-vivo and human studies.

Sexuality and sexual life in women with spinal cord injury: a controlled study.

PubMed

Kreuter, Margareta; Siösteen, Agneta; Biering-Sørensen, Fin

2008-01-01

To describe sexual life in women with spinal cord injury. Controlled cross-sectional, questionnaire. Women, 18-65 years, treated at spinal cord centres in Sweden, Denmark, Norway, Finland and Iceland. 545 women (57%) completed the questionnaires. The age-matched control group consisted of 507 women. The 104-item Spinal Cord Injury Women Questionnaire, was designed to assess different dimensions of sexuality. 80% of the women with spinal cord injury had engaged in sex after the injury. Reasons for not wanting or not having the courage to be intimate and sexual were physical problems, low sexual desire, low self-esteem and feelings of being unattractive. The motivations of both the women with spinal cord injury and controls to engage in sexual activity were intimacy-based rather than primarily sexual. Being in the right mood both before and during sex to become receptive to sexual stimulation was important. For women who are able to overcome the physical restrictions and mental obstacles due to injury, it is possible to regain an active and positive sexual life together with a partner. Sexual information and counselling should be available both during initial rehabilitation and later when the women have returned to their homes.

Dynamic membrane depolarization is an early regulator of ependymoglial cell response to spinal cord injury in axolotl

PubMed Central

Sabin, Keith; Santos-Ferreira, Tiago; Essig, Jaclyn; Rudasill, Sarah; Echeverri, Karen

2016-01-01

Salamanders, such as the Mexican axolotl, are some of the few vertebrates fortunate in their ability to regenerate diverse structures after injury. Unlike mammals they are able to regenerate a fully functional spinal cord after injury. However, the molecular circuitry required to initiate a pro-regenerative response after spinal cord injury is not well understood. To address this question we developed a spinal cord injury model in axolotls and used in vivo imaging of labeled ependymoglial cells to characterize the response of these cells to injury. Using in vivo imaging of ion sensitive dyes we identified that spinal cord injury induces a rapid and dynamic change in the resting membrane potential of ependymoglial cells. Prolonged depolarization of ependymoglial cells after injury inhibits ependymoglial cell proliferation and subsequent axon regeneration. Using transcriptional profiling we identified c-Fos as a key voltage sensitive early response gene that is expressed specifically in the ependymoglial cells after injury. This data establishes that dynamic changes in the membrane potential after injury are essential for regulating the specific spatiotemporal expression of c-Fos that is critical for promoting faithful spinal cord regeneration in axolotl. PMID:26477559

Real-time PCR quantification of gene expression in embryonic mouse tissue.

PubMed

Villalon, Eric; Schulz, David J; Waters, Samuel T

2014-01-01

The Gbx family of transcription factors consists of two closely related proteins GBX1 and GBX2. A defining feature of the GBX family is a highly conserved 60 amino acid DNA-binding domain, which differs by just two amino acids. Gbx1 and Gbx2 are co-expressed in several areas of the developing central nervous system including the forebrain, anterior hindbrain, and spinal cord, suggesting the potential for genetic redundancy. However, there is a spatiotemporal difference in expression of Gbx1 and Gbx2 in the forebrain and spinal cord. Gbx2 has been shown to play a critical role in positioning the midbrain/hindbrain boundary and developing anterior hindbrain, whereas gene-targeting experiments in mice have revealed an essential function for Gbx1 in the spinal cord for normal locomotion. To determine if Gbx2 could potentially compensate for a loss of Gbx1 in the developing spinal cord, we performed real-time PCR to examine levels of Gbx2 expression in Gbx1(-/-) spinal cord at embryonic day (E) 13.5, a developmental stage when Gbx2 is rapidly downregulated. We demonstrate that Gbx2 expression is elevated in the spinal cord of Gbx1(-/-) embryos.

Site-specific gene transfer into the rat spinal cord by photomechanical waves

NASA Astrophysics Data System (ADS)

Ando, Takahiro; Sato, Shunichi; Toyooka, Terushige; Uozumi, Yoichi; Nawashiro, Hiroshi; Ashida, Hiroshi; Obara, Minoru

2011-10-01

Nonviral, site-specific gene delivery to deep tissue is required for gene therapy of a spinal cord injury. However, an efficient method satisfying these requirements has not been established. This study demonstrates efficient and targeted gene transfer into the spinal cord by using photomechanical waves (PMWs), which were generated by irradiating a black laser absorbing rubber with 532-nm nanosecond Nd:YAG laser pulses. After a solution of plasmid DNA coding for enhanced green fluorescent protein (EGFP) or luciferase was intraparenchymally injected into the spinal cord, PMWs were applied to the target site. In the PMW application group, we observed significant EGFP gene expression in the white matter and remarkably high luciferase activity only in the spinal cord segment exposed to the PMWs. We also assessed hind limb movements 24 h after the application of PMWs based on the Basso-Beattie-Bresnahan (BBB) score to evaluate the noninvasiveness of this method. Locomotor evaluation showed no significant decrease in BBB score under optimum laser irradiation conditions. These findings demonstrated that exogenous genes can be efficiently and site-selectively delivered into the spinal cord by applying PMWs without significant locomotive damage.

Development of serotonergic and adrenergic receptors in the rat spinal cord: effects of neonatal chemical lesions and hyperthyroidism.

PubMed

Lau, C; Pylypiw, A; Ross, L L

1985-03-01

The sympathetic preganglionic neurons in the spinal cord receive dense serotonergic (5-HT) and catecholaminergic (CA) afferent inputs from the descending supraspinal pathways. In the rat spinal cord, the levels of these biogenic amines and their receptors are low at birth, but undergo rapid ontogenetic increases in the ensuing 2-3 postnatal weeks until the adult levels are reached. In many systems it has been shown that denervation of presynaptic neurons leads to an up-regulation of the number of postsynaptic receptors. To determine whether the 5-HT and CA receptors in the developing spinal cord are also subject to such transsynaptic regulation, we examined the ontogeny of serotonergic receptors and alpha- and beta-adrenergic receptors in thoracolumbar spinal cord of rats given neurotoxins which destroy serotonergic (5,7-dihydroxytryptamine (5,7-DHT)) or noradrenergic (6-hydroxydopamine (6-OHDA)) nerve terminals. Intracisternal administration of 5,7-DHT or 6-OHDA at 1 and 6 days of age prevented, respectively, the development of 5-HT and CA levels in the spinal cord. Rats lesioned with 5,7-DHT displayed a marked elevation of 5-HT receptors with a binding of 50% greater than controls at 1 week and a continuing increase to twice normal by 4 weeks. A similar pattern of up-regulation was also detected with the alpha-adrenergic receptor, as rats lesioned with 6-OHDA exhibited persistent increases in receptor concentration. However, in these same animals ontogeny of the beta-adrenergic receptor in the spinal cord remained virtually unaffected by the chemical lesion. In several other parts of the nervous system, it has been demonstrated that the beta-adrenergic sensitivity can be modulated by hormonal signals, particularly that of the thyroid hormones. This phenomenon was examined in the spinal cord and in confirmation with previous studies neonatal treatment of triiodothyronine (0.1 mg/kg, s.c. daily) was capable of evoking persistent increases in beta-adrenergic receptor binding. These results suggest that: (a) development of the postjunctional serotonergic and alpha-adrenergic receptors in the rat spinal cord can occur in the absence of the prejunctional nerve terminals and are subject to transsynaptic modulation; (b) beta-adrenergic receptors in the spinal cord also can develop after prejunctional lesions but are regulated by hormonal rather than neuronal factors.

Transverse myelitis caused by hepatitis E: previously undescribed in adults

PubMed Central

Sarkar, Pamela; Morgan, Catherine; Ijaz, Samreen

2015-01-01

We report the case of a 62-year-old Caucasian woman who was admitted with urinary retention and lower limb paraesthesia following a week's prodromal illness of headache and malaise. Liver function tests showed a picture of acute hepatocellular dysfunction. She developed reduced lower limb power, brisk reflexes, extensor plantars, a sensory level at T8 and reduced anal sphincter tone, establishing a clinical diagnosis of transverse myelitis. A spinal MRI showed no evidence of cauda equina or spinal cord compression. Cerebrospinal fluid (CSF) analysis showed raised protein and raised white cell count. Hepatitis E IgM and IgG were positive and hepatitis E virus was found in her CSF. She was treated with methylprednisolone and is slowly recovering with physiotherapy. PMID:26150621

Microsurgical resection of intramedullary spinal cord ependymoma.

PubMed

McCormick, Paul C

2014-09-01

Ependymomas are the most commonly occurring intramedullary spinal cord tumor in adults. With few exceptions these tumors are histologically benign, although they exhibit some biologic variability with respect to growth rate. While unencapsulated, spinal ependymomas are non-infiltrative and present a clear margin of demarcation from the surrounding spinal cord that serves as an effective dissection plane. This video demonstrates the technique of microsurgical resection of an intramedullary ependymoma through a posterior midline myelotomy. The video can be found here: http://youtu.be/lcHhymSvSqU.

[Spinal cord injury due to penetrating missiles].

PubMed

Ohry, Avi

2003-10-01

Gunshot wound of the spine is a major cause of spinal cord injury among US civilian population, members of the military armed conflict personnel, or civilians injured in terrorists attacks. The bullet fragments cause damage to the spinal cord even without penetrating the spinal canal. Concussive effects, heat, fractures or vascular injury may cause the neurological damage. Unfortunately, bullet or shrapnel removal or laminectomy do not change the prognosis. In this article we review the historical background, the Israeli experience, ballistic-forensic considerations, complications, treatment and prognosis.

An ex vivo laser-induced spinal cord injury model to assess mechanisms of axonal degeneration in real-time.

PubMed

Okada, Starlyn L M; Stivers, Nicole S; Stys, Peter K; Stirling, David P

2014-11-25

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 that directly injures axons and secondary injury mechanisms; controlled infusion of reagents directly to the perfusate bathing the cord; precise alterations of the environmental milieu (e.g., calcium, sodium ions, known contributors to axonal injury, but near impossible to manipulate in vivo); and murine models also offer an advantage as they provide an opportunity to visualize and manipulate genetically identified cell populations and subcellular structures. Here, we describe how to isolate and image the living spinal cord from mice to capture dynamics of acute axonal injury.

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

PubMed

Rangasamy, Suresh Babu

2013-07-01

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

A Community Perspective on Bowel Management and Quality of Life after Spinal Cord Injury: The Influence of Autonomic Dysreflexia.

PubMed

Inskip, Jessica A; Lucci, Vera-Ellen M; McGrath, Maureen S; Willms, Rhonda; Claydon, Victoria E

2018-05-01

Autonomic dysfunction is common in individuals with spinal cord injury (SCI) and leads to numerous abnormalities, including profound cardiovascular and bowel dysfunction. In those with high-level lesions, bowel management is a common trigger for autonomic dysreflexia (AD; hypertension provoked by sensory stimuli below the injury level). Improving bowel care is integral for enhancing quality of life (QoL). We aimed to describe the relationships between bowel care, AD, and QoL in individuals with SCI. We performed an online community survey of individuals with SCI. Those with injury at or above T7 were considered at risk for AD. Responses were received from 287 individuals with SCI (injury levels C1-sacral and average duration of injury 17.1 ± 12.9 [standard deviation] years). Survey completion rate was 73% (n = 210). Bowel management was a problem for 78%: it interfered with personal relationships (60%) and prevented staying (62%) and working (41%) away from home. The normal bowel care duration was >60 min in 24% and most used digital rectal stimulation (59%); 33% reported bowel incontinence at least monthly. Of those at risk for AD (n = 163), 74% had AD symptoms during bowel care; 32% described palpitations. AD interfered with activities of daily living in 51%. Longer durations of bowel care (p < 0.001) and more severe AD (p = 0.04) were associated with lower QoL. Bowel management is a key concern for individuals with SCI and is commonly associated with symptoms of AD. Further studies should explore ways to manage bowel dysfunction, increase self-efficacy, and ameliorate the impact of AD to improve QoL.

Development of an Algorithm to Perform a Comprehensive Study of Autonomic Dysreflexia in Animals with High Spinal Cord Injury Using a Telemetry Device.

PubMed

Popok, David; West, Christopher; Frias, Barbara; Krassioukov, Andrei V

2016-07-29

Spinal cord injury (SCI) is a debilitating neurological condition characterized by somatic and autonomic dysfunctions. In particular, SCI above the mid-thoracic level can lead to a potentially life-threatening hypertensive condition called autonomic dysreflexia (AD) that is often triggered by noxious or non-noxious somatic or visceral stimuli below the level of injury. One of the most common triggers of AD is the distension of pelvic viscera, such as during bladder and bowel distension or evacuation. This protocol presents a novel pattern recognition algorithm developed for a JAVA platform software to study the fluctuations of cardiovascular parameters as well as the number, severity and duration of spontaneously occurring AD events. The software is able to apply a pattern recognition algorithm on hemodynamic data such as systolic blood pressure (SBP) and heart rate (HR) extracted from telemetry recordings of conscious and unrestrained animals before and after thoracic (T3) complete transection. With this software, hemodynamic parameters and episodes of AD are able to be detected and analyzed with minimal experimenter bias.

Potential of human dental stem cells in repairing the complete transection of rat spinal cord

NASA Astrophysics Data System (ADS)

Yang, Chao; Li, Xinghan; Sun, Liang; Guo, Weihua; Tian, Weidong

2017-04-01

Objective. The adult spinal cord of mammals contains a certain amount of neural precursor cells, but these endogenous cells have a limited capacity for replacement of lost cells after spinal cord injury. The exogenous stem cells transplantation has become a therapeutic strategy for spinal cord repairing because of their immunomodulatory and differentiation capacity. In addition, dental stem cells originating from the cranial neural crest might be candidate cell sources for neural engineering. Approach. Human dental follicle stem cells (DFSCs), stem cells from apical papilla (SCAPs) and dental pulp stem cells (DPSCs) were isolated and identified in vitro, then green GFP-labeled stem cells with pellets were transplanted into completely transected spinal cord. The functional recovery of rats and multiple neuro-regenerative mechanisms were explored. Main results. The dental stem cells, especially DFSCs, demonstrated the potential in repairing the completely transected spinal cord and promote functional recovery after injury. The major involved mechanisms were speculated below: First, dental stem cells inhibited the expression of interleukin-1β to reduce the inflammatory response; second, they inhibited the expression of ras homolog gene family member A (RhoA) to promote neurite regeneration; third, they inhibited the sulfonylurea receptor1 (SUR-1) expression to reduce progressive hemorrhagic necrosis; lastly, parts of the transplanted cells survived and differentiated into mature neurons and oligodendrocytes but not astrocyte, which is beneficial for promoting axons growth. Significance. Dental stem cells presented remarkable tissue regenerative capability after spinal cord injury through immunomodulatory, differentiation and protection capacity.

High-resolution three-dimensional visualization of the rat spinal cord microvasculature by synchrotron radiation micro-CT

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

Hu, Jianzhong; Cao, Yong; Wu, Tianding

2014-10-15

Purpose: Understanding the three-dimensional (3D) morphology of the spinal cord microvasculature has been limited by the lack of an effective high-resolution imaging technique. In this study, synchrotron radiation microcomputed tomography (SRµCT), a novel imaging technique based on absorption imaging, was evaluated with regard to the detection of the 3D morphology of the rat spinal cord microvasculature. Methods: Ten Sprague-Dawley rats were used in this ex vivo study. After contrast agent perfusion, their spinal cords were isolated and scanned using conventional x-rays, conventional micro-CT (CµCT), and SRµCT. Results: Based on contrast agent perfusion, the microvasculature of the rat spinal cord wasmore » clearly visualized for the first time ex vivo in 3D by means of SRµCT scanning. Compared to conventional imaging techniques, SRµCT achieved higher resolution 3D vascular imaging, with the smallest vessel that could be distinguished approximately 7.4 μm in diameter. Additionally, a 3D pseudocolored image of the spinal cord microvasculature was generated in a single session of SRµCT imaging, which was conducive to detailed observation of the vessel morphology. Conclusions: The results of this study indicated that SRµCT scanning could provide higher resolution images of the vascular network of the spinal cord. This modality also has the potential to serve as a powerful imaging tool for the investigation of morphology changes in the 3D angioarchitecture of the neurovasculature in preclinical research.« less

Scissors stab wound to the cervical spinal cord at the craniocervical junction.

PubMed

Zhang, Xiao-Yong; Yang, Ying-Ming

2016-06-01

Stab wounds resulting in spinal cord injury of the craniocervical junction are rare. A scissors stab wound to the cervical spinal cord has been reported only once in the literature. This paper aimed to report a case of Brown-Séquard-plus syndrome in an 8-year-old boy secondary to a scissors stab wound at the craniocervical junction. Case report and review of the literature. Case report of an 8-year-old boy accidentally stabbed in the neck by scissors, which were thrown as a dart. The case study of an 8-year-old boy who was hospitalized because of a scissors stab wound at the craniocervical junction. The patient developed Brown-Séquard-plus syndrome on the left side of the body. Magnetic resonance imaging revealed a laceration of the spinal cord at the craniocervical junction with cerebrospinal fluid leakage. Careful cleansing and interrupted sutures of the wounds were performed to prevent cerebrospinal fluid leakage. Rehabilitation therapy was performed 2 days later. A follow-up examination revealed complete recovery of the neurologic deficit 8 months post-injury. Treatment of scissors stab wounds to the cervical spinal cord, whether conservative management or thorough surgical exploration, should be individualized based on history, examination, and imaging. As shown in this case report, despite conservative management, complete recovery, which was unexpected, was attributed to the initial mild laceration of the spinal cord and ipsilateral spinal cord functional compensation. Copyright © 2016 Elsevier Inc. All rights reserved.

Cannabis use in persons with traumatic spinal cord injury in Denmark.

PubMed

Andresen, Sven R; Biering-Sørensen, Fin; Hagen, Ellen Merete; Nielsen, Jørgen F; Bach, Flemming W; Finnerup, Nanna B

2017-01-31

To evaluate recreational and medical cannabis use in individuals with traumatic spinal cord injury, including reasons and predictors for use, perceived benefits and negative consequences. Cross-sectional survey in Denmark. A 35-item questionnaire was sent to 1,101 patients with spinal cord injury who had been in contact with a rehabilitation centre between 1990 and 2012. A total of 537 participants completed the questionnaire. Of these, 36% had tried cannabis at least once and 9% were current users. Of current users, 79% had started to use cannabis before their spinal cord injury. The main reason for use was pleasure, but 65% used cannabis partly for spinal cord injury-related consequences and 59% reported at least good effect on pain and spasticity. Negative consequences of use were primarily inertia and feeling quiet/subdued. Lower age, living in rural areas/larger cities, tobacco-smoking, high alcohol intake and higher muscle stiffness were significantly associated with cannabis use. Those who had never tried cannabis reported that they would mainly use cannabis to alleviate pain and spasticity if it were legalized. Cannabis use is more frequent among individuals with spinal cord injury in Denmark than among the general population. High muscle stiffness and various demographic characteristics (lower age, living in rural areas/larger cities, tobacco-smoking and high alcohol intake) were associated with cannabis use. Most participants had started using cannabis before their spinal cord injury. There was considerable overlap between recreational and disability-related use.

International Spinal Cord Injury Core Data Set (version 2.0)-including standardization of reporting.

PubMed

Biering-Sørensen, F; DeVivo, M J; Charlifue, S; Chen, Y; New, P W; Noonan, V; Post, M W M; Vogel, L

2017-08-01

The study design includes expert opinion, feedback, revisions and final consensus. The objective of the study was to present the new knowledge obtained since the International Spinal Cord Injury (SCI) Core Data Set (Version 1.0) published in 2006, and describe the adjustments made in Version 2.0, including standardization of data reporting. International. Comments received from the SCI community were discussed in a working group (WG); suggestions from the WG were reviewed and revisions were made. All suggested revisions were considered, and a final version was circulated for final approval. The International SCI Core Data Set (Version 2.0) consists of 25 variables. Changes made to this version include the deletion of one variable 'Total Days Hospitalized' and addition of two variables 'Date of Rehabilitation Admission' and 'Date of Death.' The variable 'Injury Etiology' was extended with six non-traumatic categories, and corresponding 'Date of Injury' for non-traumatic cases, was defined as the date of first physician visit for symptoms related to spinal cord dysfunction. A category reflecting transgender was added. A response category was added to the variable on utilization of ventilatory assistance to document the use of continuous positive airway pressure for sleep apnea. Other clarifications were made to the text. The reporting of the pediatric SCI population was updated as age groups 0-5, 6-12, 13-14, 15-17 and 18-21. Collection of the core data set should be a basic requirement of all studies of SCI to facilitate accurate descriptions of patient populations and comparison of results across published studies from around the world.

Objective measures of motor dysfunction after compression spinal cord injury in adult rats: correlations with locomotor rating scores.

PubMed

Semler, Joerg; Wellmann, Katharina; Wirth, Felicitas; Stein, Gregor; Angelova, Srebrina; Ashrafi, Mahak; Schempf, Greta; Ankerne, Janina; Ozsoy, Ozlem; Ozsoy, Umut; Schönau, Eckhard; Angelov, Doychin N; Irintchev, Andrey

2011-07-01

Precise assessment of motor deficits after traumatic spinal cord injury (SCI) in rodents is crucial for understanding the mechanisms of functional recovery and testing therapeutic approaches. Here we analyzed the applicability to a rat SCI model of an objective approach, the single-frame motion analysis, created and used for functional analysis in mice. Adult female Wistar rats were subjected to graded compression of the spinal cord. Recovery of locomotion was analyzed using video recordings of beam walking and inclined ladder climbing. Three out of four parameters used in mice appeared suitable: the foot-stepping angle (FSA) and the rump-height index (RHI), measured during beam walking, and for estimating paw placement and body weight support, respectively, and the number of correct ladder steps (CLS), assessing skilled limb movements. These parameters, similar to the Basso, Beattie, and Bresnahan (BBB) locomotor rating scores, correlated with lesion volume and showed significant differences between moderately and severely injured rats at 1-9 weeks after SCI. The beam parameters, but not CLS, correlated well with the BBB scores within ranges of poor and good locomotor abilities. FSA co-varied with RHI only in the severely impaired rats, while RHI and CLS were barely correlated. Our findings suggest that the numerical parameters estimate, as intended by design, predominantly different aspects of locomotion. The use of these objective measures combined with BBB rating provides a time- and cost-efficient opportunity for versatile and reliable functional evaluations in both severely and moderately impaired rats, combining clinical assessment with precise numerical measures.

Mutations in FLVCR1 Cause Posterior Column Ataxia and Retinitis Pigmentosa

PubMed Central

Rajadhyaksha, Anjali M.; Elemento, Olivier; Puffenberger, Erik G.; Schierberl, Kathryn C.; Xiang, Jenny Z.; Putorti, Maria L.; Berciano, José; Poulin, Chantal; Brais, Bernard; Michaelides, Michel; Weleber, Richard G.; Higgins, Joseph J.

2010-01-01

The study of inherited retinal diseases has advanced our knowledge of the cellular and molecular mechanisms involved in sensory neural signaling. Dysfunction of two specific sensory modalities, vision and proprioception, characterizes the phenotype of the rare, autosomal-recessive disorder posterior column ataxia and retinitis pigmentosa (PCARP). Using targeted DNA capture and high-throughput sequencing, we analyzed the entire 4.2 Mb candidate sequence on chromosome 1q32 to find the gene mutated in PCARP in a single family. Employing comprehensive bioinformatic analysis and filtering, we identified a single-nucleotide coding variant in the feline leukemia virus subgroup C cellular receptor 1 (FLVCR1), a gene encoding a heme-transporter protein. Sanger sequencing confirmed the FLVCR1 mutation in this family and identified different homozygous missense mutations located within the protein's transmembrane channel segment in two other unrelated families with PCARP. To determine whether the selective pathologic features of PCARP correlated with FLVCR1 expression, we examined wild-type mouse Flvcr1 mRNA levels in the posterior column of the spinal cord and the retina via quantitative real-time reverse-transcriptase PCR. The Flvcr1 mRNA levels were most abundant in the retina, followed by the posterior column of the spinal cord and other brain regions. These results suggest that aberrant FLVCR1 causes a selective degeneration of a subpopulation of neurons in the retina and the posterior columns of the spinal cord via dysregulation of heme or iron homeostasis. This finding broadens the molecular basis of sensory neural signaling to include common mechanisms that involve proprioception and vision. PMID:21070897

Spinal Cord Diseases

MedlinePlus

... spinal muscular atrophy Symptoms vary but might include pain, numbness, loss of sensation and muscle weakness. These symptoms can occur around the spinal cord, and also in other areas such as your arms and legs. Treatments often include medicines and surgery.

Nonlinear Viscoelastic Characterization of the Porcine Spinal Cord

PubMed Central

Shetye, Snehal; Troyer, Kevin; Streijger, Femke; Lee, Jae H. T.; Kwon, Brian K.; Cripton, Peter; Puttlitz, Christian M.

2014-01-01

Although quasi-static and quasi-linear viscoelastic properties of the spinal cord have been reported previously, there are no published studies that have investigated the fully (strain-dependent) nonlinear viscoelastic properties of the spinal cord. In this study, stress relaxation experiments and dynamic cycling were performed on six fresh porcine lumbar cord specimens to examine their viscoelastic mechanical properties. The stress relaxation data were fitted to a modified superposition formulation and a novel finite ramp time correction technique was applied. The parameters obtained from this fitting methodology were used to predict the average dynamic cyclic viscoelastic behavior of the porcine cord. The data indicate that the porcine spinal cord exhibited fully nonlinear viscoelastic behavior. The average weighted RMSE for a Heaviside ramp fit was 2.8kPa, which was significantly greater (p < 0.001) than that of the nonlinear (comprehensive viscoelastic characterization (CVC) method) fit (0.365kPa). Further, the nonlinear mechanical parameters obtained were able to accurately predict the dynamic behavior, thus exemplifying the reliability of the obtained nonlinear parameters. These parameters will be important for future studies investigating various damage mechanisms of the spinal cord and studies developing high resolution finite elements models of the spine. PMID:24211612

The rat corticospinal system is functionally and anatomically segregated.

PubMed

Olivares-Moreno, Rafael; Moreno-Lopez, Yunuen; Concha, Luis; Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

2017-12-01

The descending corticospinal (CS) projection has been considered a key element for motor control, which results from direct and indirect modulation of spinal cord pre-motor interneurons in the intermediate gray matter of the spinal cord, which, in turn, influences motoneurons in the ventral horn. The CS tract (CST) is also involved in a selective and complex modulation of sensory information in the dorsal horn. However, little is known about the spinal network engaged by the CST and the organization of CS projections that may encode different cortical outputs to the spinal cord. This study addresses the issue of whether the CS system exerts parallel control on different spinal networks, which together participate in sensorimotor integration. Here, we show that in the adult rat, two different and partially intermingled CS neurons in the sensorimotor cortex activate, with different time latencies, distinct spinal cord neurons located in the dorsal horn and intermediate zone of the same segment. The fact that different populations of CS neurons project in a segregated manner suggests that CST is composed of subsystems controlling different spinal cord circuits that modulate motor outputs and sensory inputs in a coordinated manner.

Spinal cord ischemia following thoracotomy without epidural anesthesia.

PubMed

Raz, Aeyal; Avramovich, Aharon; Saraf-Lavi, Efrat; Saute, Milton; Eidelman, Leonid A

2006-06-01

Paraplegia is an uncommon yet devastating complication following thoracotomy, usually caused by compression or ischemia of the spinal cord. Ischemia without compression may be a result of global ischemia, vascular injury and other causes. Epidural anesthesia has been implicated as a major cause. This report highlights the fact that perioperative cord ischemia and paraplegia may be unrelated to epidural intervention. A 71-yr-old woman was admitted for a left upper lobectomy for resection of a non-small cell carcinoma of the lung. The patient refused epidural catheter placement and underwent a left T5-6 thoracotomy under general anesthesia. During surgery, she was hemodynamically stable and good oxygen saturation was maintained. Several hours following surgery the patient complained of loss of sensation in her legs. Neurological examination disclosed a complete motor and sensory block at the T5-6 level. Magnetic resonance imaging (MRI) revealed spinal cord ischemia. The patient received iv steroid treatment, but remained paraplegic. Five months following the surgery there was only partial improvement in her motor symptoms. A follow-up MRI study was consistent with a diagnosis of spinal cord ischemia. In this case of paraplegia following thoracic surgery for lung resection, epidural anesthesia/analgesia was not used. The MRI demonstrated evidence of spinal cord ischemia, and no evidence of cord compression. This case highlights that etiologies other than epidural intervention, such as injury to the spinal segmental arteries during thoracotomy, should be considered as potential causes of cord ischemia and resultant paraplegia in this surgical population.

Psychometric Validation of the World Health Organization Disability Assessment Schedule 2.0-Twelve-Item Version in Persons with Spinal Cord Injuries

ERIC Educational Resources Information Center

Smedema, Susan Miller; Ruiz, Derek; Mohr, Michael J.

2017-01-01

Purpose: To evaluate the factorial and concurrent validity and internal consistency reliability of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) 12-item version in persons with spinal cord injuries. Method: Two hundred forty-seven adults with spinal cord injuries completed an online survey consisting of the WHODAS…

Experiences of Living with Pain after a Spinal Cord Injury

DTIC Science & Technology

2013-09-01

AD_________________ Award Number: W81XWH-12-1-0465 TITLE: Experiences of Living with Pain after a...COVERED 01 September 2012 – 31 August 2013 4. TITLE AND SUBTITLE Experiences of Living with Pain after a Spinal Cord Injury 5a. CONTRACT NUMBER...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Persistent chronic pain is prevalent after a spinal cord injury (SCI), with

Employment among Spinal Cord Injured Patients Living in Turkey: A Cross-Sectional Study

ERIC Educational Resources Information Center

Gunduz, Berrin; Erhan, Belgin; Bardak, Ayse Nur

2010-01-01

The aim of this study was to determine the rate of employment and to establish the factors affecting vocational status in spinal cord injured patients living in Turkey. One hundred and fifty-two traumatic spinal cord injured patients older than 18 years with injury duration of at least 1 year and living in the community were included in the study;…

Cardio Respiratory Adaptations with Long Term Personalized Exercise Program in a T12 Spinal Cord Injured Person

ERIC Educational Resources Information Center

Vasiliadis, Angelo; Christoulas, Kosmas; Evaggelinou, Christina; Vrabas, Ioannis

2009-01-01

The purpose of this study was to investigate the physiological adaptations in cardio respiratory endurance with a personalized exercise program with arm-cranking exercise in a paraplegic person (incomplete T12 spinal cord injury). A 32 year-old man with spinal cord injury (T12) participated in the present study performing 30 minutes arm cranking…

Evaluation of normal appearing spinal cord by diffusion tensor imaging, fiber tracking, fractional anisotropy, and apparent diffusion coefficient measurement in 13 dogs

PubMed Central

2013-01-01

Background Functional magnetic resonance (fMR) imaging offers plenty of new opportunities in the diagnosis of central nervous system diseases. Diffusion tensor imaging (DTI) is a technique sensitive to the random motion of water providing information about tissue architecture. We applied DTI to normal appearing spinal cords of 13 dogs of different breeds and body weights in a 3.0 T magnetic resonance (MR) scanner. The aim was to study fiber tracking (FT) patterns by tractography and the variations of the fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) observed in the spinal cords of dogs with different sizes and at different locations (cervical and thoracolumbar). For that reason we added a DTI sequence to the standard clinical MR protocol. The values of FA and ADC were calculated by means of three regions of interest defined on the cervical or the thoracolumbar spinal cord (ROI 1, 2, and 3). Results The shape of the spinal cord fiber tracts was well illustrated following tractography and the exiting nerve roots could be differentiated from the spinal cord fiber tracts. Routine MR scanning times were extended for 8 to 12 min, depending on the size of the field of view (FOV), the slice thickness, and the size of the interslice gaps. In small breed dogs (< 15 kg body weight) the fibers could be tracked over a length of approximately 10 vertebral bodies with scanning times of about 8 min, whereas in large breed dogs (> 25 kg body weight) the traceable fiber length was about 5 vertebral bodies which took 10 to 12 min scanning time. FA and ADC values showed mean values of 0.447 (FA), and 0.560 × 10-3 mm2/s (ADC), respectively without any differences detected with regard to different dog sizes and spinal cord 45 segments examined. Conclusion FT is suitable for the graphical depiction of the canine spinal cord and the exiting nerve roots. The FA and ADC values offer an objective measure for evaluation of the spinal cord fiber integrity in dogs. PMID:23618404

p53 participates in the protective effects of ischemic post-conditioning against OGD-reperfusion injury in primary cultured spinal cord neurons.

PubMed

Li, Jinquan; Chen, Gong; Gao, Xinjie; Shen, Chao; Zhou, Ping; Wu, Xing; Che, Xiaoming; Xie, Rong

2017-01-18

Spinal cord ischemia-reperfusion (I/R) injury is a severe clinical condition, while the mechanism is still not clarified and the therapeutic approach is limited. Ischemia post-conditioning (PC) has been found to have the protective effects against I/R injury in brain. Recently p53 has been reported to take part in the regulation and protection of I/R injury. We hypothesize that PC has the protective effects in primary cultured spinal cord neurons against ischemia-reperfusion injury, and MDM2-p53 signaling pathway may involve in its protective mechanism. In this study, we used an OGD (oxygen and glucose deprivation)-reperfusion model in primary cultured spinal cord neurons to simulate the I/R injury of spinal cord in vitro, and PC was conducted by 3 cycles of 15min restoration of glucose and oxygen with 15min OGD, followed by 6h fully restoration as reperfusion. Lentiviral vectors were used to knock down MDM2 or over-express p53 genes in primary cultured spinal cord neurons. The results showed that 3 cycles of 15min PC generated the most significant protective effects in primary cultured spinal cord neurons against OGD-reperfusion injury. The levels of MDM2 were decreased while p53, Bax, and cleaved Caspase 3 were increased under OGD-reperfusion condition. PC could significantly reverse the down-regulation of MDM2 and up-regulation of p53, Bax, and cleaved Caspase 3 by OGD-reperfusion injury. Moreover, MDM2 knockdown or p53 over-expression could induce the cleaved Caspase 3 expression and blocked the protective effects of PC in primary cultured spinal cord neurons against OGD-reperfusion injury. In conclusion, our work demonstrated that MDM2-p53 pathway plays a pivotal role in the protective effect of PC against OGD-reperfusion injury and PC may be a feasible therapy strategy in the treatment for spinal cord I/R injury. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2018-02-01

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

Involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters in neonatal rat spinal cord.

PubMed

Suzuki, H; Yoshioka, K; Yanagisawa, M; Urayama, O; Kurihara, T; Hosoki, R; Saito, K; Otsuka, M

1994-09-01

1. The possible involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters was examined in the spinal cord of the neonatal rat. 2. The magnitude of substance P (SP)- or neurokinin A (NKA)-evoked depolarization of a lumbar ventral root in the isolated spinal cord preparation was increased by a mixture of peptidase inhibitors, consisting of actinonin (6 microM), arphamenine B (6 microM), bestatin (10 microM), captopril (10 microM) and thiorphan (0.3 microM). The mixture augmented the response to NKA more markedly than that to SP. 3. In the isolated spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow depolarization of the L3 ventral root was augmented by the mixture of peptidase inhibitors in the presence of naloxone (0.5 microM) but not in the presence of both naloxone and a tachykinin receptor antagonist, GR71251 (5 microM). 4. Application of capsaicin (0.5 microM) for 6 min to the spinal cord evoked an increase in the release of SP from the spinal cord. The amount of SP released was significantly augmented by the mixture of peptidase inhibitors. 5. Synaptic membrane fractions were prepared from neonatal rat spinal cords. These fractions showed degrading activities for SP and NKA and the activities were inhibited by the mixture of peptidase inhibitors. The degrading activity for NKA was higher than that for SP and the inhibitory effect of the mixture for NKA was more marked than that for SP. Although some other fractions obtained from homogenates of spinal cords showed higher degrading activities for SP, these activities were insensitive to the mixture of peptidase inhibitors. 6. Effects of individual peptidase inhibitors on the enzymatic degradation of SP and NKA by synaptic membrane fractions were examined. Thiorphan, actinonin and captopril inhibited SP degradation, while thiorphan and actinonin, but not captopril, inhibited NKA degradation. The potency of the inhibition of each peptidase inhibitor was lower than that of the mixture.7. The present results suggest that enzymatic degradation is involved in the inactivation of tachykinin neurotransmitters in the spinal cord of the neonatal rat.

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

PubMed

Wang, Fangyong; Yuan, Yuan; Li, Jianjun

2015-12-01

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

β-Blockade use for Traumatic Injuries and Immunomodulation: A Review of Proposed Mechanisms and Clinical Evidence.

PubMed

Loftus, Tyler J; Efron, Philip A; Moldawer, Lyle L; Mohr, Alicia M

2016-10-01

Sympathetic nervous system activation and catecholamine release are important events following injury and infection. The nature and timing of different pathophysiologic insults have significant effects on adrenergic pathways, inflammatory mediators, and the host response. Beta adrenergic receptor blockers (β-blockers) are commonly used for treatment of cardiovascular disease, and recent data suggests that the metabolic and immunomodulatory effects of β-blockers can expand their use. β-blocker therapy can reduce sympathetic activation and hypermetabolism as well as modify glucose homeostasis and cytokine expression. It is the purpose of this review to examine either the biologic basis for proposed mechanisms or to describe current available clinical evidence for the use of β-blockers in traumatic brain injury, spinal cord injury, hemorrhagic shock, acute traumatic coagulopathy, erythropoietic dysfunction, metabolic dysfunction, pulmonary dysfunction, burns, immunomodulation, and sepsis.

Calcineurin Dysregulation Underlies Spinal Cord Injury-Induced K+ Channel Dysfunction in DRG Neurons.

PubMed

Zemel, Benjamin M; Muqeem, Tanziyah; Brown, Eric V; Goulão, Miguel; Urban, Mark W; Tymanskyj, Stephen R; Lepore, Angelo C; Covarrubias, Manuel

2017-08-23

Dysfunction of the fast-inactivating Kv3.4 potassium current in dorsal root ganglion (DRG) neurons contributes to the hyperexcitability associated with persistent pain induced by spinal cord injury (SCI). However, the underlying mechanism is not known. In light of our previous work demonstrating modulation of the Kv3.4 channel by phosphorylation, we investigated the role of the phosphatase calcineurin (CaN) using electrophysiological, molecular, and imaging approaches in adult female Sprague Dawley rats. Pharmacological inhibition of CaN in small-diameter DRG neurons slowed repolarization of the somatic action potential (AP) and attenuated the Kv3.4 current. Attenuated Kv3.4 currents also exhibited slowed inactivation. We observed similar effects on the recombinant Kv3.4 channel heterologously expressed in Chinese hamster ovary cells, supporting our findings in DRG neurons. Elucidating the molecular basis of these effects, mutation of four previously characterized serines within the Kv3.4 N-terminal inactivation domain eliminated the effects of CaN inhibition on the Kv3.4 current. SCI similarly induced concurrent Kv3.4 current attenuation and slowing of inactivation. Although there was little change in CaN expression and localization after injury, SCI induced upregulation of the native regulator of CaN 1 (RCAN1) in the DRG at the transcript and protein levels. Consistent with CaN inhibition resulting from RCAN1 upregulation, overexpression of RCAN1 in naive DRG neurons recapitulated the effects of pharmacological CaN inhibition on the Kv3.4 current and the AP. Overall, these results demonstrate a novel regulatory pathway that links CaN, RCAN1, and Kv3.4 in DRG neurons. Dysregulation of this pathway might underlie a peripheral mechanism of pain sensitization induced by SCI. SIGNIFICANCE STATEMENT Pain sensitization associated with spinal cord injury (SCI) involves poorly understood maladaptive modulation of neuronal excitability. Although central mechanisms have received significant attention, recent studies have identified peripheral nerve hyperexcitability as a driver of persistent pain signaling after SCI. However, the ion channels and signaling molecules responsible for this change in primary sensory neuron excitability are still not well defined. To address this problem, this study used complementary electrophysiological and molecular methods to determine how Kv3.4, a voltage-gated K + channel robustly expressed in dorsal root ganglion neurons, becomes dysfunctional upon calcineurin (CaN) inhibition. The results strongly suggest that CaN inhibition underlies SCI-induced dysfunction of Kv3.4 and the associated excitability changes through upregulation of the native regulator of CaN 1 (RCAN1). Copyright © 2017 the authors 0270-6474/17/378257-17$15.00/0.

Early Versus Delayed Surgical Decompression of Spinal Cord after Traumatic Cervical Spinal Cord Injury: A Cost-Utility Analysis.

PubMed

Furlan, Julio C; Craven, B Catharine; Massicotte, Eric M; Fehlings, Michael G

2016-04-01

This cost-utility analysis was undertaken to compare early (≤24 hours since trauma) versus delayed surgical decompression of spinal cord to determine which approach is more cost effective in the management of patients with acute traumatic cervical spinal cord injury (SCI). This study includes the patients enrolled into the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS) and admitted at Toronto Western Hospital. Cases were grouped into patients with motor complete SCI and individuals with motor incomplete SCI. A cost-utility analysis was performed for each group of patients by the use of data for the first 6 months after SCI. The perspective of a public health care insurer was adopted. Costs were estimated in 2014 U.S. dollars. Utilities were estimated from the STASCIS. The baseline analysis indicates early spinal decompression is more cost-effective approach compared with the delayed spinal decompression. When we considered the delayed spinal decompression as the baseline strategy, the incremental cost-effectiveness ratio analysis revealed a saving of US$ 58,368,024.12 per quality-adjusted life years gained for patients with complete SCI and a saving of US$ 536,217.33 per quality-adjusted life years gained in patients with incomplete SCI for the early spinal decompression. The probabilistic analysis confirmed the early-decompression strategy as more cost effective than the delayed-decompression approach, even though there is no clearly dominant strategy. The results of this economic analysis suggests that early decompression of spinal cord was more cost effective than delayed surgical decompression in the management of patients with motor complete and incomplete SCI, even though no strategy was clearly dominant. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-09-01

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