[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.

Evidence that spinal segmental nitric oxide mediates tachyphylaxis to peripheral local anesthetic nerve block.

PubMed

Wang, C; Sholas, M G; Berde, C B; DiCanzio, J; Zurakowski, D; Wilder, R T

2001-09-01

Tachyphylaxis to sciatic nerve blockade in rats correlates with hyperalgesia. Spinal inhibition of nitric oxide synthase with N(G)nitro-L-arginine methyl ester (L-NAME) has been shown to prevent hyperalgesia. Given systemically, L-NAME also prevents tachyphylaxis. The action of L-NAME in preventing tachyphylaxis therefore may be mediated at spinal sites. We compared systemic versus intrathecal potency of L-NAME in modulating tachyphylaxis to sciatic nerve block. Rats were prepared with intrathecal catheters. Three sequential sciatic nerve blocks were placed. Duration of block of thermal nocifensive, proprioceptive and motor responses was recorded. We compared spinal versus systemic dose-response to L-NAME, and examined effects of intrathecal arginine on tachyphylaxis. An additional group of rats underwent testing after T10 spinal cord transection. In these rats duration of sciatic nerve block was assessed by determining the heat-induced flexion withdrawal reflex. L-NAME was 25-fold more potent in preventing tachyphylaxis given intrathecally than intraperitoneally. Intrathecal arginine augmented tachyphylaxis. Spinalized rats exhibited tachyphylaxis to sciatic block. The increased potency of intrathecal versus systemic L-NAME suggests a spinal site of action in inhibiting tachyphylaxis. Descending pathways are not necessary for the development of tachyphylaxis since it occurs even after T10 spinal cord transection. Thus tachyphylaxis, like hyperalgesia, is mediated at least in part by a spinal site of action.

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 ...

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.

[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 classification of growth friendly spine implants.

PubMed

Skaggs, David L; Akbarnia, Behrooz A; Flynn, John M; Myung, Karen S; Sponseller, Paul D; Vitale, Michael G

2014-01-01

Various types of spinal implants have been used with the objective of minimizing spinal deformities while maximizing the spine and thoracic growth in a growing child with a spinal deformity. The aim of this study was to describe a classification system of growth friendly spinal implants to allow researchers and clinicians to have a common language and facilitate comparative studies. Growth friendly spinal implant systems fall into 3 categories based upon the forces of correction the implants exert on the spine, which are as follows: Distraction-based systems correct spinal deformities by mechanically applying a distractive force across a deformed segment with anchors at the top and bottom of the implants, which commonly attach to the spine, rib, and/or the pelvis. The present examples of distraction-based implants are spine-based or rib-based growing rods, vertical expandable titanium rib prosthesis, and remotely expandable devices. Compression-based systems correct spinal deformities with a compressive force applied to the convexity of the curve causing convex growth inhibition. This compressive force may be generated both mechanically at the time of implantation, as well as over time resulting from longitudinal growth of vertebral endplates hindered by the spinal implants. Examples of compression-based systems are vertebral staples and tethers. Guided growth systems correct spinal deformity by anchoring multiple vertebrae (usually including the apical vertebrae) to rods with mechanical forces including translation at the time of the initial implant. The majority of the anchors are not rigidly attached to the rods, thus permitting longitudinal growth over time as the anchors slide over the rods. Examples of guided growth systems include the Luque trolley and Shilla. Each system has its benefits and shortcomings. Knowledge of the fundamental principles upon which these systems are based may aid the clinician to choose an appropriate treatment for patients. Having a common language for these systems may aid in comparative research. Vertical expandable titanium rib prosthesis is used with humanitarian exemption. The other devices mentioned in this manuscript are not approved for growing constructs by the Food and Drug Administration and are used off-label.

In-vivo spinal nerve sensing in MISS using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Chen, Hao; Xu, Weiliang; Broderick, Neil

2016-04-01

In modern Minimally Invasive Spine Surgery (MISS), lack of visualization and haptic feedback information are the main obstacles. The spinal cord is a part of the central nervous system (CNS). It is a continuation of the brain stem, carries motor and sensory messages between CNS and the rest of body, and mediates numerous spinal reflexes. Spinal cord and spinal nerves are of great importance but vulnerable, once injured it may result in severe consequences to patients, e.g. paralysis. Raman Spectroscopy has been proved to be an effective and powerful tool in biological and biomedical applications as it works in a rapid, non-invasive and label-free way. It can provide molecular vibrational features of tissue samples and reflect content and proportion of protein, nucleic acids lipids etc. Due to the distinct chemical compositions spinal nerves have, we proposed that spinal nerves can be identified from other types of tissues by using Raman spectroscopy. Ex vivo experiments were first done on samples taken from swine backbones. Comparative spectral data of swine spinal cord, spinal nerves and adjacent tissues (i.e. membrane layer of the spinal cord, muscle, bone and fatty tissue) are obtained by a Raman micro-spectroscopic system and the peak assignment is done. Then the average spectra of all categories of samples are averaged and normalized to the same scale to see the difference against each other. The results verified the feasibility of spinal cord and spinal nerves identification by using Raman spectroscopy. Besides, a fiber-optic Raman sensing system including a miniature Raman sensor for future study is also introduced. This Raman sensor can be embedded into surgical tools for MISS.

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.;

Protrusion of a rod into the spinal canal 10 years after segmental lumbar spine surgery.

PubMed

Cai, Siyi; Kong, Xiangyi; Yan, Chengrui; Wang, Yipeng; Wan, Xueshuai; Zhang, Jialu; Qiu, Guixing; Yu, Keyi

2017-03-01

The objective of this article is to report an unusual case of a spinal rod that protruded into the spinal canal after lumbar spine surgery.Only 4 cases of spinal rod migration with protrusion into the spinal canal have been reported. This is the first report of a case involving the use of posterior low lumbar segmental instrumentation with a screw-rod system. The left side of the rod gradually migrated and finally protruded into the canal and compressed the cord.A 60-year-old woman presented with pain and numbness of the posterior aspect of the left leg after a long-distance walk. Intermittent claudication became worse, and she developed pain and numbness in the perineal region. An x-ray showed that the left side of a spinal rod among the segmental spinal instruments that had been placed 10 years previously had protruded into the spinal canal.We removed the rod and decompressed the canal at the level of L5-S1. The patient became totally asymptomatic.Rods used as spinal instrumentation have the possibility of protruding into the spinal canal and endangering the nervous system. Long-term follow-up with radiological examinations should be conducted upon completion of spinal operations conducting using instrumentation.

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

PubMed

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

2007-01-15

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

Design and performance test of NIRS-based spinal cord lesion detector

NASA Astrophysics Data System (ADS)

Li, Nanxi; Li, Ting

2018-02-01

Spinal cord lesions can cause a series of severe complications, which can even lead to paralysis with high mortality. However, the traditional diagnosis of spinal cord lesion relies on complicated imaging modalities and other invasive and dangerous methods. Here, we have designed a small monitor based on NIRS technology for noninvasive monitoring for spinal cord lesions. The development of the instrument system includes the design of hardware circuits and the program of software. In terms of hardware, OPT1011 is selected as the light detector, and the appropriate probe distribution structure is selected according to the simulation result of Monte Carlo Simulation. At the same time, the powerful controller is selected as our system's central processing chip for the circuit design, and the data is transmitted by serial port to the host computer for post processing. Finally, we verify the stability and feasibility of the instrument system. It is found that the spinal signal could be obviously detected in the system, which indicates that our monitor based on NIRS technology has the potential to monitor the spinal lesion.

[Virtual clinical diagnosis support system of degenerative stenosis of the lumbar spinal canal].

PubMed

Shevelev, I N; Konovalov, N A; Cherkashov, A M; Molodchenkov, A A; Sharamko, T G; Asiutin, D S; Nazarenko, A G

2013-01-01

The aim of the study was to develop a virtual clinical diagnostic support system of degenerative lumbar spinal stenosis on database of spine registry. Choice of criteria's for diagnostic system was made on symptom analysis of 298 patients with lumbar spinal stenosis. Also was analysed a group of patient with disc herniation's for sensitivity and specify assessment of developed diagnostic support system. Represented clinical diagnostic support system allows identifying patients with degenerative lumbar spinal stenosis on stage of patient's primary visit. System sensitivity and specify are 90 and 71% respectively. "Online" mode of diagnostic system in structure of spine registry provides maximal availability for specialists, regardless of their locations. Development of tools "medicine 2.0" is the actual direction for carrying out further researches with which carrying out the centralized baea collection by means of specialized registers helps.

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

PubMed

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

2018-05-24

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

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.

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

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.

Central nervous system

MedlinePlus

The central nervous system is composed of the brain and spinal cord. Your brain and spinal cord serve as the main "processing center" for your entire nervous system. They control all the workings of your body.

Novel spinal instrumentation to enhance osteogenesis and fusion: a preliminary study.

PubMed

MacEwan, Matthew R; Talcott, Michael R; Moran, Daniel W; Leuthardt, Eric C

2016-09-01

OBJECTIVE Instrumented spinal fusion continues to exhibit high failure rates in patients undergoing multilevel lumbar fusion or pseudarthrosis revision; with Grade II or higher spondylolisthesis; or in those possessing risk factors such as obesity, tobacco use, or metabolic disorders. Direct current (DC) electrical stimulation of bone growth represents a unique surgical adjunct in vertebral fusion procedures, yet existing spinal fusion stimulators are not optimized to enhance interbody fusion. To develop an advanced method of applying DC electrical stimulation to promote interbody fusion, a novel osteogenic spinal system capable of routing DC through rigid instrumentation and into the vertebral bodies was fabricated. A pilot study was designed to assess the feasibility of osteogenic instrumentation and compare the ability of osteogenic instrumentation to promote successful interbody fusion in vivo to standard spinal instrumentation with autograft. METHODS Instrumented, single-level, posterior lumbar interbody fusion (PLIF) with autologous graft was performed at L4-5 in adult Toggenburg/Alpine goats, using both osteogenic spinal instrumentation (plus electrical stimulation) and standard spinal instrumentation (no electrical stimulation). At terminal time points (3 months, 6 months), animals were killed and lumbar spines were explanted for radiographic analysis using a SOMATOM Dual Source Definition CT Scanner and high-resolution Microcat II CT Scanner. Trabecular continuity, radiodensity within the fusion mass, and regional bone formation were examined to determine successful spinal fusion. RESULTS Quantitative analysis of average bone density in pedicle screw beds confirmed that electroactive pedicle screws used in the osteogenic spinal system focally enhanced bone density in instrumented vertebral bodies. Qualitative and quantitative analysis of high-resolution CT scans of explanted lumbar spines further demonstrated that the osteogenic spinal system induced solid bony fusion across the L4-5 disc space as early as 6 weeks postoperatively. In comparison, inactive spinal instrumentation with autograft was unable to promote successful interbody fusion by 6 months postoperatively. CONCLUSIONS Results of this study demonstrate that novel osteogenic spinal instrumentation supports interbody fusion through the focal delivery of DC electrical stimulation. With further technical development and scientific/clinical validation, osteogenic spinal instrumentation may offer a unique alternative to biological scaffolds and pharmaceutical adjuncts used in spinal fusion procedures.

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.

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 ...

A Brain–Spinal Interface Alleviating Gait Deficits after Spinal Cord Injury in Primates

PubMed Central

Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D.; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

2016-01-01

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain–computer interfaces1–3 have directly linked cortical activity to electrical stimulation of muscles, which have restored grasping abilities after hand paralysis1,4. Theoretically, this strategy could also restore control over leg muscle activity for walking5. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges6,7. Recently, we showed in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion8–10. Here, we interfaced leg motor cortex activity with epidural electrical stimulation protocols to establish a brain–spinal interface that alleviated gait deficits after a spinal cord injury in nonhuman primates. Rhesus monkeys were implanted with an intracortical microelectrode array into the leg area of motor cortex; and a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain–spinal interface in intact monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain–spinal interface restored weight-bearing locomotion of the paralyzed leg on a treadmill and overground. The implantable components integrated in the brain–spinal interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury. PMID:27830790

Controlling selective stimulations below a spinal cord hemisection using brain recordings with a neural interface system approach

NASA Astrophysics Data System (ADS)

Panetsos, Fivos; Sanchez-Jimenez, Abel; Torets, Carlos; Largo, Carla; Micera, Silvestro

2011-08-01

In this work we address the use of realtime cortical recordings for the generation of coherent, reliable and robust motor activity in spinal-lesioned animals through selective intraspinal microstimulation (ISMS). The spinal cord of adult rats was hemisectioned and groups of multielectrodes were implanted in both the central nervous system (CNS) and the spinal cord below the lesion level to establish a neural system interface (NSI). To test the reliability of this new NSI connection, highly repeatable neural responses recorded from the CNS were used as a pattern generator of an open-loop control strategy for selective ISMS of the spinal motoneurons. Our experimental procedure avoided the spontaneous non-controlled and non-repeatable neural activity that could have generated spurious ISMS and the consequent undesired muscle contractions. Combinations of complex CNS patterns generated precisely coordinated, reliable and robust motor actions.

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.

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.

Spinal cord stimulation: a review of the safety literature and proposal for perioperative evaluation and management.

PubMed

Walsh, Kevin M; Machado, Andre G; Krishnaney, Ajit A

2015-08-01

There is currently no consensus on appropriate perioperative management of patients with spinal cord stimulator implants. Magnetic resonance imaging (MRI) is considered safe under strict labeling conditions. Electrocautery is generally not recommended in these patients but sometimes used despite known risks. The aim was to discuss the perioperative evaluation and management of patients with spinal cord stimulator implants. A literature review, summary of device labeling, and editorial were performed, regarding the safety of spinal cord stimulator devices in the perioperative setting. A literature review was performed, and the labeling of each Food and Drug Administration (FDA)-approved spinal cord stimulation system was reviewed. The literature review was performed using PubMed and the FDA website (www.fda.gov). Magnetic resonance imaging safety recommendations vary between the models. Certain systems allow for MRI of the brain to be performed, and only one system allows for MRI of the body to be performed, both under strict labeling conditions. Before an MRI is performed, it is imperative to ascertain that the system is intact, without any lead breaks or low impedances, as these can result in heating of the spinal cord stimulation (SCS) and injury to the patient. Monopolar electrocautery is generally not recommended for patients with SCS; however, in some circumstances, it is used when deemed required by the surgeon. When cautery is necessary, bipolar electrocautery is recommended. Modern electrocautery units are to be used with caution as there remains a risk of thermal injury to the tissue in contact with the SCS. As with MRI, electrocautery usage in patients with SCS systems with suspected breaks or abnormal impedances is unsafe and may cause injury to the patient. Spinal cord stimulation is increasingly used in patients with pain of spinal origin, particularly to manage postlaminectomy syndrome. Knowledge of the safety concerns of SCS and appropriate perioperative evaluation and management of the SCS system can reduce risks and improve surgical planning. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

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

Timing of Surgery for Spinal Fractures Associated with Systemic Trauma: A Need for a Strategic and Systemic Approach.

PubMed

Koksal, Ismet; Alagoz, Fatih; Celik, Haydar; Yildirim, Ali Erdem; Akin, Tezcan; Guvenc, Yahya; Karatay, Mete; Erdem, Yavuz

An underestimated evaluation of systemic organs in cases with spinal fractures might jeopardize the intervention for treatment and future complications with an increased morbidity and mortality are almost warranted. In the present study, a retrospective analysis of spinal fracture cases associated with systemic trauma was performed to assess surgical success. A retrospective analysis of patients with thoracolumbar fractures who were admitted to the emergency unit between September 2012 and September 2014 was used for the study. The cases were categorized according to age, sex, reason of trauma, associated trauma, neurological condition and treatment details and results were analysed using SPSS 14.0 for Windows. The most common reason of trauma is detected as falls in 101 cases (64.3%). Radiological evaluation of spinal fractures revealed a compression fracture in 106 cases (67.5%) and other fractures in 51 cases (32.5%). Surgical treatment for spinal fracture was performed in 60.5% of the cases and conservative approach was preferred in 39.5% cases. In non-compressive spinal fractures, an associated pathology like head trauma, lower extremity fracture or neurological deficit was found to be higher in incidence (p < 0.05). Necessity for surgical intervention was found to be more prominent in this group (p < 0.05). However, the fracture type was not found to be associated with morbidity and mortality (p < 0.05). A surgical intervention for a spinal fracture necessitating surgery should rather be performed right after stabilization of the systemic condition which might be associated with decreased morbidity and mortality.

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.

Respiratory Plasticity Following Spinal Injury: Role of Chloride-Dependent Inhibitory Neurotransmission

DTIC Science & Technology

2016-12-01

respiratory pathways following spinal cord injury. J Appl Physiol. 94(2):795-810. Raineteau O and Schwab ME (2001). Plasticity of motor systems after incomplete spinal cord injury. Nat Rev Neurosci. 2(4):262-73. APPENDICES : None

Surgical results of dynamic nonfusion stabilization with the Segmental Spinal Correction System for degenerative lumbar spinal diseases with instability: Minimum 2-year follow-up

PubMed Central

Ohta, Hideki; Matsumoto, Yoshiyuki; Morishita, Yuichirou; Sakai, Tsubasa; Huang, George; Kida, Hirotaka; Takemitsu, Yoshiharu

2011-01-01

Background When spinal fusion is applied to degenerative lumbar spinal disease with instability, adjacent segment disorder will be an issue in the future. However, decompression alone could cause recurrence of spinal canal stenosis because of increased instability on operated segments and lead to revision surgery. Covering the disadvantages of both procedures, we applied nonfusion stabilization with the Segmental Spinal Correction System (Ulrich Medical, Ulm, Germany) and decompression. Methods The surgical results of 52 patients (35 men and 17 women) with a minimum 2-year follow-up were analyzed: 10 patients with lumbar spinal canal stenosis, 15 with lumbar canal stenosis with disc herniation, 20 with degenerative spondylolisthesis, 6 with disc herniation, and 1 with lumbar discopathy. Results The Japanese Orthopaedic Association score was improved, from 14.4 ± 5.3 to 25.5 ± 2.8. The improvement rate was 76%. Range of motion of the operated segments was significantly decreased, from 9.6° ± 4.2° to 2.0° ± 1.8°. Only 1 patient had adjacent segment disease that required revision surgery. There was only 1 screw breakage, but the patient was asymptomatic. Conclusions Over a minimum 2-year follow-up, the results of nonfusion stabilization with the Segmental Spinal Correction System for unstable degenerative lumbar disease were good. It is necessary to follow up the cases with a focus on adjacent segment disorders in the future. PMID:25802671

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

Recent advancements in the SQUID magnetospinogram system

NASA Astrophysics Data System (ADS)

Adachi, Yoshiaki; Kawai, Jun; Haruta, Yasuhiro; Miyamoto, Masakazu; Kawabata, Shigenori; Sekihara, Kensuke; Uehara, Gen

2017-06-01

In this study, a new superconducting quantum interference device (SQUID) biomagnetic measurement system known as magnetospinogram (MSG) is developed. The MSG system is used for observation of a weak magnetic field distribution induced by the neural activity of the spinal cord over the body surface. The current source reconstruction for the observed magnetic field distribution provides noninvasive functional imaging of the spinal cord, which enables medical personnel to diagnose spinal cord diseases more accurately. The MSG system is equipped with a uniquely shaped cryostat and a sensor array of vector-type SQUID gradiometers that are designed to detect the magnetic field from deep sources across a narrow observation area over the body surface of supine subjects. The latest prototype of the MSG system is already applied in clinical studies to develop a diagnosis protocol for spinal cord diseases. Advancements in hardware and software for MSG signal processing and cryogenic components aid in effectively suppressing external magnetic field noise and reducing the cost of liquid helium that act as barriers with respect to the introduction of the MSG system to hospitals. The application of the MSG system is extended to various biomagnetic applications in addition to spinal cord functional imaging given the advantages of the MSG system for investigating deep sources. The study also includes a report on the recent advancements of the SQUID MSG system including its peripheral technologies and wide-spread applications.

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

Respiration and the watershed of spinal CSF flow in humans.

PubMed

Dreha-Kulaczewski, Steffi; Konopka, Mareen; Joseph, Arun A; Kollmeier, Jost; Merboldt, Klaus-Dietmar; Ludwig, Hans-Christoph; Gärtner, Jutta; Frahm, Jens

2018-04-04

The dynamics of human CSF in brain and upper spinal canal are regulated by inspiration and connected to the venous system through associated pressure changes. Upward CSF flow into the head during inspiration counterbalances venous flow out of the brain. Here, we investigated CSF motion along the spinal canal by real-time phase-contrast flow MRI at high spatial and temporal resolution. Results reveal a watershed of spinal CSF dynamics which divides flow behavior at about the level of the heart. While forced inspiration prompts upward surge of CSF flow volumes in the entire spinal canal, ensuing expiration leads to pronounced downward CSF flow, but only in the lower canal. The resulting pattern of net flow volumes during forced respiration yields upward CSF motion in the upper and downward flow in the lower spinal canal. These observations most likely reflect closely coupled CSF and venous systems as both large caval veins and their anastomosing vertebral plexus react to respiration-induced pressure changes.

[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.

Community Care Administration of Spinal Deformities in the Brazilian Public Health System.

PubMed

Bressan-Neto, Mario; da Silva Herrero, Carlos Fernando Pereira; Pacola, Lilian Maria; Nunes, Altacílio Aparecido; Defino, Helton Luiz Aparecido

2017-08-01

Underfunding of the surgical treatment of complex spinal deformities has been an important reason for the steadily growing waiting lists in publicly funded healthcare systems. The aim of this study is to characterize the management of the treatment of spinal deformities in the public healthcare system. A cross-sectional study of 60 patients with complex pediatric spinal deformities waiting for treatment in December 2013 was performed. The evaluated parameters were place of origin, waiting time until first assessment at a specialized spine care center, waiting time for the surgical treatment, and need for implants not reimbursed by the healthcare system. Ninety-one percent of the patients lived in São Paulo State (33% from Ribeirão Preto - DRS XIII). Patients waited for 0.5 to 48.0 months for referral, and the waiting times for surgery ranged from 2 to 117 months. Forty-five percent of the patients required implants for the surgical procedure that were not available. The current management of patients with spinal deformities in the public healthcare system does not provide adequate treatment for these patients in our region. They experience long waiting periods for referral and prolonged waiting times to receive surgical treatment; additionally, many of the necessary procedures are not reimbursed by the public healthcare system.

Spinal injury in car crashes: crash factors and the effects of occupant age.

PubMed

Bilston, Lynne E; Clarke, Elizabeth C; Brown, Julie

2011-08-01

Motor vehicle crashes are the leading cause of serious spinal injury in most developed nations. However, since these injuries are rare, systematic analyses of the crash factors that are predictive of spinal injury have rarely been performed. This study aimed to use a population-reference crash sample to identify crash factors associated with moderate to severe spinal injury, and how these vary with occupant age. The US National Automotive Sampling System Crashworthiness Data System (NASS) data for 1993-2007 were analysed using logistic regression to identify crash factors associated with Abbreviated Injury Scale (AIS)2+ spinal injury among restrained vehicle passengers. Risk of moderate or severe spinal injury (AIS2+) was associated with higher severity crashes (OR=3.5 (95% CI 2.6 to 4.6)), intrusion into an occupant's seating position (OR=2.7 (95% CI 1.9 to 3.7)), striking a fixed object rather than another car (OR=1.7 (95% CI 1.3 to 2.1)), and use of a shoulder-only belt (OR=2.7 (95% CI 1.5 to 4.8)). Older occupants (65 years or older) were at higher risk of spinal injury than younger adults in frontal, side and rollover crashes. Children under 16 were at a lower risk of spinal injury than adults in all crash types except frontal crashes. While the risk of serious spinal injury in motor vehicle crashes is low, these injuries are more common in crashes of higher severity or into fixed objects, and in the presence of intrusion. There are elevated risks of spinal injury for older occupants compared with younger adults, which may reflect changes in biomechanical tolerances with age. Children appear to be at lower risk of serious spinal injury than adults except in frontal crashes.

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.

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

Serotonergic neuron system in the spinal cord of the gar Lepisosteus oculatus (Lepisosteiformes, Osteichthyes) with special regard to the juxtameningeal serotonergic plexus as a paracrine site.

PubMed

Chiba, Akira

2007-02-08

Immunohistochemical and electron microscopic studies were carried out to elucidate the structure of the serotonergic neuron system in the spinal cord of the spotted gar, Lepisosteus oculatus, a nonteleost actinopterygian. Serotonin-immunoreactive (5HT-IR) cell bodies and fibers were widely distributed in the spinal cord, constituting an intrinsic neuron system. This system comprised three anatomical cell groups in different portions of the spinal cord, i.e., the rostromedial cell group, the paired ventrolateral cell groups, and the ventral superficial cell group. The rostromedial cell group included cerebrospinal fluid-contacting neurons with intraventricular processes. The immunostained fibers projecting from all three of these cell groups ran in various directions, mainly ventrally and ventrolaterally, and partly gave rise to a dense plexus at the ventrolateral surface of the spinal cord. Immunoelectron microscopy of the relevant portion demonstrated many varicose fibers containing 5HT-immunopositive vesicles. Conventional electron microscopy of the plexus showed that the constituent varicose fibers were unmyelinated and frequently made a direct contact with the basement membrane contiguous to the leptomeniges (meninx primitiva). There, exocytotic figures of cytoplasmic vesicles were demonstrated, suggesting that 5HT may be secreted, in a paracrine way, into the extraspinal space. This specialized area in the gar spinal cord may be referred to as the juxtameningeal serotonergic plexus.

Computerized lateral endoscopic approach to invertebral bodies

NASA Astrophysics Data System (ADS)

Abbasi, Hamid R.; Hariri, Sanaz; Kim, Daniel; Shahidi, Ramin; Steinberg, Gary

2001-05-01

Spinal surgery is often necessary to ease back pain symptoms. Neuronavigation (NN) allows the surgeon to localize the position of his instruments in 3D using pre- operative CT scans registered to intra-operative marker positions in cranial surgeries. However, this tool is unavailable in spinal surgeries for a variety of reasons. For example, because of the spine's many degrees of freedom and flexibility, the geometric relationship of the skin to the internal spinal anatomy is not fixed. Guided by the currently available imperfect 2D images, it is difficult for the surgeon to correct a patient's spinal anomaly; thus surgical relief of back pain is often only temporary. The Image Guidance Laborator's (IGL) goal is to combine the direct optical control of traditional endoscopy with the 3D orientation of NN. This powerful tool requires registration of the patient's anatomy to the surgical navigation system using internal landmarks rather than skin markers. Pre- operative CT scans matched with intraoperative fluoroscopic images can overcome the problem of spinal movement in NN registration. The combination of endoscopy with fluoroscopic registration of vertebral bodies in a NN system provides a 3D intra-operative navigational system for spinal neurosurgery to visualize the internal surgical environment from any orientation in real time. The accuracy of this system integration is being evaluated by assessing the success of nucleotomies and marker implantations guided by NN-registered endoscopy.

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.

[Serotoninergic system morphofunctional aspects in control of postural and locomotion function].

PubMed

Gerasimenko, Iu P; Moshonkina, T R; Pavlova, N V; Tomilovskaia, E S; Kozlovskaia, I B

2012-12-01

Different mediator systems including serotoninergic one can influence animal's locomotor behavior. It has been shown that the spinal cord in the absence of supraspinal control is able to induce the locomotor activity in hindlimbs and afferent system can activate this mechanism. In behavioral studies on the rats with complete transection of the spinal cord it has been demonstrated that the pharmacological blocking of serotoninergic system results in depression of motor activity mediated by activation of support reactions. Histological studies did not reveal any effects of activation of support reactions on the safety of neurons as well as on the distribution of synaptic contacts within L2-L4 spinal segments. At the same time it has been shown that blockade of the serotoninergic system results in alterations of cells located in 1-3 laminae of dorsal horns, and in 7 Rexed's lamina as well as in redistribution of synaptic contacts in 1-4 Rexed laminae of the spinal cord dorsal horns.

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

PubMed Central

Hook, MA; Grau, JW

2011-01-01

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

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

PubMed

Hultborn, Hans

2003-05-01

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

Leishmania amastigotes in the central nervous system of a naturally infected dog.

PubMed

Márquez, Merce; Pedregosa, José Raúl; López, Jesús; Marco-Salazar, Paola; Fondevila, Dolors; Pumarola, Martí

2013-01-01

A 4-year-old male Labrador Retriever dog was presented with a 10-day history of tetraplegia, depression, and absent postural reflexes. The cerebrospinal fluid was positive for Leishmania spp. DNA. At necropsy, a 2-cm long mass was observed adhered to C(7) and C(8) left spinal nerves. Microscopically, nerve fiber destruction together with mixed inflammatory infiltration was observed in the spinal nerves. Cervical spinal cord sections showed multifocal, diffuse granulomatous inflammation in the white matter. In the brain, perivascular infiltrates were observed in some areas together with subtle pallor of the parenchyma. Immunohistochemistry for Leishmania infantum confirmed the presence of amastigotes in the spinal nerves, spinal cord, brain parenchyma, and choroid plexuses. The current study describes the presence of Leishmania amastigotes in nervous tissue inciting radiculoneuritis, myelitis, and mild meningoencephalitis, suggesting a likely route by which L. infantum amastigotes reach and affect the central nervous system parenchyma.

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

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

PubMed Central

Grau, James W.

2013-01-01

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

21 CFR 888.3070 - Pedicle screw spinal system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... spondylolisthesis with objective evidence of neurologic impairment; fracture; dislocation; scoliosis; kyphosis... with objective evidence of neurologic impairment, fracture, dislocation, scoliosis, kyphosis, spinal...

21 CFR 888.3070 - Pedicle screw spinal system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... spondylolisthesis with objective evidence of neurologic impairment; fracture; dislocation; scoliosis; kyphosis... with objective evidence of neurologic impairment, fracture, dislocation, scoliosis, kyphosis, spinal...

21 CFR 888.3070 - Pedicle screw spinal system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... spondylolisthesis with objective evidence of neurologic impairment; fracture; dislocation; scoliosis; kyphosis... with objective evidence of neurologic impairment, fracture, dislocation, scoliosis, kyphosis, spinal...

Real-time ultrasound-guided spinal anesthesia using the SonixGPS ultrasound guidance system: a feasibility study.

PubMed

Niazi, A U; Chin, K J; Jin, R; Chan, V W

2014-08-01

Real-time ultrasound-guided neuraxial blockade remains a largely experimental technique. SonixGPS® is a new needle tracking system that displays needle tip position on the ultrasound screen. We investigated if this novel technology might aid performance of real-time ultrasound-guided spinal anesthesia. Twenty patients with body mass index < 35 kg/m(2) undergoing elective total joint arthroplasty under spinal anesthesia were recruited. Patients with previous back surgery and spinal abnormalities were excluded. Following a pre-procedural ultrasound scan, a 17G proprietary needle-sensor assembly was inserted in-plane to the transducer in four patients and out-of-plane in 16 patients. In both approaches, the trajectory of insertion was adjusted in real-time until the needle tip lay just superficial to the ligamentum flavum-dura mater complex. At this point, a 25G 120 mm Whitacre spinal needle was inserted through the 17G SonixGPS® needle. Successful dural puncture was confirmed by backflow of cerebrospinal fluid from the spinal needle. An overall success rate of 14/20 (70%) was seen with two failures (50%) and four failures (25%) in the in-plane and out-of-plane groups respectively. Dural puncture was successful on the first skin puncture in 71% of patients and in a single needle pass in 57% of patients. The median total procedure time was 16.4 and 11.1 min in the in-plane and out-of-plane groups respectively. The SonixGPS® system simplifies real-time ultrasound-guided spinal anesthesia to a large extent, especially the out-of-plane approach. Nevertheless, it remains a complex multi-step procedure that requires time, specialized equipment, and a working knowledge of spinal sonoanatomy. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

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

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

Spinal cord evoked magnetic field measurement using a magnetospinography system equipped with a cryocooler.

PubMed

Adachi, Yoshiaki; Oyama, Daisuke; Kawai, Jun; Kawabata, Shigenori; Uehara, Gen

2013-01-01

We have developed a magnetospinography (MSG) system that detects weak magnetic fields associated with spinal cord neural activity using an array of low-temperature superconducting quantum interference device (SQUID)-based magnetic flux sensors. A functional image of the spinal cord can be obtained noninvasively by using this system, and it is effective for precise lesion localization in the diagnosis of spinal cord diseases. The running cost of the developed MSG system mainly depends on liquid helium (LHe) consumption, which is required to maintain the superconducting state of the SQUID sensors. To reduce the LHe consumption, we incorporate a pulse-tube-refrigerator-based cryocooler into the MSG system. Cold gaseous helium is circulated between the cryocooler and the MSG system for cooling the thermal radiation shield of the dewar vessel. Consequently, we achieved a 46% decrease in the LHe consumption rate. Conventional biomagnetic field detection such as magnetoencephalography is often hindered by severe low-frequency band noise from the cryocooler. However, in the case of MSG measurements, such noise can be filtered out because the band of the signal is much higher than that of the cryocooler noise. We demonstrated that the signal-to-noise ratio of the cervical spinal cord evoked magnetic field measurement performed with a working cryocooler is comparable to that of the measurement without a cryocooler.

Real-time advanced spinal surgery via visible patient model and augmented reality system.

PubMed

Wu, Jing-Ren; Wang, Min-Liang; Liu, Kai-Che; Hu, Ming-Hsien; Lee, Pei-Yuan

2014-03-01

This paper presents an advanced augmented reality system for spinal surgery assistance, and develops entry-point guidance prior to vertebroplasty spinal surgery. Based on image-based marker detection and tracking, the proposed camera-projector system superimposes pre-operative 3-D images onto patients. The patients' preoperative 3-D image model is registered by projecting it onto the patient such that the synthetic 3-D model merges with the real patient image, enabling the surgeon to see through the patients' anatomy. The proposed method is much simpler than heavy and computationally challenging navigation systems, and also reduces radiation exposure. The system is experimentally tested on a preoperative 3D model, dummy patient model and animal cadaver model. The feasibility and accuracy of the proposed system is verified on three patients undergoing spinal surgery in the operating theater. The results of these clinical trials are extremely promising, with surgeons reporting favorably on the reduced time of finding a suitable entry point and reduced radiation dose to patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Altered expression of IGF-I system in neurons of the inflamed spinal cord during acute experimental autoimmune encephalomyelitis.

PubMed

Parvaneh Tafreshi, Azita; Talebi, Farideh; Ghorbani, Samira; Bernard, Claude; Noorbakhsh, Farshid

2017-10-01

There is growing evidence that the impaired IGF-I system contributes to neurodegeneration. In this study, we examined the spinal cords of the EAE, the animal model of multiple sclerosis, to see if the expression of the IGF-I system is altered. To induce EAE, C57/BL6 mice were immunized with the Hooke lab MOG kit, sacrificed at the peak of the disease and their spinal cords were examined for the immunoreactivities (ir) of the IGF-I, IGF binding protein-1 (IGFBP-1) and glycogen synthase kinase 3β (GSK3β), as one major downstream molecule in the IGF-I signaling. Although neurons in the non EAE spinal cords did not show the IGF-I immunoreactivity, they were numerously positive for the IGFBP-1. In the inflamed EAE spinal cord however, the patterns of expressions were reversed, that is, a significant increased number of IGF-I expressing neurons versus a reduced number of IGFBP-1 positive neurons. Moreover, while nearly all IGF-I-ir neurons expressed GSK3β, some expressed it more intensely. Considering our previous finding where we showed a significant reduced number of the inactive (phosphorylated) but not that of the total GSK3β expressing neurons in the EAE spinal cord, it is conceivable that the intense total GSK3β expression in the IGF-I-ir neurons belongs to the active form of GSK3β known to exert neuroinflammatory effects. We therefore suggest that the altered expression of the IGF-I system including GSK3β in spinal cord neurons might involve in pathophysiological events during the EAE. © 2017 Wiley Periodicals, Inc.

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.

Proposal of a new radiological classification system for spinal meningiomas as a descriptive tool and surgical guide.

PubMed

Bayoumi, Ahmed B; Laviv, Yosef; Yokus, Burhan; Efe, Ibrahim E; Toktas, Zafer Orkun; Kilic, Turker; Demir, Mustafa K; Konya, Deniz; Kasper, Ekkehard M

2017-11-01

1) To provide neurosurgeons and radiologists with a new quantitative and anatomical method to describe spinal meningiomas (SM) consistently. 2) To provide a guide to the surgical approach needed and amount of bony resection required based on the proposed classification. 3) To report the distribution of our 58 cases of SM over different Stages and Subtypes in correlation to the surgical treatment needed for each case. 4) To briefly review the literature on the rare non-conventional surgical corridors to resect SM. We reviewed the literature to report on previously published cohorts and classifications used to describe the location of the tumor inside the spinal canal. We reviewed the cases that were published prior showing non-conventional surgical approaches to resect spinal meningiomas. We proposed our classification system composed of Staging based on maximal cross-sectional surface area of tumor inside canal, Typing based on number of quadrants occupied by tumor and Subtyping based on location of the tumor bulk to spinal cord. Extradural and extra-spinal growth were also covered by our classification. We then applied it retrospectively on our 58 cases. 12 articles were published illustrating overlapping terms to describe spinal meningiomas. Another 7 articles were published reporting on 23 cases of anteriorly located spinal meningiomas treated with approaches other than laminectomies/laminoplasties. 4 Types, 9 Subtypes and 4 Stages were described in our Classification System. In our series of 58 patients, no midline anterior type was represented. Therefore, all our cases were treated by laminectomies or laminoplasties (with/without facetectomies) except a case with a paraspinal component where a costotransversectomy was needed. Spinal meningiomas can be radiologically described in a precise fashion. Selection of surgical corridor depends mainly on location of tumor bulk inside canal. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of spinal injuries sustained by American service members killed in Iraq and Afghanistan: a study of 2,089 instances of spine trauma.

PubMed

Schoenfeld, Andrew J; Newcomb, Ronald L; Pallis, Mark P; Cleveland, Andrew W; Serrano, Jose A; Bader, Julia O; Waterman, Brian R; Belmont, Philip J

2013-04-01

This study sought to characterize spine injuries among soldiers killed in Iraq or Afghanistan whose autopsy results were stored by the Armed Forces Medical Examiner System. The Armed Forces Medical Examiner System data set was queried to identify American military personnel who sustained a spine injury in conjunction with wounds that resulted in death during deployment in Iraq or Afghanistan from 2003 to 2011. Demographic and injury-specific characteristics were abstracted for each individual identified. The raw incidence of spinal injuries was calculated and correlations were drawn between the presence of spinal trauma and military specialty, mechanism and manner of injury, and wounds in other body regions. Significant associations were also sought for specific injury patterns, including spinal cord injury, atlantooccipital injury, low lumbar vertebral fractures, and lumbosacral dissociation. Statistical calculations were performed using χ statistic, z test, t test with Satterthwaite correction, and multivariate logistic regression. Among 5,424 deceased service members, 2,089 (38.5%) were found to have sustained at least one spinal injury. Sixty-seven percent of all fatalities with spinal injury were caused by explosion, while 15% occurred by gunshot. Spinal fracture was the most common type of injury (n = 2,328), while spinal dislocations occurred in 378, and vertebral column transection occurred in 223. Fifty-two percent sustained at least one cervical spine injury, and spinal cord injury occurred in 40%. Spinal cord injuries were more likely to occur as a result of gunshot (p < 0.001), while atlantooccipital injuries (p < 0.001) and low lumbar fractures (p = 0.01) were significantly higher among combat specialty soldiers. No significant association was identified between spinal injury risk and the periods 2003 to 2007 and 2008 to 2011, although atlantooccipital injuries and spinal cord injury were significantly reduced beginning in 2008 (p < 0.001). The results of this study indicate that the incidence of spinal trauma in modern warfare seems to be higher than previously reported. Epidemiologic study, level III.

Epidemiology and national trends in prevalence and surgical management of metastatic spinal disease.

PubMed

Horn, Samantha R; Dhillon, Ekamjeet S; Poorman, Gregory W; Tishelman, Jared C; Segreto, Frank A; Bortz, Cole A; Moon, John Y; Behery, Omar; Shepard, Nicholas; Diebo, Bassel G; Vira, Shaleen; Passias, Peter G

2018-07-01

Surgical treatment for spinal metastasis has benefited from improvements in surgical techniques. However, the trends in treatment and outcomes for spinal metastasis surgery have not been well-established in a pediatric population. Patients <20 years old with metastatic spinal tumors undergoing spinal surgery were identified in the KID database. Trends for spinal metastases treatment and patient outcomes were analyzed using weight-adjusted ANOVAs. 333 patients were identified in the KID database. The top five primary diagnoses were metastatic brain/spinal cord tumor (19.8%), metastatic nervous system tumor (15.9%), metastatic bone cancer (13.2%), spinal cord tumor (4.2%), and tumor of ventricles (3.0%). There was an increased incidence of spinal metastasis diagnoses from 2003 to 2012 (88.5-117.9 per 100,000; p < 0.001) and an increased trend in the incidence of surgical treatment for spinal metastasis from 2003 to 2012 (p = 0.014). The average age was 10.19 ± 6.33 years old and 38.4% were female. The average length of stay was 17.34 ± 24.36 days. Average CCI increased over time (2003: 7.87 ± 1.40, 2012: 8.44 ± 1.39; p = 0.006). The most common surgeries were excision of spinal cord/meninges lesions (69.1%) and decompression of spinal canal (38.1%). Length of hospital stay and in-hospital mortality did not change over time (17.34-18.04 days, p = 0.337; 1.6%-2.9%, p = 0.801). 10.5% of patients underwent a posterior fusion and 22.2% had at least one complication (nervous system, respiratory, dysphagia, infection). The overall complication rate remained stable over time (23.4%-21.8%, p = 0.952). Surgical treatment for spinal metastasis in the last decade has increased, though the complication rates, in-hospital mortality, and length of stay have remained stable. Copyright © 2018 Elsevier Ltd. All rights reserved.

First-Pass Contrast-Enhanced MRA for Pretherapeutic Diagnosis of Spinal Epidural Arteriovenous Fistulas with Intradural Venous Reflux.

PubMed

Mathur, S; Symons, S P; Huynh, T J; Muthusami, P; Montanera, W; Bharatha, A

2017-01-01

Spinal epidural AVFs are rare spinal vascular malformations. When there is associated intradural venous reflux, they may mimic the more common spinal dural AVFs. Correct diagnosis and localization before conventional angiography is beneficial to facilitate treatment. We hypothesize that first-pass contrast-enhanced MRA can diagnose and localize spinal epidural AVFs with intradural venous reflux and distinguish them from other spinal AVFs. Forty-two consecutive patients with a clinical and/or radiologic suspicion of spinal AVF underwent MR imaging, first-pass contrast-enhanced MRA, and DSA at a single institute (2000-2015). MR imaging/MRA and DSA studies were reviewed by 2 independent blinded observers. DSA was used as the reference standard. On MRA, all 7 spinal epidural AVFs with intradural venous reflux were correctly diagnosed and localized with no interobserver disagreement. The key diagnostic feature was arterialized filling of an epidural venous pouch with a refluxing radicular vein arising from the arterialized epidural venous system. First-pass contrast-enhanced MRA is a reliable and useful technique for the initial diagnosis and localization of spinal epidural AVFs with intradural venous reflux and can distinguish these lesions from other spinal AVFs. © 2017 by American Journal of Neuroradiology.

Neural control of locomotion and training-induced plasticity after spinal and cerebral lesions.

PubMed

Knikou, Maria

2010-10-01

Standing and walking require a plethora of sensorimotor interactions that occur throughout the nervous system. Sensory afferent feedback plays a crucial role in the rhythmical muscle activation pattern, as it affects through spinal reflex circuits the spinal neuronal networks responsible for inducing and maintaining rhythmicity, drives short-term and long-term re-organization of the brain and spinal cord circuits, and contributes to recovery of walking after locomotor training. Therefore, spinal circuits integrating sensory signals are adjustable networks with learning capabilities. In this review, I will synthesize the mechanisms underlying phase-dependent modulation of spinal reflexes in healthy humans as well as those with spinal or cerebral lesions along with findings on afferent regulation of spinal reflexes and central pattern generator in reduced animal preparations. Recovery of walking after locomotor training has been documented in numerous studies but the re-organization of spinal interneuronal and cortical circuits need to be further explored at cellular and physiological levels. For maximizing sensorimotor recovery in people with spinal or cerebral lesions, a multidisciplinary approach (rehabilitation, pharmacology, and electrical stimulation) delivered during various sensorimotor constraints is needed. Copyright 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Sensorimotor Integration by Corticospinal System

PubMed Central

Moreno-López, Yunuen; Olivares-Moreno, Rafael; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

2016-01-01

The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, the CS descending projection plays a major role in motor command, which results from direct and indirect control of spinal cord pre-motor interneurons as well as motoneurons. But in addition, this system is also involved in a selective and complex modulation of sensory feedback. Despite recent evidence confirms that CS projections drive distinct segmental neural circuits that are part of the sensory and pre-motor pathways, little is known about the spinal networks engaged by the corticospinal tract (CST), the organization of CS projections, the intracortical microcircuitry, and the synaptic interactions in the sensorimotor cortex (SMC) that may encode different cortical outputs to the spinal cord. Here is stressed the importance of integrated approaches for the study of sensorimotor function of CS system, in order to understand the functional compartmentalization and hierarchical organization of layer 5 output neurons, who are key elements for motor control and hence, of behavior. PMID:27013985

Sensorimotor Integration by Corticospinal System.

PubMed

Moreno-López, Yunuen; Olivares-Moreno, Rafael; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

2016-01-01

The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, the CS descending projection plays a major role in motor command, which results from direct and indirect control of spinal cord pre-motor interneurons as well as motoneurons. But in addition, this system is also involved in a selective and complex modulation of sensory feedback. Despite recent evidence confirms that CS projections drive distinct segmental neural circuits that are part of the sensory and pre-motor pathways, little is known about the spinal networks engaged by the corticospinal tract (CST), the organization of CS projections, the intracortical microcircuitry, and the synaptic interactions in the sensorimotor cortex (SMC) that may encode different cortical outputs to the spinal cord. Here is stressed the importance of integrated approaches for the study of sensorimotor function of CS system, in order to understand the functional compartmentalization and hierarchical organization of layer 5 output neurons, who are key elements for motor control and hence, of behavior.

Simultaneous submicrometric 3D imaging of the micro-vascular network and the neuronal system in a mouse spinal cord

PubMed Central

Fratini, Michela; Bukreeva, Inna; Campi, Gaetano; Brun, Francesco; Tromba, Giuliana; Modregger, Peter; Bucci, Domenico; Battaglia, Giuseppe; Spanò, Raffaele; Mastrogiacomo, Maddalena; Requardt, Herwig; Giove, Federico; Bravin, Alberto; Cedola, Alessia

2015-01-01

Faults in vascular (VN) and neuronal networks of spinal cord are responsible for serious neurodegenerative pathologies. Because of inadequate investigation tools, the lacking knowledge of the complete fine structure of VN and neuronal system represents a crucial problem. Conventional 2D imaging yields incomplete spatial coverage leading to possible data misinterpretation, whereas standard 3D computed tomography imaging achieves insufficient resolution and contrast. We show that X-ray high-resolution phase-contrast tomography allows the simultaneous visualization of three-dimensional VN and neuronal systems of ex-vivo mouse spinal cord at scales spanning from millimeters to hundreds of nanometers, with nor contrast agent nor sectioning and neither destructive sample-preparation. We image both the 3D distribution of micro-capillary network and the micrometric nerve fibers, axon-bundles and neuron soma. Our approach is very suitable for pre-clinical investigation of neurodegenerative pathologies and spinal-cord-injuries, in particular to resolve the entangled relationship between VN and neuronal system. PMID:25686728

Intravital multiphoton fluorescence imaging and optical manipulation of spinal cord in mice, using a compact fiber laser system.

PubMed

Oshima, Yusuke; Horiuch, Hideki; Honkura, Naoki; Hikita, Atsuhiko; Ogata, Tadanori; Miura, Hiromasa; Imamura, Takeshi

2014-09-01

Near-infrared ultrafast lasers are widely used for multiphoton excited fluorescence microscopy in living animals. Ti:Sapphire lasers are typically used for multiphoton excitation, but their emission wavelength is restricted below 1,000 nm. The aim of this study is to evaluate the performance of a compact Ytterbium-(Yb-) fiber laser at 1,045 nm for multiphoton excited fluorescence microscopy in spinal cord injury. In this study, we employed a custom-designed microscopy system with a compact Yb-fiber laser and evaluated the performance of this system in in vivo imaging of brain cortex and spinal cord in YFP-H transgenic mice. For in vivo imaging of brain cortex, sharp images of basal dendrites, and pyramidal cells expressing EYFP were successfully captured using the Yb-fiber laser in our microscopy system. We also performed in vivo imaging of axon fibers of spinal cord in the transgenic mice. The obtained images were almost as sharp as those obtained using a conventional ultrafast laser system. In addition, laser ablation and multi-color imaging could be performed simultaneously using the Yb-fiber laser. The high-peak pulse Yb-fiber laser is potentially useful for multimodal bioimaging methods based on a multiphoton excited fluorescence microscopy system that incorporates laser ablation techniques. Our results suggest that microscopy systems of this type could be utilized in studies of neuroscience and clinical use in diagnostics and therapeutic tool for spinal cord injury in the future. © 2014 Wiley Periodicals, Inc.

Single-operator real-time ultrasound-guided spinal injection using SonixGPS™: a case series.

PubMed

Brinkmann, Silke; Tang, Raymond; Sawka, Andrew; Vaghadia, Himat

2013-09-01

The SonixGPS™ is a novel needle tracking system that has recently been approved in Canada for ultrasound-guided needle interventions. It allows optimization of needle-beam alignment by providing a real-time display of current and predicted needle tip position. Currently, there is limited evidence on the effectiveness of this technique for performance of real-time spinal anesthesia. This case series reports performance of the SonixGPS system for real-time ultrasound-guided spinal anesthesia in elective patients scheduled for joint arthroplasty. In this single-centre case series, 20 American Society of Anesthesiologists' class I-II patients scheduled for lower limb joint arthroplasty were recruited to undergo real-time ultrasound-guided spinal anesthesia with the SonixGPS after written informed consent. The primary outcome for this clinical cases series was the success rate of spinal anesthesia, and the main secondary outcome was time required to perform spinal anesthesia. Successful spinal anesthesia for joint arthroplasty was achieved in 18/20 patients, and 17 of these required only a single skin puncture. In 7/20 (35%) patients, dural puncture was achieved on the first needle pass, and in 11/20 (55%) patients, dural puncture was achieved with two or three needle redirections. Median (range) time taken to perform the block was 8 (5-14) min. The study procedure was aborted in two cases because our clinical protocol dictated using a standard approach if spinal anesthesia was unsuccessful after three ultrasound-guided insertion attempts. These two cases were classified as failures. No complications, including paresthesia, were observed during the procedure. All patients with successful spinal anesthesia found the technique acceptable and were willing to undergo a repeat procedure if deemed necessary. This case series shows that real-time ultrasound-guided spinal anesthesia with the SonixGPS system is possible within an acceptable time frame. It proved effective with a low rate of failure and a low rate of complications. Our clinical experience suggests that a randomized trial is warranted to compare the SonixGPS with a standard block technique.

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.

Cortex-dependent recovery of unassisted hindlimb locomotion after complete spinal cord injury in adult rats

PubMed Central

Manohar, Anitha; Foffani, Guglielmo; Ganzer, Patrick D; Bethea, John R; Moxon, Karen A

2017-01-01

After paralyzing spinal cord injury the adult nervous system has little ability to ‘heal’ spinal connections, and it is assumed to be unable to develop extra-spinal recovery strategies to bypass the lesion. We challenge this assumption, showing that completely spinalized adult rats can recover unassisted hindlimb weight support and locomotion without explicit spinal transmission of motor commands through the lesion. This is achieved with combinations of pharmacological and physical therapies that maximize cortical reorganization, inducing an expansion of trunk motor cortex and forepaw sensory cortex into the deafferented hindlimb cortex, associated with sprouting of corticospinal axons. Lesioning the reorganized cortex reverses the recovery. Adult rats can thus develop a novel cortical sensorimotor circuit that bypasses the lesion, probably through biomechanical coupling, to partly recover unassisted hindlimb locomotion after complete spinal cord injury. DOI: http://dx.doi.org/10.7554/eLife.23532.001 PMID:28661400

Ergonomics intervention on an alternative design of a spinal board.

PubMed

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

2017-09-01

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

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.

Agreement between Fiber Optic and Optoelectronic Systems for Quantifying Sagittal Plane Spinal Curvature in Sitting

PubMed Central

Cloud, Beth A.; Zhao, Kristin D.; Breighner, Ryan; Giambini, Hugo; An, Kai-Nan

2014-01-01

Spinal posture affects how individuals function from a manual wheelchair. There is a need to directly quantify spinal posture in this population to ultimately improve function. A fiber optic system, comprised of an attached series of sensors, is promising for measuring large regions of the spine in individuals sitting in a wheelchair. The purpose of this study was to determine the agreement between fiber optic and optoelectronic systems for measuring spinal curvature, and describe the range of sagittal plane spinal curvatures in natural sitting. Able-bodied adults (n=26, 13 male) participated. Each participant assumed three sitting postures: natural, slouched (accentuated kyphosis), and extension (accentuated lordosis) sitting. Fiber optic (ShapeTape) and optoelectronic (Optotrak) systems were applied to the skin over spinous processes from S1 to C7 and used to measure sagittal plane spinal curvature. Regions of kyphosis and lordosis were identified. A Cobb angle-like method was used to quantify lordosis and kyphosis. Generalized linear model and Bland-Altman analyses were used to assess agreement. A strong correlation exists between curvature values obtained with Optotrak and ShapeTape (R2=0.98). The mean difference between Optotrak and ShapeTape for kyphosis in natural, extension, and slouched postures was 4.30° (95%LOA: −3.43-12.04°), 3.64° (95%LOA: −1.07-8.36°), and 4.02° (95%LOA: −2.80-10.84°), respectively. The mean difference for lordosis, when present, in natural and extension postures is 2.86° (95%LOA: −1.18-6.90°) and 2.55° (95%LOA: −3.38-8.48°), respectively. In natural sitting, the mean±SD of kyphosis values was 35.07± 6.75°. Lordosis was detected in 8/26 participants: 11.72±7.32°. The fiber optic and optoelectronic systems demonstrate acceptable agreement for measuring sagittal plane thoracolumbar spinal curvature. PMID:24909579

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.

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.

Antinociception by systemically-administered acetaminophen (paracetamol) involves spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors.

PubMed

Liu, Jean; Reid, Allison R; Sawynok, Jana

2013-03-01

Acetaminophen (paracetamol) is a widely used analgesic, but its sites and mechanisms of action remain incompletely understood. Recent studies have separately implicated spinal adenosine A(1) receptors (A(1)Rs) and serotonin 5-HT(7) receptors (5-HT(7)Rs) in the antinociceptive effects of systemically administered acetaminophen. In the present study, we determined whether these two actions are linked by delivering a selective 5-HT(7)R antagonist to the spinal cord of mice and examining nociception using the formalin 2% model. In normal and A(1)R wild type mice, antinociception by systemic (i.p.) acetaminophen 300mg/kg was reduced by intrathecal (i.t.) delivery of the selective 5-HT(7)R antagonist SB269970 3μg. In mice lacking A(1)Rs, i.t. SB269970 did not reverse antinociception by systemic acetaminophen, indicating a link between spinal 5-HT(7)R and A(1)R mechanisms. We also explored potential roles of peripheral A(1)Rs in antinociception by acetaminophen administered both locally and systemically. In normal mice, intraplantar (i.pl.) acetaminophen 200μg produced antinociception in the formalin test, and this was blocked by co-administration of the selective A(1)R antagonist DPCPX 4.5μg. Acetaminophen administered into the contralateral hindpaw had no effect, indicating a local peripheral action. When acetaminophen was administered systemically, its antinociceptive effect was reversed by i.pl. DPCPX in normal mice; this was also observed in A(1)R wild type mice, but not in those lacking A(1)Rs. In summary, we demonstrate a link between spinal 5-HT(7)Rs and A(1)Rs in the spinal cord relevant to antinociception by systemic acetaminophen. Furthermore, we implicate peripheral A(1)Rs in the antinociceptive effects of locally- and systemically-administered acetaminophen. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Quantitative aspects of the clinical performance of transverse tripolar spinal cord stimulation.

PubMed

Wesselink, W A; Holsheimer, J; King, G W; Torgerson, N A; Boom, H B

1999-01-01

A multicenter study was initiated to evaluate the performance of the transverse tripolar system for spinal cord stimulation. Computer modeling had predicted steering of paresthesia with a dual channel stimulator to be the main benefit of the system. The quantitative analysis presented here includes the results of 484 tests in 30 patients. For each test, paresthesia coverage as a function of voltage levels was stored in a computerized database, including a body map which enabled calculation of the degree of paresthesia coverage of separate body areas, as well as the overlap with the painful areas. The results show that with the transverse tripolar system steering of the paresthesia is possible, although optimal steering requires proper placement of the electrode with respect to the spinal cord. Therefore, with this steering ability as well as a larger therapeutic stimulation window as compared to conventional systems, we expect an increase of the long-term efficacy of spinal cord stimulation. Moreover, in view of the stimulation-induced paresthesia patterns, the system allows selective stimulation of the medial dorsal columns.

Intraoperative monitoring of somatosensory-evoked potential in the spinal cord rectification operation by means of wavelet analysis

NASA Astrophysics Data System (ADS)

Liu, W.; Du, M. H.; Chan, Francis H. Y.; Lam, F. K.; Luk, D. K.; Hu, Y.; Fung, Kan S. M.; Qiu, W.

1998-09-01

Recently there has been a considerable interest in the use of a somatosensory evoked potential (SEP) for monitoring the functional integrity of the spinal cord during surgery such as spinal scoliosis. This paper describes a monitoring system and signal processing algorithms, which consists of 50 Hz mains filtering and a wavelet signal analyzer. Our system allows fast detection of changes in SEP peak latency, amplitude and signal waveform, which are the main parameters of interest during intra-operative procedures.

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.

Interaction of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and opioid receptors in spinal cord nociceptive reflexes.

PubMed

Ramos-Zepeda, Guillermo; Herrero, Juan F

2013-08-14

We previously observed that the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) is a very effective antinociceptive agent on intact but not on spinalized adult rats with inflammation. Since a close connection between opioid and adenosine A1 receptors has been described, we studied a possible relationship between these systems in the spinal cord. CPA-mediated antinociception was challenged by the selective adenosine A1 receptor antagonist 8-cyclopentyl-1, 3-dimethylxanthine (CPT) and by the opioid receptor antagonist naloxone on male adult Wistar rats with carrageenan-induced inflammation. Withdrawal reflexes activated by noxious mechanical and electrical stimulation were recorded using the single motor technique in intact and sham-spinalized animals. CPA was very effective in intact and sham spinalized rats but not in spinalized animals. Full reversal of CPA antinociception was observed with i.v. 1mg/kg of naloxone but not with 20mg/kg of CPT i.v. in responses to noxious mechanical and electrical stimulation. CPT fully prevented CPA from any antinociceptive action whereas naloxone did not modify CPA activity. These results suggest a centrally-mediated action, since CPA depressed the wind-up phenomenon which is derived of the activity of spinal cord neurons. The present study provides strong in vivo evidence of an antinociceptive activity mediated by the adenosine A1 receptor system in the spinal cord, linked to an activation of opioid receptors in adult animals with inflammation. © 2013.

LPS-induced knee-joint reactive arthritis and spinal cord glial activation were reduced after intrathecal thalidomide injection in rats.

PubMed

Bressan, Elisângela; Mitkovski, Mišo; Tonussi, Carlos Rogério

2010-10-09

Thalidomide is thought to prevent TNF-α production, and such mechanism could be useful in a spinally delivered drug approach for the control of peripheral inflammation. This study aimed to evaluate the effect of intrathecal thalidomide, in comparison with that of intraperitoneal treatment, on articular incapacitation, edema, synovial leukocyte content, and spinal cord glial activation in a model of Escherichia coli lipopolysaccharide (LPS)-induced reactive arthritis in rats. LPS (30ng) was injected into a knee-joint previously primed with carrageenan (300μg). Systemic (30 and 100mg/kg; intraperitoneal, i.p.) and intrathecal (10 and 100μg; i.t.) thalidomide were given 1h or 20min before LPS injection, respectively. Articular incapacitation and edema were evaluated hourly. After 6h, synovial fluid and lumbar spinal cords were collected for subsequent evaluations of cell migration and expression of CD11b/c and GFAP markers, respectively. Systemic (30 and 100mg/kg) or intrathecal (10 and 100μg) thalidomide reduced articular incapacitation, edema, and polymorphonuclear migration. In addition, i.p. and i.t. thalidomide reduced the expression of CD11b/c and GFAP markers in the lumbar spinal cord. These results suggest that thalidomide can also produce peripheral anti-inflammatory effects through action in the spinal cord that may involve glia inhibition. This study provides new evidence that the direct spinal delivery of immunomodulators may be an alternative for the treatment of arthritic diseases, which require long systemic treatment with drugs associated with undesirable side effects. Copyright © 2010 Elsevier Inc. All rights reserved.

Sustained delivery of bioactive neurotrophin-3 to the injured spinal cord.

PubMed

Elliott Donaghue, Irja; Tator, Charles H; Shoichet, Molly S

2015-01-01

Spinal cord injury is a debilitating condition that currently lacks effective clinical treatment. Neurotrophin-3 (NT-3) has been demonstrated in experimental animal models to induce axonal regeneration and functional improvements, yet its local delivery remains challenging. For ultimate clinical translation, a drug delivery system is required for localized, sustained, and minimally invasive release. Here, an injectable composite drug delivery system (DDS) composed of biodegradable polymeric nanoparticles dispersed in a hyaluronan/methyl cellulose hydrogel was injected into the intrathecal space to achieve acute local delivery to the spinal cord after a thoracic clip compression injury. NT-3 was encapsulated in the DDS and released in vitro for up to 50 d. With a single injection of the DDS into the intrathecal space of the injured spinal cord, NT-3 diffused ventrally through the cord and was detectable in the spinal cord for at least 28 d therein. Delivery of NT-3 resulted in significant axon growth with no effect on the astroglial response to injury in comparison with vehicle and injury controls. NT-3 treatment promoted functional improvements at 21 d according to the Basso Beattie Bresnahan locomotor scale in comparison with the DDS alone. The sustained delivery of bioactive NT-3 to the injured spinal cord achieved in this study demonstrates the promise of this DDS for central nervous system repair.

Robot-Assisted Transoral Odontoidectomy : Experiment in New Minimally Invasive Technology, a Cadaveric Study

PubMed Central

Yang, Moon Sul; Yoon, Tae Ho; Yoon, Do Heum; Kim, Keung Nyun; Pennant, William

2011-01-01

Objective In the field of spinal surgery, a few laboratory results or clinical cases about robotic spinal surgery have been reported. In vivo trials and development of related surgical instruments for spinal surgery are required before its clinical application. We investigated the use of the da Vinci® Surgical System in spinal surgery at the craniovertebral junction in a human cadaver to demonstrate the efficacy and pitfalls of robotic surgery. Methods Dissection of pharyngeal wall to the exposure of C1 and odontoid process was performed with full robotic procedure. Although assistance of another surgeon was necessary for drilling and removal of odontoid process due to the lack of appropriate end-effectors, successful robotic procedures for dural sutures and exposing spinal cord proved its safety and dexterity. Results Robot-assisted odontoidectomy was successfully performed in a human cadaver using the da Vinci® Surgical System with few robotic arm collisions and minimal soft tissue damages. Da Vinci® Surgical System manifested more dexterous movement than human hands in the deep and narrow oral cavity. Furthermore, sutures with robotic procedure in the oral cavity demonstrated the advantage over conventional procedure. Conclusion Presenting cadaveric study proved the probability of robot-assisted transoral approach. However, the development of robotic instruments specific to spinal surgery must first precede its clinical application. PMID:21607188

Involvement of melatonin metabolites in the long-term inhibitory effect of the hormone on rat spinal nociceptive transmission.

PubMed

Mondaca, Mauricio; Hernández, Alejandro; Valladares, Luis; Sierralta, Walter; Noseda, Rodrigo; Soto-Moyano, Rubén

2004-02-01

There is evidence that melatonin and its metabolites could bind to nuclear sites in neurones, suggesting that this hormone is able to exert long-term functional effects in the central nervous system via genomic mechanisms. This study was designed to investigate (i) whether systemically administered melatonin can exert long-term effects on spinal cord windup activity, and (ii) whether blockade of melatonin degradation with eserine could prevent this effect. Rats receiving melatonin (10 mg/kg ip), the same dose of melatonin plus eserine (0.5 mg/kg ip), or saline were studied. Seven days after administration of the drugs or saline, spinal windup of rats was assessed in a C-fiber reflex response paradigm. Results show that rats receiving melatonin exhibited a reduction in spinal windup activity. This was not observed in the animals receiving melatonin plus eserine or saline, suggesting a role for melatonin metabolites in long-term changes of nociceptive transmission in the rat spinal cord.

Contraindications to Athletic Participation. Spinal, Systemic, Dermatologic, Paired-Organ, and Other Issues.

ERIC Educational Resources Information Center

Moeller, James L.

1996-01-01

The second of a two-part series on contraindications to athletic activity, this article examines the sensory, spinal, gastrointestinal, systemic, hematologic, and dermatologic conditions that warrant activity disqualification and provides guidelines about when it is safe to participate. Activity considerations for individuals who have lost a…

Breast Cancer Following Spinal Irradiation for a Childhood Cancer: A Report from the Childhood Cancer Survivor Study

PubMed Central

Moskowitz, Chaya S.; Malhotra, Jyoti; Chou, Joanne F.; Wolden, Suzanne L.; Weathers, Rita E.; Stovall, Marilyn; Armstrong, Gregory T.; Leisenring, Wendy M.; Neglia, Joseph P.; Robison, Leslie L.; Oeffinger, Kevin C.

2015-01-01

Summary It has been suggested that pediatric patients treated with spinal irradiation may have an elevated risk of breast cancer. Among a cohort of 363 long-term survivors of a pediatric central nervous system tumor or leukemia treated with spinal irradiation, there was little evidence of an increased breast cancer risk. PMID:26391961

Does trans‐spinal and local DC polarization affect presynaptic inhibition and post‐activation depression?

PubMed Central

Kaczmarek, D.; Ristikankare, J.

2017-01-01

Key points Trans‐spinal polarization was recently introduced as a means to improve deficient spinal functions. However, only a few attempts have been made to examine the mechanisms underlying DC actions. We have now examined the effects of DC on two spinal modulatory systems, presynaptic inhibition and post‐activation depression, considering whether they might weaken exaggerated spinal reflexes and enhance excessively weakened ones.Direct current effects were evoked by using local intraspinal DC application (0.3–0.4 μA) in deeply anaesthetized rats and were compared with the effects of trans‐spinal polarization (0.8–1.0 mA).Effects of local intraspinal DC were found to be polarity dependent, as locally applied cathodal polarization enhanced presynaptic inhibition and post‐activation depression, whereas anodal polarization weakened them. In contrast, both cathodal and anodal trans‐spinal polarization facilitated them.The results suggest some common DC‐sensitive mechanisms of presynaptic inhibition and post‐activation depression, because both were facilitated or depressed by DC in parallel. Abstract Direct current (DC) polarization has been demonstrated to alleviate the effects of various deficits in the operation of the central nervous system. However, the effects of trans‐spinal DC stimulation (tsDCS) have been investigated less extensively than the effects of transcranial DC stimulation, and their cellular mechanisms have not been elucidated. The main objectives of this study were, therefore, to extend our previous analysis of DC effects on the excitability of primary afferents and synaptic transmission by examining the effects of DC on two spinal modulatory feedback systems, presynaptic inhibition and post‐activation depression, in an anaesthetized rat preparation. Other objectives were to compare the effects of locally and trans‐spinally applied DC (locDC and tsDCS). Local polarization at the sites of terminal branching of afferent fibres was found to induce polarity‐dependent actions on presynaptic inhibition and post‐activation depression, as cathodal locDC enhanced them and anodal locDC depressed them. In contrast, tsDCS modulated presynaptic inhibition and post‐activation depression in a polarity‐independent fashion because both cathodal and anodal tsDCS facilitated them. The results show that the local presynaptic actions of DC might counteract both excessively strong and excessively weak monosynaptic actions of group Ia and cutaneous afferents. However, they indicate that trans‐spinally applied DC might counteract the exaggerated spinal reflexes but have an adverse effect on pathologically weakened spinal activity by additional presynaptic weakening. The results are also relevant for the analysis of the basic properties of presynaptic inhibition and post‐activation depression because they indicate that some common DC‐sensitive mechanisms contribute to them. PMID:27891626

Paralysis recovery in humans and model systems

NASA Technical Reports Server (NTRS)

Edgerton, V. Reggie; Roy, Roland R.

2002-01-01

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

Spinal Accessory Motor Neurons in the Mouse: A Special Type of Branchial Motor Neuron?

PubMed

Watson, Charles; Tvrdik, Petr

2018-04-16

The spinal accessory nerve arises from motor neurons in the upper cervical spinal cord. The axons of these motor neurons exit dorsal to the ligamentum denticulatum and form the spinal accessory nerve. The nerve ascends in the spinal subarachnoid space to enter the posterior cranial fossa through the foramen magnum. The spinal accessory nerve then turns caudally to exit through the jugular foramen alongside the vagus and glossopharyngeal nerves, and then travels to supply the sternomastoid and trapezius muscles in the neck. The unusual course of the spinal accessory nerve has long prompted speculation that it is not a typical spinal motor nerve and that it might represent a caudal remnant of the branchial motor system. Our cell lineage tracing data, combined with images from public databases, show that the spinal accessory motor neurons in the mouse transiently express Phox2b, a transcription factor that is required for development of brain stem branchial motor nuclei. While this is strong prima facie evidence that the spinal accessory motor neurons should be classified as branchial motor, the evolutionary history of these motor neurons in anamniote vertebrates suggests that they may be considered to be an atypical branchial group that possesses both branchial and somatic characteristics. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Transverse Myelitis

MedlinePlus

... can affect the spinal cord, such as sarcoidosis, systemic lupus erythematosus, Sjogren’s syndrome, mixed connective tissue disease, ... on strategies to repair demyelinated spinal cords, including approaches using cell transplantation. This research may lead to ...

Safety of intraoperative electrophysiological monitoring (TES and EMG) for spinal and cranial lesions.

PubMed

Gazzeri, Roberto; Faiola, Andrea; Neroni, Massimiliano; Fiore, Claudio; Callovini, Giorgio; Pischedda, Mauro; Galarza, Marcelo

2013-09-01

Intraoperative motor evoked potentials (MEP) and electromyography (EMG) monitoring in patients with spinal and cranial lesions is a valuable tool for prevention of postoperative motor deficits. The purpose of this study was to determine whether electrophysiological monitoring during skull base, spinal cord, and spinal surgery might be useful for predicting postoperative motor deterioration. From January 2012 to March 2013, thirty-three consecutive patients were studied using intraoperative monitoring (Nuvasive NV-M5 System) to check the integrity of brainstem, spinal cord, and nerve roots, recording transcranial motor evoked potentials (TcMEPs) and electromyography. Changes in MEPs and EMGs were related to postoperative deficits. Preoperative diagnosis included skull base and brainstem lesions (6 patients), spinal tumors (11 patients), spinal deformity (16 cases). Using TcMEPs and EMG is a practicable and safe method. MEPs are useful in any surgery in which the brainstem and spinal cord are at risk. EMG stimulation helps to identify an optimal trans-psoas entry point for an extreme lateral lumbar interbody fusion (XLIF) approach to protect against potential nerve injury. This neural navigation technique via a surgeon-interpreted interface assists the surgical team in safely removing lesions and accessing the intervertebral disc space for minimally invasive spinal procedures.

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.

The process of confrontation with disability in patients with spinal cord injury

PubMed Central

Ahmadzadeh, Gholamhossein; Kouchaki, Anahita; Malekian, Azadeh; Aminorro’aya, Mahin; Boroujeni, Ali Zargham

2010-01-01

BACKGROUND: Spinal injury can establish severe psychological outcomes for the patient and his/her family which requires high adjustment. Health system staff would be able to play their roles well in caring these patients provided with knowing what steps spinal injured people should pass to handle their disability and also what assistance they need in what stages from what sources. This study aimed to explain the process of confrontation with disability in spinal cord injured patients. METHODS: This was a qualitative study with grounded theory approach which was performed in Strauss and Corbin proposed method on twenty people with spinal cord injury who had past at least three months from their spinal injury. Sampling was done in purposive and theoretical method, and analysis of the results was also performed during constant comparative process. RESULTS: Central concept in the data was support which was associated with other concepts and affected them. The patients, with the help of internal and external support could overcome their main problem that was disability feeling and dependency on others and find a new definition for the self, and ultimately achieve the sense of independence and autonomy. CONCLUSIONS: Knowing the process of confrontation with disability along with better understanding of spinal cord injured people would help health system staff to actualize and support their potentials much better through strengthening internal resources and providing appropriate supportive services of each individual. PMID:22069411

Intrathecal Drug Delivery and Spinal Cord Stimulation for the Treatment of Cancer Pain.

PubMed

Xing, Fangfang; Yong, R Jason; Kaye, Alan David; Urman, Richard D

2018-02-05

The purpose of the present investigation is to summarize the body and quality of evidence including the most recent studies in support of intrathecal drug delivery systems and spinal cord stimulation for the treatment of cancer-related pain. In the past 3 years, a number of prospective studies have been published supporting intrathecal drug delivery systems for cancer pain. Additional investigation with adjuvants to morphine-based analgesia including dexmedetomidine and ziconotide support drug-induced benefits of patient-controlled intrathecal analgesia. A study has also been recently published regarding cost-savings for intrathecal drug delivery system compared to pharmacologic management, but an analysis in the Ontario, Canada healthcare system projects additional financial costs. Finally, the Polyanalgesic Consensus Committee has updated its recommendations regarding clinical guidelines for intrathecal drug delivery systems to include new information on dosing, trialing, safety, and systemic opioid reduction. There is still a paucity of clinical evidence for spinal cord stimulation in the treatment of cancer pain. There are new intrathecal drugs under investigation including various conopeptides and AYX1. Large, prospective, modern, randomized controlled studies are still needed to support the use of both intrathecal drug delivery systems as well as spinal cord stimulation for cancer pain populations. There are multiple prospective and small randomized controlled studies that highlight a potential promising future for these interventional modalities. Related to the challenge and urgency of cancer pain, the pain practitioner community is moving toward a multimodal approach that includes discussions regarding the role of intrathecal therapies and spinal cord stimulation to the individualized treatment of patients.

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

Spinal Muscular Atrophy (SMA)

MedlinePlus

... kids of the same age or have trouble lifting things. Kids with SMA can develop scoliosis (a ... Nervous System Your Muscles Wheelchairs Scoliosis Steven's Story: Power Player Kyphosis Muscular Dystrophy Spinal Muscular Atrophy: Steven's ...

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.

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

Systemic and Topical Use of Tranexamic Acid in Spinal Surgery: A Systematic Review

PubMed Central

Winter, Sebastian F.; Santaguida, Carlo; Wong, Jean; Fehlings, Michael G.

2015-01-01

Study Design Combination of narrative and systematic literature reviews. Objectives Massive perioperative blood loss in complex spinal surgery often requires blood transfusions and can negatively affect patient outcome. Systemic use of the antifibrinolytic agent tranexamic acid (TXA) has become widely used in the management of surgical bleeding. We review the clinical evidence for the use of intravenous TXA as a hemostatic agent in spinal surgery and discuss the emerging role for its complementary use as a topical agent to reduce perioperative blood loss from the surgical site. Through a systematic review of published and ongoing investigations on topical TXA for spinal surgery, we wish to make spine practitioners aware of this option and to suggest opportunities for further investigation in the field. Methods A narrative review of systemic TXA in spinal surgery and topical TXA in surgery was conducted. Furthermore, a systematic search (using PRISMA guidelines) of PubMed (MEDLINE), EMBASE, and Cochrane CENTRAL databases as well as World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov (National Institutes of Health), and International Standard Randomized Controlled Trial Number registries was conducted to identify both published literature and ongoing clinical trials on topical TXA in spinal surgery. Results Of 1,631 preliminary search results, 2 published studies were included in the systematic review. Out of 285 ongoing clinical trials matching the search criteria, a total of 4 relevant studies were included and reviewed. Conclusion Intravenous TXA is established as an efficacious hemostatic agent in spinal surgery. Use of topical TXA in surgery suggests similar hemostatic efficacy and potentially improved safety as compared with intravenous TXA. For spinal surgery, the literature on topical TXA is sparse but promising, warranting further clinical investigation and consideration as a clinical option in cases with significant anticipated surgical site blood loss. PMID:27099820

[A robotic system for gait re-education in patients with an incomplete spinal cord injury].

PubMed

Esclarín-De Ruz, A; Alcobendas-Maestro, M; Casado-López, R; Muñoz-Gonzalez, A; Florido-Sánchez, M A; González-Valdizán, E

A spinal cord injury involves the loss or alteration of motor patterns in walking, the recovery of which depends partly on the rearrangement of the preserved neural circuits. AIM. To evaluate the changes that take place in the gait of patients with incomplete spinal cord injuries who were treated with a robotic walking system in association with conventional therapy. The study conducted was an open-label, prospective, descriptive trial with statistical inference in patients with C2-L3 spinal cord injuries that were classified as degrees C and D according to the American Spinal Injury Association (ASIA) scale. The variables that were analysed on the first and the last day of the study were: number of walkers, 10-m gait test, the Walking Index for Spinal Cord Injury scale revision, technical aids, muscle balance in the lower limbs, locomotor subscale of the measure of functional independence, modified Ashworth scale for spasticity and the visual analogue scale for pain. At the end, data were recorded from the impression of change scale. The analysis was conducted by means of Student's t, chi squared and Pearson's correlation; p < or = 0.05. Forty-five patients, with a mean age of 44 +/- 14.3 years, finished the study; 76% were males, injury was caused by trauma in 58% of cases, and the time of progression was 139 +/- 70 days. Statistically significant increases were observed in the number of subjects capable of walking, walking speed, less need for technical aids, strength in the lower limbs and independence in activities of daily living. Treatment using the robotic system in association with conventional therapy improves walking capacity in patients with incomplete spinal cord injuries.

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

A computer vision system for diagnosing scoliosis using moiré images.

PubMed

Batouche, M; Benlamri, R; Kholladi, M K

1996-07-01

For young people, scoliosis deformities are an evolving process which must be detected and treated as early as possible. The moiré technique is simple, inexpensive, not aggressive and especially convenient for detecting spinal deformations. Doctors make their diagnosis by analysing the symmetry of fringes obtained by such techniques. In this paper, we present a computer vision system for help diagnosing spinal deformations using noisy moiré images of the human back. The approach adopted in this paper consists of extracting fringe contours from moiré images, then localizing some anatomical features (the spinal column, lumbar hollow and shoulder blades) which are crucial for 3D surface generation carried out using Mota's relaxation operator. Finally, rules furnished by doctors are used to derive the kind of spinal deformation and to yield the diagnosis. The proposed system has been tested on a set of noisy moiré images, and the experimental result have shown its robustness and reliability for the recognition of most scoliosis deformities.

A differentially expressed set of microRNAs in cerebro-spinal fluid (CSF) can diagnose CNS malignancies

PubMed Central

Drusco, Alessandra; Bottoni, Arianna; Laganà, Alessandro; Acunzo, Mario; Fassan, Matteo; Cascione, Luciano; Antenucci, Anna; Kumchala, Prasanthi; Vicentini, Caterina; Gardiman, Marina P.; Alder, Hansjuerg; Carosi, Mariantonia A.; Ammirati, Mario; Gherardi, Stefano; Luscrì, Marilena; Carapella, Carmine; Zanesi, Nicola; Croce, Carlo M.

2015-01-01

Central Nervous System malignancies often require stereotactic biopsy or biopsy for differential diagnosis, and for tumor staging and grading. Furthermore, stereotactic biopsy can be non-diagnostic or underestimate grading. Hence, there is a compelling need of new diagnostic biomarkers to avoid such invasive procedures. Several biological markers have been proposed, but they can only identify specific prognostic subtype of Central Nervous System tumors, and none of them has found a standardized clinical application. The aim of the study was to identify a Cerebro-Spinal Fluid microRNA signature that could differentiate among Central Nervous System malignancies. CSF total RNA of 34 neoplastic and of 14 non-diseased patients was processed by NanoString. Comparison among groups (Normal, Benign, Glioblastoma, Medulloblastoma, Metastasis and Lymphoma) lead to the identification of a microRNA profile that was further confirmed by RT-PCR and in situ hybridization. Hsa-miR-451, -711, 935, -223 and -125b were significantly differentially expressed among the above mentioned groups, allowing us to draw an hypothetical diagnostic chart for Central Nervous System malignancies. This is the first study to employ the NanoString technique for Cerebro-Spinal Fluid microRNA profiling. In this article, we demonstrated that Cerebro-Spinal Fluid microRNA profiling mirrors Central Nervous System physiologic or pathologic conditions. Although more cases need to be tested, we identified a diagnostic Cerebro-Spinal Fluid microRNA signature with good perspectives for future diagnostic clinical applications. PMID:26246487

A differentially expressed set of microRNAs in cerebro-spinal fluid (CSF) can diagnose CNS malignancies.

PubMed

Drusco, Alessandra; Bottoni, Arianna; Laganà, Alessandro; Acunzo, Mario; Fassan, Matteo; Cascione, Luciano; Antenucci, Anna; Kumchala, Prasanthi; Vicentini, Caterina; Gardiman, Marina P; Alder, Hansjuerg; Carosi, Mariantonia A; Ammirati, Mario; Gherardi, Stefano; Luscrì, Marilena; Carapella, Carmine; Zanesi, Nicola; Croce, Carlo M

2015-08-28

Central Nervous System malignancies often require stereotactic biopsy or biopsy for differential diagnosis, and for tumor staging and grading. Furthermore, stereotactic biopsy can be non-diagnostic or underestimate grading. Hence, there is a compelling need of new diagnostic biomarkers to avoid such invasive procedures. Several biological markers have been proposed, but they can only identify specific prognostic subtype of Central Nervous System tumors, and none of them has found a standardized clinical application.The aim of the study was to identify a Cerebro-Spinal Fluid microRNA signature that could differentiate among Central Nervous System malignancies.CSF total RNA of 34 neoplastic and of 14 non-diseased patients was processed by NanoString. Comparison among groups (Normal, Benign, Glioblastoma, Medulloblastoma, Metastasis and Lymphoma) lead to the identification of a microRNA profile that was further confirmed by RT-PCR and in situ hybridization.Hsa-miR-451, -711, 935, -223 and -125b were significantly differentially expressed among the above mentioned groups, allowing us to draw an hypothetical diagnostic chart for Central Nervous System malignancies.This is the first study to employ the NanoString technique for Cerebro-Spinal Fluid microRNA profiling. In this article, we demonstrated that Cerebro-Spinal Fluid microRNA profiling mirrors Central Nervous System physiologic or pathologic conditions. Although more cases need to be tested, we identified a diagnostic Cerebro-Spinal Fluid microRNA signature with good perspectives for future diagnostic clinical applications.

Gaskell revisited: new insights into spinal autonomics necessitate a revised motor neuron nomenclature.

PubMed

Fritzsch, Bernd; Elliott, Karen L; Glover, Joel C

2017-11-01

Several concepts developed in the nineteenth century have formed the basis of much of our neuroanatomical teaching today. Not all of these were based on solid evidence nor have withstood the test of time. Recent evidence on the evolution and development of the autonomic nervous system, combined with molecular insights into the development and diversification of motor neurons, challenges some of the ideas held for over 100 years about the organization of autonomic motor outflow. This review provides an overview of the original ideas and quality of supporting data and contrasts this with a more accurate and in depth insight provided by studies using modern techniques. Several lines of data demonstrate that branchial motor neurons are a distinct motor neuron population within the vertebrate brainstem, from which parasympathetic visceral motor neurons of the brainstem evolved. The lack of an autonomic nervous system in jawless vertebrates implies that spinal visceral motor neurons evolved out of spinal somatic motor neurons. Consistent with the evolutionary origin of brainstem parasympathetic motor neurons out of branchial motor neurons and spinal sympathetic motor neurons out of spinal motor neurons is the recent revision of the organization of the autonomic nervous system into a cranial parasympathetic and a spinal sympathetic division (e.g., there is no sacral parasympathetic division). We propose a new nomenclature that takes all of these new insights into account and avoids the conceptual misunderstandings and incorrect interpretation of limited and technically inferior data inherent in the old nomenclature.

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

PubMed

Rupp, R; Abel, R

2005-02-01

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

A spatial registration method for navigation system combining O-arm with spinal surgery robot

NASA Astrophysics Data System (ADS)

Bai, H.; Song, G. L.; Zhao, Y. W.; Liu, X. Z.; Jiang, Y. X.

2018-05-01

The minimally invasive surgery in spinal surgery has become increasingly popular in recent years as it reduces the chances of complications during post-operation. However, the procedure of spinal surgery is complicated and the surgical vision of minimally invasive surgery is limited. In order to increase the quality of percutaneous pedicle screw placement, the O-arm that is a mobile intraoperative imaging system is used to assist surgery. The robot navigation system combined with O-arm is also increasing, with the extensive use of O-arm. One of the major problems in the surgical navigation system is to associate the patient space with the intra-operation image space. This study proposes a spatial registration method of spinal surgical robot navigation system, which uses the O-arm to scan a calibration phantom with metal calibration spheres. First, the metal artifacts were reduced in the CT slices and then the circles in the images based on the moments invariant could be identified. Further, the position of the calibration sphere in the image space was obtained. Moreover, the registration matrix is obtained based on the ICP algorithm. Finally, the position error is calculated to verify the feasibility and accuracy of the registration method.

Contribution of supraspinal systems to generation of automatic postural responses

PubMed Central

Deliagina, Tatiana G.; Beloozerova, Irina N.; Orlovsky, Grigori N.; Zelenin, Pavel V.

2014-01-01

Different species maintain a particular body orientation in space due to activity of the closed-loop postural control system. In this review we discuss the role of neurons of descending pathways in operation of this system as revealed in animal models of differing complexity: lower vertebrate (lamprey) and higher vertebrates (rabbit and cat). In the lamprey and quadruped mammals, the role of spinal and supraspinal mechanisms in the control of posture is different. In the lamprey, the system contains one closed-loop mechanism consisting of supraspino-spinal networks. Reticulospinal (RS) neurons play a key role in generation of postural corrections. Due to vestibular input, any deviation from the stabilized body orientation leads to activation of a specific population of RS neurons. Each of the neurons activates a specific motor synergy. Collectively, these neurons evoke the motor output necessary for the postural correction. In contrast to lampreys, postural corrections in quadrupeds are primarily based not on the vestibular input but on the somatosensory input from limb mechanoreceptors. The system contains two closed-loop mechanisms – spinal and spino-supraspinal networks, which supplement each other. Spinal networks receive somatosensory input from the limb signaling postural perturbations, and generate spinal postural limb reflexes. These reflexes are relatively weak, but in intact animals they are enhanced due to both tonic supraspinal drive and phasic supraspinal commands. Recent studies of these supraspinal influences are considered in this review. A hypothesis suggesting common principles of operation of the postural systems stabilizing body orientation in a particular plane in the lamprey and quadrupeds, that is interaction of antagonistic postural reflexes, is discussed. PMID:25324741

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.

Spinal Endomorphin 2 Antinociception and the Mechanisms That Produce It Are Both Sex- and Stage of Estrus Cycle–Dependent in Rats

PubMed Central

Liu, Nai-Jiang; Gintzler, Alan R.

2014-01-01

Endomorphin 2 (EM2) is the predominant endogenous mu-opioid receptor (MOR) ligand in the spinal cord. Given its endogenous presence, antinociceptive responsiveness to the intrathecal application of EM2 most likely reflects its ability to modulate nociception when released in situ. In order to explore the physiological pliability of sex-dependent differences in spinal MOR-mediated antinociception, we investigated the antinociception produced by intrathecal EM2 in male, proestrus female, and diestrus female rats. Antinociception was reflected by changes in tail flick latency to radiant heat. In females, the spinal EM2 antinociceptive system oscillated between analgesically active and inactive states. During diestrus, when circulating estrogens are low, spinal EM2 antinociceptive responsiveness was minimal. In contrast, during proestrus, when circulating estrogens are high, spinal EM2 antinociception was robust and comparable in magnitude to that manifest by males. Furthermore, in proestrus females, spinal EM2 antinociception required spinal dynorphin and kappaopioid receptor activation, concomitant with MOR activation. This is required for neither spinal EM2 antinociception in males nor the antinociception elicited in proestrus females by spinal sufentanil or [d-Ala2,N-methyl-Phe4,Gly-ol5]-enkephalin, which are prototypic MOR-selective nonpeptide and peptide agonists, respectively. These results reveal that spinal EM2 antinociception and the signaling mechanisms used to produce it fundamentally differ in males and females. Perspective The inability to mount spinal EM2 antinociception during defined stages of the estrus (and presumably menstrual) cycle and impaired transition from spinal EM2 analgesically nonresponsive to responsive physiological states could be causally associated with the well-documented greater severity and frequency of chronic intractable pain syndromes in women vs men. PMID:24084000

Agreement between fiber optic and optoelectronic systems for quantifying sagittal plane spinal curvature in sitting.

PubMed

Cloud, Beth A; Zhao, Kristin D; Breighner, Ryan; Giambini, Hugo; An, Kai-Nan

2014-07-01

Spinal posture affects how individuals function from a manual wheelchair. There is a need to directly quantify spinal posture in this population to ultimately improve function. A fiber optic system, comprised of an attached series of sensors, is promising for measuring large regions of the spine in individuals sitting in a wheelchair. The purpose of this study was to determine the agreement between fiber optic and optoelectronic systems for measuring spinal curvature, and describe the range of sagittal plane spinal curvatures in natural sitting. Able-bodied adults (n = 26, 13 male) participated. Each participant assumed three sitting postures: natural, slouched (accentuated kyphosis), and extension (accentuated lordosis) sitting. Fiber optic (ShapeTape) and optoelectronic (Optotrak) systems were applied to the skin over spinous processes from S1 to C7 and used to measure sagittal plane spinal curvature. Regions of kyphosis and lordosis were identified. A Cobb angle-like method was used to quantify lordosis and kyphosis. Generalized linear model and Bland-Altman analyses were used to assess agreement. A strong correlation exists between curvature values obtained with Optotrak and ShapeTape (R(2) = 0.98). The mean difference between Optotrak and ShapeTape for kyphosis in natural, extension, and slouched postures was 4.30° (95% LOA: -3.43 to 12.04°), 3.64° (95% LOA: -1.07 to 8.36°), and 4.02° (95% LOA: -2.80 to 10.84°), respectively. The mean difference for lordosis, when present, in natural and extension postures was 2.86° (95% LOA: -1.18 to 6.90°) and 2.55° (95% LOA: -3.38 to 8.48°), respectively. In natural sitting, the mean ± SD of kyphosis values was 35.07 ± 6.75°. Lordosis was detected in 8/26 participants: 11.72 ± 7.32°. The fiber optic and optoelectronic systems demonstrate acceptable agreement for measuring sagittal plane thoracolumbar spinal curvature. Copyright © 2014 Elsevier B.V. All rights reserved.

Syndrome of the anterior spinal artery as the primary manifestation of aspergillosis.

PubMed

Pfausler, B; Kampfl, A; Berek, K; Maier, H; Aichner, F; Schmutzhard, E

1995-01-01

Aspergillosis of the central nervous system (CNS) is an uncommon infection, mainly occurring in immunocompromised patients. Beside cerebral involvement spinal cord lesions are extremely rare. To our knowledge, aspergillosis initially presenting with acute paraplegia due to mycotic thrombosis of the anterior spinal artery in a formerly healthy patient has, so far, not been reported. Neither a primary focus nor an underlying disease had been detected.

Automated quantitative gait analysis during overground locomotion in the rat: its application to spinal cord contusion and transection injuries.

PubMed

Hamers, F P; Lankhorst, A J; van Laar, T J; Veldhuis, W B; Gispen, W H

2001-02-01

Analysis of locomotion is an important tool in the study of peripheral and central nervous system damage. Most locomotor scoring systems in rodents are based either upon open field locomotion assessment, for example, the BBB score or upon foot print analysis. The former yields a semiquantitative description of locomotion as a whole, whereas the latter generates quantitative data on several selected gait parameters. In this paper, we describe the use of a newly developed gait analysis method that allows easy quantitation of a large number of locomotion parameters during walkway crossing. We were able to extract data on interlimb coordination, swing duration, paw print areas (total over stance, and at 20-msec time resolution), stride length, and base of support: Similar data can not be gathered by any single previously described method. We compare changes in gait parameters induced by two different models of spinal cord injury in rats, transection of the dorsal half of the spinal cord and spinal cord contusion injury induced by the NYU or MASCIS device. Although we applied this method to rats with spinal cord injury, the usefulness of this method is not limited to rats or to the investigation of spinal cord injuries alone.

Liposomal cytarabine in prophylaxis or curative treatment of central nervous system involvement in Burkitt leukemia/lymphoma.

PubMed

Segot, Amandine; Raffoux, Emmanuel; Lengline, Etienne; Thieblemont, Catherine; Dombret, Hervé; Boissel, Nicolas; Cluzeau, Thomas

2015-11-01

In recent years, the outcome of Burkitt leukemia/lymphoma (BL) has improved significantly. Central nervous system (CNS) involvement continues to be a poor prognostic indicator. High doses of intravenous polychemotherapy, intrathecal chemotherapy, and cranio-spinal radiation therapy are used by numerous groups. Majority of patients are cured after this strategy. The next challenge is to decrease toxicities of treatment, including long-term toxicities secondary to cranio-spinal radiation therapy observed in these cured patients. Liposomal cytarabine could be a good alternative to cranio-spinal radiation therapy as already reported in acute lymphoblastic leukemia. We report here eleven patients treated in our center for BL, with liposomal cytarabine instead of cranio-spinal radiation therapy as prophylactic or curative treatment for CNS involvement. Treatment was safe with no short-term grade >3 adverse events. Moreover, no long-term side effects and no impact on outcome were observed. We conclude that LC could be a good option to decrease short/long-term side effects of cranio-spinal radiation therapy in BL and could be evaluated in a future clinical trial.

A Low-Cost, Passive Navigation Training System for Image-Guided Spinal Intervention.

PubMed

Lorias-Espinoza, Daniel; Carranza, Vicente González; de León, Fernando Chico-Ponce; Escamirosa, Fernando Pérez; Martinez, Arturo Minor

2016-11-01

Navigation technology is used for training in various medical specialties, not least image-guided spinal interventions. Navigation practice is an important educational component that allows residents to understand how surgical instruments interact with complex anatomy and to learn basic surgical skills such as the tridimensional mental interpretation of bidimensional data. Inexpensive surgical simulators for spinal surgery, however, are lacking. We therefore designed a low-cost spinal surgery simulator (Spine MovDigSys 01) to allow 3-dimensional navigation via 2-dimensional images without altering or limiting the surgeon's natural movement. A training system was developed with an anatomical lumbar model and 2 webcams to passively digitize surgical instruments under MATLAB software control. A proof-of-concept recognition task (vertebral body cannulation) and a pilot test of the system with 12 neuro- and orthopedic surgeons were performed to obtain feedback on the system. Position, orientation, and kinematic variables were determined and the lateral, posteroanterior, and anteroposterior views obtained. The system was tested with a proof-of-concept experimental task. Operator metrics including time of execution (t), intracorporeal length (d), insertion angle (α), average speed (v¯), and acceleration (a) were obtained accurately. These metrics were converted into assessment metrics such as smoothness of operation and linearity of insertion. Results from initial testing are shown and the system advantages and disadvantages described. This low-cost spinal surgery training system digitized the position and orientation of the instruments and allowed image-guided navigation, the generation of metrics, and graphic recording of the instrumental route. Spine MovDigSys 01 is useful for development of basic, noninnate skills and allows the novice apprentice to quickly and economically move beyond the basics. Copyright © 2016 Elsevier Inc. All rights reserved.

Lumbar spine disc heights and curvature: upright posture vs. supine compression harness

NASA Technical Reports Server (NTRS)

Lee, Shi-Uk; Hargens, Alan R.; Fredericson, Michael; Lang, Philipp K.

2003-01-01

INTRODUCTION: Spinal lengthening in microgravity is thought to cause back pain in astronauts. A spinal compression harness can compress the spine to eliminate lengthening but the loading condition with harness is different than physiologic conditions. Our purpose was to compare the effect of spine compression with a harness in supine position on disk height and spinal curvature in the lumbar spine to that of upright position as measured using a vertically open magnetic resonance imaging system. METHODS: Fifteen healthy subjects volunteered. On day 1, each subject lay supine for an hour and a baseline scan of the lumbar spine was performed. After applying a load of fifty percent of body weight with the harness for thirty minutes, the lumbar spine was scanned again. On day 2, after a baseline scan, a follow up scan was performed after kneeling for thirty minutes within the gap between two vertically oriented magnetic coils. Anterior and posterior disk heights, posterior disk bulging, and spinal curvature were measured from the baseline and follow up scans. RESULTS: Anterior disk heights increased and posterior disk heights decreased compared with baseline scans both after spinal compression with harness and upright posture. The spinal curvature increased by both loading conditions of the spine. DISCUSSION: The spinal compression with specially designed harness has the same effect as the physiologic loading of the spine in the kneeling upright position. The harness shows some promise as a tool to increase the diagnostic capabilities of a conventional MR system.

10 kHz High-Frequency Spinal Cord Stimulation for Chronic Axial Low Back Pain in Patients With No History of Spinal Surgery: A Preliminary, Prospective, Open Label and Proof-of-Concept Study.

PubMed

Al-Kaisy, Adnan; Palmisani, Stefano; Smith, Thomas E; Pang, David; Lam, Khai; Burgoyne, William; Houghton, Russell; Hudson, Emma; Lucas, Jonathan

2017-01-01

To explore the effectiveness of 10 kHz high frequency spinal cord stimulation (HF10 therapy) treatment of chronic low back pain in patients who have not had spinal surgery. Patients with chronic low back pain without prior spinal surgery were evaluated by a team of spine surgeons to rule out any spinal pathology amenable to surgical interventions and by a multidisciplinary pain team to confirm eligibility for the study. After a successful (>50% back pain reduction) trial of HF10 therapy, enrolled subjects underwent permanent system implantation and were followed-up one year post-implant. About 95% of the enrolled subjects (20/21) received the permanent system. At 12 months post-implant, both back pain VAS score and ODI were significantly reduced compared with baseline values (by 73% and 48%, respectively); an estimated quality-adjusted life year gain of 0.47 and a reduction in opioid use by 64% was observed. Four more patients among those unable to work at baseline due to back pain were employed at 12 months post-implant. There were no serious adverse events. HF10 therapy may provide significant back pain relief, reduction in disability, improvement quality of life, and reduction in opioid use in chronic low back pain not resulting from spinal surgery. © 2016 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.

Anatomy of the Spinal Meninges.

PubMed

Sakka, Laurent; Gabrillargues, Jean; Coll, Guillaume

2016-06-01

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

21 CFR 888.3070 - Pedicle screw spinal system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... treatment of the following acute and chronic instabilities or deformities of the thoracic, lumbar, and... spondylolisthesis with objective evidence of neurologic impairment; fracture; dislocation; scoliosis; kyphosis... with objective evidence of neurologic impairment, fracture, dislocation, scoliosis, kyphosis, spinal...

21 CFR 888.3070 - Pedicle screw spinal system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... treatment of the following acute and chronic instabilities or deformities of the thoracic, lumbar, and... spondylolisthesis with objective evidence of neurologic impairment; fracture; dislocation; scoliosis; kyphosis... with objective evidence of neurologic impairment, fracture, dislocation, scoliosis, kyphosis, spinal...

A novel spinal kinematic analysis using X-ray imaging and vicon motion analysis: a case study.

PubMed

Noh, Dong K; Lee, Nam G; You, Joshua H

2014-01-01

This study highlights a novel spinal kinematic analysis method and the feasibility of X-ray imaging measurements to accurately assess thoracic spine motion. The advanced X-ray Nash-Moe method and analysis were used to compute the segmental range of motion in thoracic vertebra pedicles in vivo. This Nash-Moe X-ray imaging method was compared with a standardized method using the Vicon 3-dimensional motion capture system. Linear regression analysis showed an excellent and significant correlation between the two methods (R2 = 0.99, p < 0.05), suggesting that the analysis of spinal segmental range of motion using X-ray imaging measurements was accurate and comparable to the conventional 3-dimensional motion analysis system. Clinically, this novel finding is compelling evidence demonstrating that measurements with X-ray imaging are useful to accurately decipher pathological spinal alignment and movement impairments in idiopathic scoliosis (IS).

The Postnatal Development of Spinal Sensory Processing

NASA Astrophysics Data System (ADS)

Fitzgerald, Maria; Jennings, Ernest

1999-07-01

The mechanisms by which infants and children process pain should be viewed within the context of a developing sensory nervous system. The study of the neurophysiological properties and connectivity of sensory neurons in the developing spinal cord dorsal horn of the intact postnatal rat has shed light on the way in which the newborn central nervous system analyzes cutaneous innocuous and noxious stimuli. The receptive field properties and evoked activity of newborn dorsal horn cells to single repetitive and persistent innocuous and noxious inputs are developmentally regulated and reflect the maturation of excitatory transmission within the spinal cord. These changes will have an important influence on pain processing in the postnatal period.

Transverse tripolar spinal cord stimulation: theoretical performance of a dual channel system.

PubMed

Struijk, J J; Holsheimer, J

1996-07-01

A new approach to spinal cord stimulation is presented, by which several serious problems of conventional methods can be solved. A transverse tripolar electrode with a dual-channel voltage stimulator is evaluated theoretically by means of a volume conductor model, combined with nerve fibre models. The simulations predict that a high degree of freedom in the control of activation of dorsal spinal pathways may be obtained with the described system. This implies an easier control of paraesthesia coverage of skin areas and the possibility to correct undesired paraesthesia patterns, caused by lead migration, tissue growth, or anatomical asymmetries, for example, without surgical intervention. It will also be possible to preferentially activate either dorsal column or dorsal root fibres, which has some important clinical advantages. Compared to conventional stimulation systems, the new system has a relatively high current drain.

Symptomatic Spinal Epidural Lipomatosis After a Single Local Epidural Steroid Injection

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

Tok, Chung Hong, E-mail: rogertok@gmail.com; Kaur, Shaleen; Gangi, Afshin

Spinal epidural lipomatosis is a rare disorder that can manifest with progressive neurological deficits. It is characterized by abnormal accumulation of unencapsulated epidural fat commonly associated with the administration of exogenous steroids associated with a variety of systemic diseases, endocrinopathies, and Cushing syndrome (Fogel et al. Spine J 5:202-211, 2005). Occasionally, spinal epidural lipomatosis may occur in patients not exposed to steroids or in patients with endocrinopathies, primarily in obese individuals (Fogel et al. Spine J 5:202-211, 2005). However, spinal lumbar epidural lipomatosis resulting from local steroid injection has rarely been reported. We report the case of a 45-year-old diabeticmore » man with claudication that was probably due to symptomatic lumbar spinal lipomatosis resulting from a single local epidural steroid injection.« less

A Case of Hemiabdominal Myoclonus.

PubMed

Nociti, Viviana; Servidei, Serenella; Luigetti, Marco; Iorio, Raffaele; Lo Monaco, Mauro; Mirabella, Massimiliano; Frisullo, Giovanni; Della Marca, Giacomo

2015-10-01

Myoclonus consists of sudden, brief, involuntary jerky muscular contractions. Central and peripheral nervous system lesions are involved in the pathogenesis of this movement disorder. Symptomatic or secondary spinal myoclonus is the most common form. A 68-year-old woman was diagnosed with hemiabdominal spinal myoclonus. Occasional and very mild involuntary repetitive movements of the hemiabdomen began immediately after surgery for uterine cancer. After surgery for laparocele, secondary to the uterine cancer surgery, performed under spinal anesthesia, there was severe worsening of movements. Neuroradiological investigations failed to demonstrate spinal injury, while neurophysiological studies showed impairment of the right central somatosensory pathway. Considering the low resolution of magnetic resonance imaging in the evaluation of thoracic level, we suggest an extensive neurophysiological evaluation in patients with spinal myoclonus. © EEG and Clinical Neuroscience Society (ECNS) 2014.

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

PubMed Central

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

2016-01-01

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

Dimethylarginine dimethylaminohydrolase 1 is involved in spinal nociceptive plasticity.

PubMed

DʼMello, Richard; Sand, Claire A; Pezet, Sophie; Leiper, James M; Gaurilcikaite, Egle; McMahon, Stephen B; Dickenson, Anthony H; Nandi, Manasi

2015-10-01

Activation of neuronal nitric oxide synthase, and consequent production of nitric oxide (NO), contributes to spinal hyperexcitability and enhanced pain sensation. All NOS isoforms are inhibited endogenously by asymmetric dimethylarginine, which itself is metabolised by dimethylarginine dimethylaminohydrolase (DDAH). Inhibition of DDAH can indirectly attenuate NO production by elevating asymmetric dimethylarginine concentrations. Here, we show that the DDAH-1 isoform is constitutively active in the nervous system, specifically in the spinal dorsal horn. DDAH-1 was found to be expressed in sensory neurons within both the dorsal root ganglia and spinal dorsal horn; L-291 (NG-[2-Methoxyethyl]-L-arginine methyl ester), a DDAH-1 inhibitor, reduced NO synthesis in cultured dorsal root ganglia neurons. Spinal application of L-291 decreased N-methyl-D-aspartate-dependent postdischarge and windup of dorsal horn sensory neurons--2 measures of spinal hyperexcitability. Finally, spinal application of L-291 reduced both neuronal and behavioral measures of formalin-induced central sensitization. Thus, DDAH-1 may be a potential therapeutic target in neuronal disorders, such as chronic pain, where elevated NO is a contributing factor.

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.

Predictive value of Tokuhashi scoring systems in spinal metastases, focusing on various primary tumor groups: evaluation of 448 patients in the Aarhus spinal metastases database.

PubMed

Wang, Miao; Bünger, Cody Eric; Li, Haisheng; Wu, Chunsen; Høy, Kristian; Niedermann, Bent; Helmig, Peter; Wang, Yu; Jensen, Anders Bonde; Schättiger, Katrin; Hansen, Ebbe Stender

2012-04-01

We conducted a prospective cohort study of 448 patients with spinal metastases from a variety of cancer groups. To determine the specific predictive value of the Tokuhashi scoring system (T12) and its revised version (T15) in spinal metastases of various primary tumors. The life expectancy of patients with spinal metastases is one of the most important factors in selecting the treatment modality. Tokuhashi et al formulated a prognostic scoring system with a total sum of 12 points for preoperative prediction of life expectancy in 1990 and revised it in 2005 to a total sum of 15 points. There is a lack of knowledge about the specific predictive value of those scoring systems in patients with spinal metastases from a variety of cancer groups. We included 448 patients with vertebral metastases who underwent surgical treatment during November 1992 to November 2009 in Aarhus University Hospital NBG. Data were retrieved from Aarhus Metastases Database. Scores based on T12 and T15 were calculated prospectively for each patient. We divided all the patients into different groups dictated by the site of their primary tumor. Predictive value and accuracy rate of the 2 scoring systems were compared in each cancer group. Both the T12 and T15 scoring systems showed statistically significant predictive value when the 448 patients were analyzed in total (T12, P < 0.0001; T15, P < 0.0001). The accuracy rate was significantly higher in T15 (P < 0.0001) than in T12. The further analyses by primary cancer groups showed that the predictive value of T12 and T15 was primarily determined by the prostate (P = 0.0003) and breast group (P = 0.0385). Only T12 displayed predictive value in the colon group (P = 0.0011). Neither of the scoring systems showed significant predictive value in the lung (P > 0.05), renal (P > 0.05), or miscellaneous primary tumor groups (P > 0.05). The accuracy rate of prognosis in T15 was significantly improved in the prostate (P = 0.0032) and breast group (P < 0.0001). Both T12 and T15 showed significant predictive value in patients with spinal metastases. T15 has a statistically higher accuracy rate than T12. Among the various cancer groups, the 2 scoring systems are especially reliable in prostate and breast metastases groups. T15 is recommended as superior to T12 because of its higher accuracy rate.

Earthquake-related versus non-earthquake-related injuries in spinal injury patients: differentiation with multidetector computed tomography

PubMed Central

2010-01-01

Introduction In recent years, several massive earthquakes have occurred across the globe. Multidetector computed tomography (MDCT) is reliable in detecting spinal injuries. The purpose of this study was to compare the features of spinal injuries resulting from the Sichuan earthquake with those of non-earthquake-related spinal trauma using MDCT. Methods Features of spinal injuries of 223 Sichuan earthquake-exposed patients and 223 non-earthquake-related spinal injury patients were retrospectively compared using MDCT. The date of non-earthquake-related spinal injury patients was collected from 1 May 2009 to 22 July 2009 to avoid the confounding effects of seasonal activity and clothing. We focused on anatomic sites, injury types and neurologic deficits related to spinal injuries. Major injuries were classified according to the grid 3-3-3 scheme of the Magerl (AO) classification system. Results A total of 185 patients (82.96%) in the earthquake-exposed cohort experienced crush injuries. In the earthquake and control groups, 65 and 92 patients, respectively, had neurologic deficits. The anatomic distribution of these two cohorts was significantly different (P < 0.001). Cervical spinal injuries were more common in the control group (risk ratio (RR) = 2.12, P < 0.001), whereas lumbar spinal injuries were more common in the earthquake-related spinal injuries group (277 of 501 injured vertebrae; 55.29%). The major types of injuries were significantly different between these cohorts (P = 0.002). Magerl AO type A lesions composed most of the lesions seen in both of these cohorts. Type B lesions were more frequently seen in earthquake-related spinal injuries (RR = 1.27), while we observed type C lesions more frequently in subjects with non-earthquake-related spinal injuries (RR = 1.98, P = 0.0029). Conclusions Spinal injuries sustained in the Sichuan earthquake were located mainly in the lumbar spine, with a peak prevalence of type A lesions and a high occurrence of neurologic deficits. The anatomic distribution and type of spinal injuries that varied between earthquake-related and non-earthquake-related spinal injury groups were perhaps due to the different mechanism of injury. PMID:21190568

Pharmacodynamic and pharmacokinetic studies of agmatine after spinal administration in the mouse.

PubMed

Roberts, John C; Grocholski, Brent M; Kitto, Kelley F; Fairbanks, Carolyn A

2005-09-01

Agmatine is an endogenous decarboxylation product of arginine that has been previously shown to antagonize the N-methyl-d-aspartate (NMDA) receptor and inhibit nitric-oxide synthase. Many neuropharmacological studies have shown that exogenous administration of agmatine prevents or reverses biological phenomena dependent on central nervous system glutamatergic systems, including opioid-induced tolerance, opioid self-administration, and chronic pain. However, the central nervous system (CNS) pharmacokinetic profile of agmatine remains minimally defined. The present study determined the spinal cord pharmacokinetics and acute pharmacodynamics of intrathecally administered agmatine in mice. After a single bolus intrathecal injection, agmatine concentrations in spinal cord (cervical, thoracic, and lumbosacral) tissue and serum were quantified by an isocratic high-performance liquid chromatography fluorescence detection system. Agmatine persisted at near maximum concentrations in all levels of the spinal cord for several hours with a half-life of approximately 12 h. Initial agmatine concentrations in serum were 10% those in CNS. However, the serum half-life was less than 10 min after intrathecal injection of agmatine, consistent with previous preliminary pharmacokinetic reports of systemically administered agmatine. The pharmacodynamic response to agmatine in the NMDA-nociceptive behavior and thermal hyperalgesia tests was assessed. Whereas MK-801 (dizocilpine maleate) inhibits these two responses with equal potency, agmatine inhibits the thermal hyperalgesia with significantly increased potency compared with the nociceptive behavior, suggesting two sites of action. In contrast to the pharmacokinetic results, the agmatine inhibition of both behaviors had a duration of only 10 to 30 min. Collectively, these results suggest the existence of a currently undefined agmatinergic extracellular clearance process in spinal cord.

Augmentation of systemic blood pressure during spinal cord ischemia to prevent postoperative paraplegia after aortic surgery in a rabbit model.

PubMed

Izumi, So; Okada, Kenji; Hasegawa, Tomomi; Omura, Atsushi; Munakata, Hiroshi; Matsumori, Masamichi; Okita, Yutaka

2010-05-01

Paraplegia from spinal cord ischemia remains an unresolved complication in thoracoabdominal aortic surgery, with high morbidity and mortality. This study investigated postoperative effects of systemic blood pressure augmentation during ischemia. Spinal cord ischemia was induced in rabbits by infrarenal aortic occlusion for 15 minutes with infused phenylephrine (high blood pressure group, n = 8) or nitroprusside (low blood pressure group, n = 8) or without vasoactive agent (control, n = 8). Spinal cord blood flow, transcranial motor evoked potentials, neurologic outcome, and motor neuron cell damage (apoptosis, necrosis, superoxide generation, myeloperoxidase activity) were evaluated. Mean arterial pressures during ischemia were controlled at 121.9 +/- 2.8, 50.8 +/- 4.3, and 82.3 +/- 10.7 mm Hg in high blood pressure, low blood pressure, and control groups, respectively. In high blood pressure group, high spinal cord blood flow (P < .01), fast recovery of transcranial motor evoked potentials (P < .01), and high neurologic score (P < .05) were observed after ischemia relative to low blood pressure and control groups. At 48 hours after ischemia, there were significantly more viable neurons, fewer terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive neurons, and less alpha-fodrin expression in high blood pressure group than low blood pressure and control groups. Superoxide generation and myeloperoxidase activity at 3 hours after ischemia were suppressed in high blood pressure group relative to low blood pressure group. Augmentation of systemic blood pressure during spinal cord ischemia can reduce ischemic insult and postoperative neurologic adverse events. 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Real-time ultrasound-guided spinal anesthesia using the SonixGPS® needle tracking system: a case report.

PubMed

Wong, Simon W; Niazi, Ahtsham U; Chin, Ki J; Chan, Vincent W

2013-01-01

The SonixGPS® is an electromagnetic needle tracking system for ultrasound-guided needle intervention. Both current and predicted needle tip position are displayed on the ultrasound screen in real-time, facilitating needle-beam alignment and guidance to the target. This case report illustrates the use of the SonixGPS system for successful performance of real-time ultrasound-guided spinal anesthesia in a patient with difficult spinal anatomy. A 67-yr-old male was admitted to our hospital to undergo revision of total right hip arthroplasty. His four previous arthroplasties for hip revision were performed under general anesthesia because he had undergone L3-L5 instrumentation for spinal stenosis. The L4-L5 interspace was viewed with the patient in the left lateral decubitus position. A 19G 80-mm proprietary needle (Ultrasonix Medical Corp, Richmond, BC, Canada) was inserted and directed through the paraspinal muscles to the ligamentum flavum in plane to the ultrasound beam. A 120-mm 25G Whitacre spinal needle was then inserted through the introducer needle in a conventional fashion. Successful dural puncture was achieved on the second attempt, as indicated by a flow of clear cerebrospinal fluid. The patient tolerated the procedure well, and the spinal anesthetic was adequate for the duration of the surgery. The SonixGPS is a novel technology that can reduce the technical difficulty of real-time ultrasound-guided neuraxial blockade. It may also have applications in other advanced ultrasound-guided regional anesthesia techniques where needle-beam alignment is critical.

Laparoscopic Cholecystectomy under Segmental Thoracic Spinal Anesthesia: A Feasible Economical Alternative.

PubMed

Kejriwal, Aditya Kumar; Begum, Shaheen; Krishan, Gopal; Agrawal, Richa

2017-01-01

Laparoscopic surgery is normally performed under general anesthesia, but regional techniques like thoracic epidural and lumbar spinal have been emerging and found beneficial. We performed a clinical case study of segmental thoracic spinal anaesthesia in a healthy patient. We selected an ASA grade I patient undergoing elective laparoscopic cholecystectomy and gave spinal anesthetic in T10-11 interspace using 1 ml of bupivacaine 5 mg ml -1 mixed with 0.5 ml of fentanyl 50 μg ml -1 . Other drugs were only given (systemically) to manage patient anxiety, pain, nausea, hypotension, or pruritus during or after surgery. The patient was reviewed 2 days postoperatively in ward. The thoracic spinal anesthetia was performed easily in the patient. Some discomfort which was readily treated with 1mg midazolam and 20 mg ketamine intravenously. There was no neurological deficit and hemodynamic parameters were in normal range intra and post-operatively and recovery was uneventful. We used a narrow gauze (26G) spinal needle which minimized the trauma to the patient and the chances of PDPH, which was more if 16 or 18G epidural needle had been used and could have increased further if there have been accidental dura puncture. Also using spinal anesthesia was economical although it should be done cautiously as we are giving spinal anesthesia above the level of termination of spinal cord.

Laparoscopic Cholecystectomy under Segmental Thoracic Spinal Anesthesia: A Feasible Economical Alternative

PubMed Central

Kejriwal, Aditya Kumar; Begum, Shaheen; Krishan, Gopal; Agrawal, Richa

2017-01-01

Laparoscopic surgery is normally performed under general anesthesia, but regional techniques like thoracic epidural and lumbar spinal have been emerging and found beneficial. We performed a clinical case study of segmental thoracic spinal anaesthesia in a healthy patient. We selected an ASA grade I patient undergoing elective laparoscopic cholecystectomy and gave spinal anesthetic in T10-11 interspace using 1 ml of bupivacaine 5 mg ml−1 mixed with 0.5 ml of fentanyl 50 μg ml−1. Other drugs were only given (systemically) to manage patient anxiety, pain, nausea, hypotension, or pruritus during or after surgery. The patient was reviewed 2 days postoperatively in ward. The thoracic spinal anesthetia was performed easily in the patient. Some discomfort which was readily treated with 1mg midazolam and 20 mg ketamine intravenously. There was no neurological deficit and hemodynamic parameters were in normal range intra and post-operatively and recovery was uneventful. We used a narrow gauze (26G) spinal needle which minimized the trauma to the patient and the chances of PDPH, which was more if 16 or 18G epidural needle had been used and could have increased further if there have been accidental dura puncture. Also using spinal anesthesia was economical although it should be done cautiously as we are giving spinal anesthesia above the level of termination of spinal cord. PMID:28928589

Spinal deformities in a wild line of Poecilia wingei bred in captivity: report of cases and review of the literature.

PubMed

Arbuatti, Alessio; Della Salda, Leonardo; Romanucci, Mariarita

2013-03-01

To describe the occurrence of various spinal deformations in a captive-bred wild line of Poecilia wingei (P. wingei). Fish belonging to a wild line of P. wingei caught from Laguna de Los Patos, Venezuela, were bred in an aquarium home-breeding system during a period of three years (2006-2009). The spinal curvature was observed to study spinal deformities in P. wingei. Out of a total of 600 fish, 22 showed different types of deformities (scoliosis, lordosis, kyphosis), with a higher incidence in females. Growth, swimming and breeding of deformed fish were generally normal. Possible causes for spinal curvature in fish are discussed on the basis of the current literature. While it is not possible to determine the exact cause(s) of spinal deformities observed in the present study, traumatic injuries, nutritional imbalances, genetic defects or a combination of these factors can be supposed to be involved in the pathogenesis of such lesions.

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.

Systemic effects induced by intralesional injection of ω-conotoxin MVIIC after spinal cord injury in rats

PubMed Central

2014-01-01

Background Calcium channel blockers such as conotoxins have shown a great potential to reduce brain and spinal cord injury. MVIIC neuroprotective effects analyzed in in vitro models of brain and spinal cord ischemia suggest a potential role of this toxin in preventing injury after spinal cord trauma. However, previous clinical studies with MVIIC demonstrated that clinical side effects might limit the usefulness of this drug and there is no research on its systemic effects. Therefore, the present study aimed to investigate the potential toxic effects of MVIIC on organs and to evaluate clinical and blood profiles of rats submitted to spinal cord injury and treated with this marine toxin. Rats were treated with placebo or MVIIC (at doses of 15, 30, 60 or 120 pmol) intralesionally following spinal cord injury. Seven days after the toxin administration, kidney, brain, lung, heart, liver, adrenal, muscles, pancreas, spleen, stomach, and intestine were histopathologically investigated. In addition, blood samples collected from the rats were tested for any hematologic or biochemical changes. Results The clinical, hematologic and biochemical evaluation revealed no significant abnormalities in all groups, even in high doses. There was no significant alteration in organs, except for degenerative changes in kidneys at a dose of 120 pmol. Conclusions These findings suggest that MVIIC at 15, 30 and 60 pmol are safe for intralesional administration after spinal cord injury and could be further investigated in relation to its neuroprotective effects. However, 120 pmol doses of MVIIC may provoke adverse effects on kidney tissue. PMID:24739121

α-Synuclein pathology in the cranial and spinal nerves in Lewy body disease.

PubMed

Nakamura, Keiko; Mori, Fumiaki; Tanji, Kunikazu; Miki, Yasuo; Toyoshima, Yasuko; Kakita, Akiyoshi; Takahashi, Hitoshi; Yamada, Masahito; Wakabayashi, Koichi

2016-06-01

Accumulation of phosphorylated α-synuclein in neurons and glial cells is a histological hallmark of Lewy body disease (LBD) and multiple system atrophy (MSA). Recently, filamentous aggregations of phosphorylated α-synuclein have been reported in the cytoplasm of Schwann cells, but not in axons, in the peripheral nervous system in MSA, mainly in the cranial and spinal nerve roots. Here we conducted an immunohistochemical investigation of the cranial and spinal nerves and dorsal root ganglia of patients with LBD. Lewy axons were found in the oculomotor, trigeminal and glossopharyngeal-vagus nerves, but not in the hypoglossal nerve. The glossopharyngeal-vagus nerves were most frequently affected, with involvement in all of 20 subjects. In the spinal nerve roots, Lewy axons were found in all of the cases examined. Lewy axons in the anterior nerves were more frequent and numerous in the thoracic and sacral segments than in the cervical and lumbar segments. On the other hand, axonal lesions in the posterior spinal nerve roots appeared to increase along a cervical-to-sacral gradient. Although Schwann cell cytoplasmic inclusions were found in the spinal nerves, they were only minimal. In the dorsal root ganglia, axonal lesions were seldom evident. These findings indicate that α-synuclein pathology in the peripheral nerves is axonal-predominant in LBD, whereas it is restricted to glial cells in MSA. © 2015 Japanese Society of Neuropathology.

Inflammatory myofibroblastic tumour of the spinal cord: case report and review of the literature.

PubMed

Despeyroux-Ewers, M; Catalaâ, I; Collin, L; Cognard, C; Loubes-Lacroix, F; Manelfe, C

2003-11-01

Inflammatory myofibroblastic tumours (IMT), also called inflammatory pseudotumours, nodular lymphoid hyperplasia, plasma-cell granuloma and fibrous xanthoma, are rare soft-tissue lesions characterised by inflammatory cells and a fibrous stroma. Clinically and radiologically, they may look like malignant tumours. They rarely affect the central nervous system and are very rare in the spinal cord. We report an IMT of the spinal cord in a 22-year-old woman presenting with spinal cord compression and a cauda equina syndrome. MRI showed a lesion at T9 with extramedullary and intramedullary components giving low signal on T2-weighted images and enhancing homogeneously. Pial lesions on the lumbar enlargement and thoracic spinal were present 11 months after surgery, when the lesion recurred. We present the radiological, operative and pathological findings and review the literature.

Effects of whole spine alignment patterns on neck responses in rear end impact.

PubMed

Sato, Fusako; Odani, Mamiko; Miyazaki, Yusuke; Yamazaki, Kunio; Östh, Jonas; Svensson, Mats

2017-02-17

The aim of this study was to investigate the whole spine alignment in automotive seated postures for both genders and the effects of the spinal alignment patterns on cervical vertebral motion in rear impact using a human finite element (FE) model. Image data for 8 female and 7 male subjects in a seated posture acquired by an upright open magnetic resonance imaging (MRI) system were utilized. Spinal alignment was determined from the centers of the vertebrae and average spinal alignment patterns for both genders were estimated by multidimensional scaling (MDS). An occupant FE model of female average size (162 cm, 62 kg; the AF 50 size model) was developed by scaling THUMS AF 05. The average spinal alignment pattern for females was implemented in the model, and model validation was made with respect to female volunteer sled test data from rear end impacts. Thereafter, the average spinal alignment pattern for males and representative spinal alignments for all subjects were implemented in the validated female model, and additional FE simulations of the sled test were conducted to investigate effects of spinal alignment patterns on cervical vertebral motion. The estimated average spinal alignment pattern was slight kyphotic, or almost straight cervical and less-kyphotic thoracic spine for the females and lordotic cervical and more pronounced kyphotic thoracic spine for the males. The AF 50 size model with the female average spinal alignment exhibited spine straightening from upper thoracic vertebra level and showed larger intervertebral angular displacements in the cervical spine than the one with the male average spinal alignment. The cervical spine alignment is continuous with the thoracic spine, and a trend of the relationship between cervical spine and thoracic spinal alignment was shown in this study. Simulation results suggested that variations in thoracic spinal alignment had a potential impact on cervical spine motion as well as cervical spinal alignment in rear end impact condition.

Local delivery of thyroid hormone enhances oligodendrogenesis and myelination after spinal cord injury

NASA Astrophysics Data System (ADS)

Shultz, Robert B.; Wang, Zhicheng; Nong, Jia; Zhang, Zhiling; Zhong, Yinghui

2017-06-01

Objective. Traumatic spinal cord injury (SCI) causes apoptosis of myelin-forming oligodendrocytes (OLs) and demyelination of surviving axons, resulting in conduction failure. Remyelination of surviving denuded axons provides a promising therapeutic target for spinal cord repair. While cell transplantation has demonstrated efficacy in promoting remyelination and functional recovery, the lack of ideal cell sources presents a major obstacle to clinical application. The adult spinal cord contains oligodendrocyte precursor cells and multipotent neural stem/progenitor cells that have the capacity to differentiate into mature, myelinating OLs. However, endogenous oligodendrogenesis and remyelination processes are limited by the upregulation of remyelination-inhibitory molecules in the post-injury microenvironment. Multiple growth factors/molecules have been shown to promote OL differentiation and myelination. Approach. In this study we screened these therapeutics and found that 3, 3‧, 5-triiodothyronine (T3) is the most effective in promoting oligodendrogenesis and OL maturation in vitro. However, systemic administration of T3 to achieve therapeutic doses in the injured spinal cord is likely to induce hyperthyroidism, resulting in serious side effects. Main results. In this study we developed a novel hydrogel-based drug delivery system for local delivery of T3 to the injury site without eliciting systemic toxicity. Significance. Using a clinically relevant cervical contusion injury model, we demonstrate that local delivery of T3 at doses comparable to safe human doses promoted new mature OL formation and myelination after SCI.

A brain-spine interface alleviating gait deficits after spinal cord injury in primates.

PubMed

Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

2016-11-10

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis. Theoretically, this strategy could also restore control over leg muscle activity for walking. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges. Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion. Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury.

Serotonin Affects Movement Gain Control in the Spinal Cord

PubMed Central

Glaser, Joshua I.; Deng, Linna; Thompson, Christopher K.; Stevenson, Ian H.; Wang, Qining; Hornby, Thomas George; Heckman, Charles J.; Kording, Konrad P.

2014-01-01

A fundamental challenge for the nervous system is to encode signals spanning many orders of magnitude with neurons of limited bandwidth. To meet this challenge, perceptual systems use gain control. However, whether the motor system uses an analogous mechanism is essentially unknown. Neuromodulators, such as serotonin, are prime candidates for gain control signals during force production. Serotonergic neurons project diffusely to motor pools, and, therefore, force production by one muscle should change the gain of others. Here we present behavioral and pharmaceutical evidence that serotonin modulates the input–output gain of motoneurons in humans. By selectively changing the efficacy of serotonin with drugs, we systematically modulated the amplitude of spinal reflexes. More importantly, force production in different limbs interacts systematically, as predicted by a spinal gain control mechanism. Psychophysics and pharmacology suggest that the motor system adopts gain control mechanisms, and serotonin is a primary driver for their implementation in force production. PMID:25232107

The effect of spinal curvature on the photogrammetric assessment on static balance in elderly women.

PubMed

Drzał-Grabiec, Justyna; Rachwał, Maciej; Podgórska-Bednarz, Justyna; Rykała, Justyna; Snela, Sławomir; Truszczyńska, Aleksandra; Trzaskoma, Zbigniew

2014-05-29

Involutional changes to the body in elderly patients affect the shape of the spine and the activity of postural muscles. The purpose of this study was to assess the influence of age-related changes in spinal curvature on postural balance in elderly women. The study population consisted of 90 women, with a mean age of 70 ± 8.01 years. Static balance assessments were conducted on a tensometric platform, and posturographic assessments of body posture were performed using a photogrammetric method based on the Projection Moiré method. The results obtained were analysed using the Spearman's rank correlation coefficient test. We found a statistically significant correlation between body posture and the quality of the balance system response based on the corrective function of the visual system. The shape of the spinal curvature influenced postural stability, as measured by static posturography. Improvement in the quality of the balance system response depended on corrective information from the visual system and proprioceptive information from the paraspinal muscles. The sensitivity of the balance system to the change of centre of pressure location was influenced by the direction of the change in rotation of the shoulder girdle and spine. Development of spinal curvature in the sagittal plane and maintenance of symmetry in the coronal and transverse planes are essential for correct balance control, which in turn is essential for the development of a properly proportioned locomotor system.

Infection after anterior spinal fusion for idiopathic scoliosis using the Cotrel-Dubousset-Hopf system: A clinical case series of three patients.

PubMed

Tolk, Jaap J; Willems, Paul C; Punt, Ilona M; van Rhijn, Lodewijk W; van Ooij, André

2016-01-01

Three patients with late-onset infection after multilevel instrumented anterior spinal fusion for idiopathic scoliosis, using the Cotrel-Dubousset-Hopf (CDH) system, are presented. The CDH-system is an anterior instrumentation with high biomechanical stability and rigidity, ensuring a stable primary fixation. Unlike after posterior spinal fusion, infection after anterior spinal fusion (ASF) for idiopathic scoliosis has rarely been reported. The files of three patients who developed an infection after ASF for scoliosis using the CDH-system, were reviewed. The clinical presentation and diagnostic and therapeutic options are discussed. All three patients had a late-onset infection of the CDH-system, which was difficult to diagnose because of nonspecific symptoms. Radiographs and technetium bone scan appeared to be of low value. When an abscess was present, this could accurately be diagnosed with MRI or CT imaging. Operative treatment with implant removal and antibiotic therapy was successful in all cases. Late onset infections after ASF using the CDH-system presented with few and nonspecific symptoms. The clinical presentation was mainly characterized by vague abdominal- or back-pain after an interval of normal postoperative recovery, moderately raised infection parameters and inconclusive findings with imaging modalities. As treatment, implant removal, debridement and parenteral antibiotics are recommended. It should be noted though that implant removal poses serious risks for vascular and visceral structures.

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.

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

PubMed

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

2018-01-01

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

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

PubMed

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

2012-10-15

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

Descending pathways to the spinal cord in teleosts in comparison with mammals, with special attention to rubrospinal pathways.

PubMed

Yamamoto, Naoyuki; Nakayama, Tomoya; Hagio, Hanako

2017-05-01

In this article we review descending neural pathways to the spinal cord in teleosts, compared with mammals. Descending pathways to the spinal cord are crucial in controlling various behaviors in vertebrates. The major difference between teleosts and mammals is the lack of corticospinal (or palliospinal) tracts. Other descending pathways, which originate from the brain stem, are basically identical in teleosts and mammals. This suggests the presence of common systems in the spinal motor control by higher order centers. The homologue of nucleus ruber remained unclear in teleosts until recently, and this review pays special attention to the rubrospinal tract. © 2017 Japanese Society of Developmental Biologists.

Selective deficiencies in descending inhibitory modulation in neuropathic rats: implications for enhancing noradrenergic tone.

PubMed

Patel, Ryan; Qu, Chaoling; Xie, Jennifer Y; Porreca, Frank; Dickenson, Anthony H

2018-06-22

Pontine noradrenergic neurones form part of a descending inhibitory system that influences spinal nociceptive processing. Weak or absent descending inhibition is a common feature of chronic pain patients. We examined the extent to which the descending noradrenergic system is tonically active, how control of spinal neuronal excitability is integrated into thalamic relays within sensory-discriminative projection pathways, and how this inhibitory control is altered after nerve injury. In vivo electrophysiology was performed in anaesthetised spinal nerve-ligated (SNL) and sham-operated rats to record from wide dynamic range neurones in the ventral posterolateral thalamus (VPL). In sham rats, spinal block of α2-adrenoceptors with atipamezole resulted in enhanced stimulus-evoked and spontaneous firing in the VPL, and produced conditioned place avoidance. However, in SNL rats, these conditioned avoidance behaviours were absent. Furthermore, inhibitory control of evoked neuronal responses was lost, but spinal atipamezole markedly increased spontaneous firing. Augmenting spinal noradrenergic tone in neuropathic rats with reboxetine, a selective noradrenergic reuptake inhibitor, modestly reinstated inhibitory control of evoked responses in the VPL but had no effect on spontaneous firing. By contrast, clonidine, an α2 agonist, inhibited both evoked and spontaneous firing, and exhibited increased potency in SNL rats compared with sham controls. These data suggest descending noradrenergic inhibitory pathways are tonically active in sham rats. Moreover, in neuropathic states, descending inhibitory control is diminished, but not completely absent, and distinguishes between spontaneous and evoked neuronal activity. These observations may have implications for how analgesics targeting the noradrenergic system provide relief.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

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.

The impact of routine whole spine MRI screening in the evaluation of spinal degenerative diseases.

PubMed

Kanna, Rishi Mugesh; Kamal, Younis; Mahesh, Anupama; Venugopal, Prakash; Shetty, Ajoy Prasad; Rajasekaran, S

2017-08-01

Magnetic resonance imaging (MRI) of the spine is a sensitive investigation, which not only provides detailed images of the spinal column but also adjacent spinal regions and para-vertebral organ systems. Such incidental findings (IF) can be asymptomatic but significant. The efficacy of whole spine T2 sagittal screening in providing additional information has been demonstrated in several spinal diseases but its routine use in patients with spinal degenerative diseases has not been studied. A review of 1486 consecutive T2w whole spine screening MRI performed for cervical, thoracic or lumbar spinal imaging for degenerative diseases, was performed to document the incidence and significance of asymptomatic IF in the spinal and extra-spinal regions. 236 (15.88%) patients had IF with a M:F ratio of 102:134 and the mean age being 50.3 years. Of these, spinal IF was observed in 122 (51.7%-Group A) while extra-spinal IF was present in 114 (48.3%-Group B). In Group A, 84 patients had IF in the vertebral column and 38 patients had IF in the spinal cord. IF within the spine included vertebral haemangioma (n = 60, 4.5%), diffuse vertebral marrow changes (n = 18, 1.2%), vertebral metastasis (n = 2), incidental cord myelopathy (n = 21), intradural tumour (n = 7), and others. 33 patients required surgical intervention of the IF (2.2%). In Group B, pelvic IF were most prevalent (n = 79, 5.3%) followed by retro-peritoneal abdominal IF in 22 (1.48%) and intra-cranial IF in 9 (0.60%). 32 (2.1%) of these pathologies required further specialist medical or surgical evaluation. Routine T2 whole spine screening MRI identified 15.8% IF of the spinal and extra-spinal regions. 65 patients (4.3%) required either spine surgical intervention or other specialist care. Considering the potential advantages in identifying significant IF and the minimal extra time spent to perform whole spine screening, its application can be considered to be incorporated in routine imaging of spinal degenerative diseases.

Spinally projecting preproglucagon axons preferentially innervate sympathetic preganglionic neurons

PubMed Central

Llewellyn-Smith, I.J.; Marina, N.; Manton, R.N.; Reimann, F.; Gribble, F.M.; Trapp, S.

2015-01-01

Glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarius (NTS) and medullary reticular formation, produce GLP-1. In transgenic mice expressing glucagon promoter-driven yellow fluorescent protein (YFP), these brainstem PPG neurons project to many central autonomic regions where GLP-1 receptors are expressed. The spinal cord also contains GLP-1 receptor mRNA but the distribution of spinal PPG axons is unknown. Here, we used two-color immunoperoxidase labeling to examine PPG innervation of spinal segments T1–S4 in YFP-PPG mice. Immunoreactivity for YFP identified spinal PPG axons and perikarya. We classified spinal neurons receiving PPG input by immunoreactivity for choline acetyltransferase (ChAT), nitric oxide synthase (NOS) and/or Fluorogold (FG) retrogradely transported from the peritoneal cavity. FG microinjected at T9 defined cell bodies that supplied spinal PPG innervation. The deep dorsal horn of lower lumbar cord contained YFP-immunoreactive neurons. Non-varicose, YFP-immunoreactive axons were prominent in the lateral funiculus, ventral white commissure and around the ventral median fissure. In T1–L2, varicose, YFP-containing axons closely apposed many ChAT-immunoreactive sympathetic preganglionic neurons (SPN) in the intermediolateral cell column (IML) and dorsal lamina X. In the sacral parasympathetic nucleus, about 10% of ChAT-immunoreactive preganglionic neurons received YFP appositions, as did occasional ChAT-positive motor neurons throughout the rostrocaudal extent of the ventral horn. YFP appositions also occurred on NOS-immunoreactive spinal interneurons and on spinal YFP-immunoreactive neurons. Injecting FG at T9 retrogradely labeled many YFP-PPG cell bodies in the medulla but none of the spinal YFP-immunoreactive neurons. These results show that brainstem PPG neurons innervate spinal autonomic and somatic motor neurons. The distributions of spinal PPG axons and spinal GLP-1 receptors correlate well. SPN receive the densest PPG innervation. Brainstem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to SPN or interneurons. PMID:25450967

Preliminary development of augmented reality systems for spinal surgery

NASA Astrophysics Data System (ADS)

Nguyen, Nhu Q.; Ramjist, Joel M.; Jivraj, Jamil; Jakubovic, Raphael; Deorajh, Ryan; Yang, Victor X. D.

2017-02-01

Surgical navigation has been more actively deployed in open spinal surgeries due to the need for improved precision during procedures. This is increasingly difficult in minimally invasive surgeries due to the lack of visual cues caused by smaller exposure sites, and increases a surgeon's dependence on their knowledge of anatomical landmarks as well as the CT or MRI images. The use of augmented reality (AR) systems and registration technologies in spinal surgeries could allow for improvements to techniques by overlaying a 3D reconstruction of patient anatomy in the surgeon's field of view, creating a mixed reality visualization. The AR system will be capable of projecting the 3D reconstruction onto a field and preliminary object tracking on a phantom. Dimensional accuracy of the mixed media will also be quantified to account for distortions in tracking.

The Incidence of Adjacent Segment Degeneration after the Use of a Versatile Dynamic Hybrid Stabilization Device in Lumbar Stenosis: Results of a 5–8-Year Follow-up

PubMed Central

Dobran, Mauro; Esposito, Domenico Paolo; Gladi, Maurizio; Scerrati, Massimo; Iacoangeli, Maurizio

2018-01-01

Study Design Retrospective study with long-term follow-up. Purpose To evaluate the long-term incidence of adjacent segment degeneration (ASD) and clinical outcomes in a consecutive series of patients who underwent spinal decompression associated with dynamic or hybrid stabilization with a Flex+TM stabilization system (SpineVision, Antony, France) for lumbar spinal stenosis. Overview of Literature The incidence of ASD and clinical outcomes following dynamic or hybrid stabilization with the Flex+TM system used for lumbar spinal stenosis have not been well investigated. Methods Twenty-one patients with lumbar stenosis and probable post-decompressive spinal instability underwent decompressive laminectomy followed by spinal stabilization using the Flex+TM stabilization system. The indication for a mono-level dynamic stabilization was a preoperative magnetic resonance imaging (MRI) demonstrating evidence of severe disc disease associated with severe spinal stenosis. The hybrid stabilization (rigid-dynamic) system was used for multilevel laminectomies with associated initial degenerative scoliosis, first-grade spondylolisthesis, or rostral pathology. Results The improvement in Visual Analog Scale and Oswestry Disability Index scores at follow-up were statistically significant (p<0.0001 and p<0.0001, respectively). At the 5–8-year follow-up, clinical examination, MRI, and X-ray findings showed an ASD complication with pain and disability in one of 21 patients. The clinical outcomes were similar in patients treated with dynamic or hybrid fixation. Conclusions Patients treated with laminectomy and Flex+TM stabilization presented a satisfactory clinical outcome after 5–8 years of follow-up, and ASD incidence in our series was 4.76% (one patient out of 21). We are aware that this is a small series, but our long-term follow-up may be sufficient to contribute to the expanding body of literature on the development of symptomatic ASD associated with dynamic or hybrid fixation. PMID:29713407

Modeling of Spinal Column of Seated Human Body under Exposure to Whole-Body Vibration

NASA Astrophysics Data System (ADS)

Tamaoki, Gen; Yoshimura, Takuya; Kuriyama, Kaoru; Nakai, Kazuma

In vehicle systems occupational drivers might expose themselves to vibration for a long time. This may cause illness of the spinal column such as low back pain. Therefore, it is necessary to evaluate the influence of vibration to the spinal column. Thus the modeling of seated human body is conducted in order to evaluate the effect of whole-body vibration to the spinal column. This model has the spinal column and the support structures such as the muscles of the back and the abdomen. The spinal column is made by the vertebrae and the intervertebral disks that are considered the rigid body and the rotational spring and damper respectively. The parameter of this model is decided by the literature and the body type of the subject with respect to the mass and the model structure. And stiffness and damping parameters are searched by fitting the model simulation results to the experimental measured data with respect to the vibration transmissibilities from the seat surface to the spinal column and the head and with respect to the driving-point apparent mass. In addition, the natural modes of the model compare with the result of experimental modal analysis. The influence of the abdomen and the muscles of the back are investigated by comparing three models with respect to above vibration characteristics. Three model are the proposed model, the model that has the spinal column and the model that has the muscles of the back in addition to the spinal column.

[Clinical application of super-link system theory in spinal cord injury patients during rehabilitation stage].

PubMed

Chen, Hsiao-Yu

2008-04-01

The purpose of this paper is to introduce Super-Link System Theory, which is a theory of spinal cord injury rehabilitation. This theory has been developed using the grounded theory research method. By explaining the procedure for establishing a super-link system the paper explains the complex structure of this theory. Super-Link System Theory emphasizes that rehabilitation nurses 'build up their interpersonal relationships' with clients, family caregivers, the interdisciplinary team, and the community, and attempt to 'establish links' among them. They know these links have to be made with appropriate 'timing', and must be able to access the appropriate people when necessary. Super-link systems include the following four links: link to client with spinal cord injury, link to family caregiver, link to interdisciplinary rehabilitation team, and link to community. It can enable rehabilitation nurses to provide a better quality of nursing care to clients and their family caregivers, as well as promote their professional position in the interdisciplinary rehabilitation team.

Spinal Cord Injury Model Systems: Review of Program and National Database From 1970 to 2015.

PubMed

Chen, Yuying; DeVivo, Michael J; Richards, J Scott; SanAgustin, Theresa B

2016-10-01

The Spinal Cord Injury Model Systems (SCIMS) centers have provided continuous, comprehensive multidisciplinary care for persons with spinal cord injury (SCI) in the United States since their inception in 1970. In addition, the research conducted and the analysis of data collected at these centers facilitate advances in the care and the overall quality of life for people with SCI. Over the past 45 years, the SCIMS program and National Spinal Cord Injury Database (NSCID) have undergone major revisions, which must be recognized in the planning, conduct, and interpretation of SCIMS research to prevent misinterpretation of findings. Therefore, we provide herein a brief review of the SCIMS program and the associated NSCID throughout its history, emphasizing changes and accomplishments within the past 15 years, to facilitate a better understanding and interpretation of the data presented in SCIMS research publications, including the articles published in this special issue of the Archives. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

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.

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.

Treatment planning for spinal radiosurgery : A competitive multiplatform benchmark challenge.

PubMed

Moustakis, Christos; Chan, Mark K H; Kim, Jinkoo; Nilsson, Joakim; Bergman, Alanah; Bichay, Tewfik J; Palazon Cano, Isabel; Cilla, Savino; Deodato, Francesco; Doro, Raffaela; Dunst, Jürgen; Eich, Hans Theodor; Fau, Pierre; Fong, Ming; Haverkamp, Uwe; Heinze, Simon; Hildebrandt, Guido; Imhoff, Detlef; de Klerck, Erik; Köhn, Janett; Lambrecht, Ulrike; Loutfi-Krauss, Britta; Ebrahimi, Fatemeh; Masi, Laura; Mayville, Alan H; Mestrovic, Ante; Milder, Maaike; Morganti, Alessio G; Rades, Dirk; Ramm, Ulla; Rödel, Claus; Siebert, Frank-Andre; den Toom, Wilhelm; Wang, Lei; Wurster, Stefan; Schweikard, Achim; Soltys, Scott G; Ryu, Samuel; Blanck, Oliver

2018-05-25

To investigate the quality of treatment plans of spinal radiosurgery derived from different planning and delivery systems. The comparisons include robotic delivery and intensity modulated arc therapy (IMAT) approaches. Multiple centers with equal systems were used to reduce a bias based on individual's planning abilities. The study used a series of three complex spine lesions to maximize the difference in plan quality among the various approaches. Internationally recognized experts in the field of treatment planning and spinal radiosurgery from 12 centers with various treatment planning systems participated. For a complex spinal lesion, the results were compared against a previously published benchmark plan derived for CyberKnife radiosurgery (CKRS) using circular cones only. For two additional cases, one with multiple small lesions infiltrating three vertebrae and a single vertebra lesion treated with integrated boost, the results were compared against a benchmark plan generated using a best practice guideline for CKRS. All plans were rated based on a previously established ranking system. All 12 centers could reach equality (n = 4) or outperform (n = 8) the benchmark plan. For the multiple lesions and the single vertebra lesion plan only 5 and 3 of the 12 centers, respectively, reached equality or outperformed the best practice benchmark plan. However, the absolute differences in target and critical structure dosimetry were small and strongly planner-dependent rather than system-dependent. Overall, gantry-based IMAT with simple planning techniques (two coplanar arcs) produced faster treatments and significantly outperformed static gantry intensity modulated radiation therapy (IMRT) and multileaf collimator (MLC) or non-MLC CKRS treatment plan quality regardless of the system (mean rank out of 4 was 1.2 vs. 3.1, p = 0.002). High plan quality for complex spinal radiosurgery was achieved among all systems and all participating centers in this planning challenge. This study concludes that simple IMAT techniques can generate significantly better plan quality compared to previous established CKRS benchmarks.

Visualizing the spinal neuronal dynamics of locomotion

NASA Astrophysics Data System (ADS)

Subramanian, Kalpathi R.; Bashor, D. P.; Miller, M. T.; Foster, J. A.

2004-06-01

Modern imaging and simulation techniques have enhanced system-level understanding of neural function. In this article, we present an application of interactive visualization to understanding neuronal dynamics causing locomotion of a single hip joint, based on pattern generator output of the spinal cord. Our earlier work visualized cell-level responses of multiple neuronal populations. However, the spatial relationships were abstract, making communication with colleagues difficult. We propose two approaches to overcome this: (1) building a 3D anatomical model of the spinal cord with neurons distributed inside, animated by the simulation and (2) adding limb movements predicted by neuronal activity. The new system was tested using a cat walking central pattern generator driving a pair of opposed spinal motoneuron pools. Output of opposing motoneuron pools was combined into a single metric, called "Net Neural Drive", which generated angular limb movement in proportion to its magnitude. Net neural drive constitutes a new description of limb movement control. The combination of spatial and temporal information in the visualizations elegantly conveys the neural activity of the output elements (motoneurons), as well as the resulting movement. The new system encompasses five biological levels of organization from ion channels to observed behavior. The system is easily scalable, and provides an efficient interactive platform for rapid hypothesis testing.

Comparative Study Between Cobalt Chrome and Titanium Alloy Rods for Multilevel Spinal Fusion: Proximal Junctional Kyphosis More Frequently Occurred in Patients Having Cobalt Chrome Rods.

PubMed

Han, Sanghyun; Hyun, Seung-Jae; Kim, Ki-Jeong; Jahng, Tae-Ahn; Kim, Hyun-Jib

2017-07-01

The use of titanium alloy (Ti) rods is frequently associated with rod fracture after spinal fixation. To address this issue, cobalt chrome (CoCr) rods, which are advantageous because of their greater strength and resistance to fatigue relative to Ti rods, have been introduced. The purpose of the present study was to compare radiographic outcomes after the use of Ti versus CoCr rods in a matched cohort of patients undergoing posterior spinal fusion for treatment of spinal instability. We retrospectively reviewed data from patients who had undergone spinal fusion involving more than 3 levels at a single institution between 2004 and 2015. Patients were matched for age, diagnosis, 3-column osteotomy, levels fused, and T score. Fifty patients with Ti rods were identified and appropriately matched to 50 consecutive patients with CoCr rods. The distributions of age at surgery, sex, diagnosis, 3-column osteotomy, levels fused, number of patients with previous surgical procedures, and T score did not significantly differ between the 2 groups. However, there were significant differences in length of follow-up (CoCr, 25.0 vs. Ti, 28.5 months; P < 0.001), fusion rate (CoCr, 45 [90%] vs. Ti, 33 [66%]; P = 0.004), occurrence of rod breakage (CoCr, 0 vs. T, 8 [16%]; P = 0.006), and junctional kyphosis (CoCr, 24 [46%] vs. Ti, 9 [18%]; P = 0.003). Our findings indicate that the use of CoCr rods is effective in ensuring stability of the posterior spinal construct and accomplishment of spinal fusion. Furthermore, our results indicate that junctional kyphosis may occur more frequently in CoCr systems than in Ti systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Metaplasticity and behavior: how training and inflammation affect plastic potential within the spinal cord and recovery after injury

PubMed Central

Grau, James W.; Huie, J. Russell; Lee, Kuan H.; Hoy, Kevin C.; Huang, Yung-Jen; Turtle, Joel D.; Strain, Misty M.; Baumbauer, Kyle M.; Miranda, Rajesh M.; Hook, Michelle A.; Ferguson, Adam R.; Garraway, Sandra M.

2014-01-01

Research has shown that spinal circuits have the capacity to adapt in response to training, nociceptive stimulation and peripheral inflammation. These changes in neural function are mediated by physiological and neurochemical systems analogous to those that support plasticity within the hippocampus (e.g., long-term potentiation and the NMDA receptor). As observed in the hippocampus, engaging spinal circuits can have a lasting impact on plastic potential, enabling or inhibiting the capacity to learn. These effects are related to the concept of metaplasticity. Behavioral paradigms are described that induce metaplastic effects within the spinal cord. Uncontrollable/unpredictable stimulation, and peripheral inflammation, induce a form of maladaptive plasticity that inhibits spinal learning. Conversely, exposure to controllable or predictable stimulation engages a form of adaptive plasticity that counters these maladaptive effects and enables learning. Adaptive plasticity is tied to an up-regulation of brain derived neurotrophic factor (BDNF). Maladaptive plasticity is linked to processes that involve kappa opioids, the metabotropic glutamate (mGlu) receptor, glia, and the cytokine tumor necrosis factor (TNF). Uncontrollable nociceptive stimulation also impairs recovery after a spinal contusion injury and fosters the development of pain (allodynia). These adverse effects are related to an up-regulation of TNF and a down-regulation of BDNF and its receptor (TrkB). In the absence of injury, brain systems quell the sensitization of spinal circuits through descending serotonergic fibers and the serotonin 1A (5HT 1A) receptor. This protective effect is blocked by surgical anesthesia. Disconnected from the brain, intracellular Cl- concentrations increase (due to a down-regulation of the cotransporter KCC2), which causes GABA to have an excitatory effect. It is suggested that BDNF has a restorative effect because it up-regulates KCC2 and re-establishes GABA-mediated inhibition. PMID:25249941

Development of less invasive neuromuscular electrical stimulation model for motor therapy in rodents

PubMed Central

Kanchiku, Tsukasa; Kato, Yoshihiko; Suzuki, Hidenori; Imajo, Yasuaki; Yoshida, Yuichiro; Moriya, Atsushi; Taguchi, Toshihiko; Jung, Ranu

2012-01-01

Background Combination therapy is essential for functional repairs of the spinal cord. Rehabilitative therapy can be considered as the key for reorganizing the nervous system after spinal cord regeneration therapy. Functional electrical stimulation has been used as a neuroprosthesis in quadriplegia and can be used for providing rehabilitative therapy to tap the capability for central nervous system reorganization after spinal cord regeneration therapy. Objective To develop a less invasive muscular electrical stimulation model capable of being combined with spinal cord regeneration therapy especially for motor therapy in the acute stage after spinal cord injury. Methods The tibialis anterior and gastrocnemius motor points were identified in intact anesthetized adult female Fischer rats, and stimulation needle electrodes were percutaneously inserted into these points. Threshold currents for visual twitches were obtained upon stimulation using pulses of 75 or 8 kHz for 200 ms. Biphasic pulse widths of 20, 40, 80, 100, 300, and 500 µs per phase were used to determine strength–duration curves. Using these parameters and previously obtained locomotor electromyogram data, stimulations were performed on bilateral joint muscle pairs to produce reciprocal flexion/extension movements of the ankle for 15 minutes while three-dimensional joint kinematics were assessed. Results Rhythmic muscular electrical stimulation with needle electrodes was successfully done, but decreased range of motion (ROM) over time. High-frequency and high-amplitude stimulation was also shown to be effective in alleviating decreases in ROM due to muscle fatigue. Conclusions This model will be useful for investigating the ability of rhythmic muscular electrical stimulation therapy to promote motor recovery, in addition to the efficacy of combining treatments with spinal cord regeneration therapy after spinal cord injuries. PMID:22507026

Spinal primitives and intra-spinal micro-stimulation (ISMS) based prostheses: a neurobiological perspective on the “known unknowns” in ISMS and future prospects

PubMed Central

Giszter, Simon F.

2015-01-01

The current literature on Intra-Spinal Micro-Stimulation (ISMS) for motor prostheses is reviewed in light of neurobiological data on spinal organization, and a neurobiological perspective on output motor modularity, ISMS maps, stimulation combination effects, and stability. By comparing published data in these areas, the review identifies several gaps in current knowledge that are crucial to the development of effective intraspinal neuroprostheses. Gaps can be categorized into a lack of systematic and reproducible details of: (a) Topography and threshold for ISMS across the segmental motor system, the topography of autonomic recruitment by ISMS, and the coupling relations between these two types of outputs in practice. (b) Compositional rules for ISMS motor responses tested across the full range of the target spinal topographies. (c) Rules for ISMS effects' dependence on spinal cord state and neural dynamics during naturally elicited or ISMS triggered behaviors. (d) Plasticity of the compositional rules for ISMS motor responses, and understanding plasticity of ISMS topography in different spinal cord lesion states, disease states, and following rehabilitation. All these knowledge gaps to a greater or lesser extent require novel electrode technology in order to allow high density chronic recording and stimulation. The current lack of this technology may explain why these prominent gaps in the ISMS literature currently exist. It is also argued that given the “known unknowns” in the current ISMS literature, it may be prudent to adopt and develop control schemes that can manage the current results with simple superposition and winner-take-all interactions, but can also incorporate the possible plastic and stochastic dynamic interactions that may emerge in fuller analyses over longer terms, and which have already been noted in some simpler model systems. PMID:25852454

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

Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization

PubMed Central

Corleto, Jose A.; Bravo-Hernández, Mariana; Kamizato, Kota; Kakinohana, Osamu; Santucci, Camila; Navarro, Michael R.; Platoshyn, Oleksandr; Cizkova, Dasa; Lukacova, Nadezda; Taylor, Julian; Marsala, Martin

2015-01-01

The development of spinal hyper-reflexia as part of the spasticity syndrome represents one of the major complications associated with chronic spinal traumatic injury (SCI). The primary mechanism leading to progressive appearance of muscle spasticity is multimodal and may include loss of descending inhibitory tone, alteration of segmental interneuron-mediated inhibition and/or increased reflex activity to sensory input. Here, we characterized a chronic thoracic (Th 9) complete transection model of muscle spasticity in Sprague-Dawley (SD) rats. Isoflurane-anesthetized rats received a Th9 laminectomy and the spinal cord was transected using a scalpel blade. After the transection the presence of muscle spasticity quantified as stretch and cutaneous hyper-reflexia was identified and quantified as time-dependent changes in: i) ankle-rotation-evoked peripheral muscle resistance (PMR) and corresponding electromyography (EMG) activity, ii) Hoffmann reflex, and iii) EMG responses in gastrocnemius muscle after paw tactile stimulation for up to 8 months after injury. To validate the clinical relevance of this model, the treatment potency after systemic treatment with the clinically established anti-spastic agents baclofen (GABAB receptor agonist), tizanidine (α2-adrenergic agonist) and NGX424 (AMPA receptor antagonist) was also tested. During the first 3 months post spinal transection, a progressive increase in ankle rotation-evoked muscle resistance, Hoffmann reflex amplitude and increased EMG responses to peripherally applied tactile stimuli were consistently measured. These changes, indicative of the spasticity syndrome, then remained relatively stable for up to 8 months post injury. Systemic treatment with baclofen, tizanidine and NGX424 led to a significant but transient suppression of spinal hyper-reflexia. These data demonstrate that a chronic Th9 spinal transection model in adult SD rat represents a reliable experimental platform to be used in studying the pathophysiology of chronic spinal injury-induced spasticity. In addition a consistent anti-spastic effect measured after treatment with clinically effective anti-spastic agents indicate that this model can effectively be used in screening new anti-spasticity compounds or procedures aimed at modulating chronic spinal trauma-associated muscle spasticity. PMID:26713446

Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat.

PubMed

Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

2007-04-01

Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor kappaB (NF-kappaB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-kappaB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-kappaB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-kappaB super- repressor IkappaBalpha resulted in an inhibition of the NF-kappaB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IkappaBalpha overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-kappaB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-kappaB pathway in the development of neuropathic pain after peripheral nerve injury.

Protocol of a prospective cohort study of the effect of different methods of drainage of neuropathic bladder on occurrence of symptomatic urinary infection, and adverse events related to the urinary drainage system in spinal cord injury patients

PubMed Central

Vaidyanathan, Subramanian; Soni, Bhakul M; Gurpreet, Singh; Mansour, Paul; Hughes, Peter L; Oo, Tun; Sett, Pradipkumar; Parsons, Keith F; Davies, John C

2001-01-01

Background To present a protocol of a prospective, cohort study in which four groups of spinal cord injury (SCI) patients will participate. (Patients with indwelling urethral catheter; patients who perform intermittent catheterisation without wearing a penile sheath; patients who perform intermittent catheterisation and wear penile sheath as well; and patients with penile sheath drainage). Objectives (1) What is the incidence of symptomatic urinary infection in men with spinal cord injury who use different types of bladder drainage? (2) Which are predisposing factors for the occurrence of symptomatic urinary infection in men with spinal cord injury who practise different methods of bladder drainage? (3) What is the incidence of catheter and urinary drainage system-related adverse events in the four groups of SCI patients? Patients The criteria for inclusion are as follow: (1) Male patients with neuropathic bladder due to spinal cord injury, who are registered with the Regional Spinal Injuries Centre, Southport, England. (2) Age: 18 years or above. (3) Patients who are willing to give informed consent for participation in the study. (4) Patients willing to be contacted every two weeks by a staff of the spinal unit for 36 months. (5) Patients who are willing to maintain an accurate record of adverse events related to urinary catheter and urinary drainage system and predisposing factors for the occurrence of symptomatic urinary infection. (6) Patients, who are stabilised in a particular method of bladder drainage, and therefore, unlikely to make a permanent change in the method of bladder drainage (e.g. from penile sheath drainage to the use of long-term indwelling catheter) during a foreseeable future. Methods The participants will be observed for a period of 36 months. A staff of the spinal injuries unit will contact the participants by telephone every two weeks on a mutually agreed day and time. The information obtained during this standardised telephonic interview conducted once in two weeks will be entered in a database. When a participant develops symptom(s) suggestive of urinary infection, he will undergo urine and blood tests, and imaging studies of the urinary tract. Conclusion This study will provide information regarding the occurrence of symptomatic urinary infection, predisposing factors for development of urinary infection, and adverse events related to urinary catheter and urinary drainage system in SCI patients using different methods of bladder drainage. PMID:11734072

Standardized way for imaging of the sagittal spinal balance.

PubMed

Morvan, Gérard; Mathieu, Philippe; Vuillemin, Valérie; Guerini, Henri; Bossard, Philippe; Zeitoun, Frédéric; Wybier, Marc

2011-09-01

Nowadays, conventional or digitalized teleradiography remains the most commonly used tool for the study of the sagittal balance, sometimes with secondary digitalization. The irradiation given by this technique is important and the photographic results are often poor. Some radiographic tables allow the realization of digitalized spinal radiographs by simultaneous translation of X-ray tube and receptor. EOS system is a new, very low dose system which gives good quality images, permits a simultaneous acquisition of upright frontal and sagittal views, is able to cover in the same time the spine and the lower limbs and study the axial plane on 3D envelope reconstructions. In the future, this low dose system should take a great place in the study of the pelvispinal balance. On the lateral view, several pelvic (incidence, pelvic tilt, sacral slope) and spinal (lumbar lordosis, thoracic kyphosis, Th9 sagittal offset, C7 plumb line) parameters are drawn to define the pelvispinal balance. All are interdependent. Pelvic incidence is an individual anatomic characteristic that corresponds to the "thickness" of the pelvis and governs the spinal balance. Pelvis and spine, in a harmonious whole, can be compared to an accordion, more or less compressed or stretched.

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.

Feasibility of a Modified E-PASS and POSSUM System for Postoperative Risk Assessment in Patients with Spinal Disease.

PubMed

Chun, Dong Hyun; Kim, Do Young; Choi, Sun Kyu; Shin, Dong Ah; Ha, Yoon; Kim, Keung Nyun; Yoon, Do Heum; Yi, Seong

2018-04-01

This retrospective case control study aimed to evaluate the feasibility of using Estimation of Physiological Ability and Surgical Stress (E-PASS) and Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM) systems in patients undergoing spinal surgical procedures. Degenerative spine disease has increased in incidence in aging societies, as has the number of older adult patients undergoing spinal surgery. Many older adults are at a high surgical risk because of comorbidity and poor general health. We retrospectively reviewed 217 patients who had undergone spinal surgery at a single tertiary care. We investigated complications within 1 month after surgery. Criteria for both skin incision in E-PASS and operation magnitude in the POSSUM system were modified to fit spine surgery. We calculated the E-PASS and POSSUM scores for enrolled patients, and investigated the relationship between postoperative complications and both surgical risk scoring systems. To reinforce the predictive ability of the E-PASS system, we adjusted equations and developed modified E-PASS systems. The overall complication rate for spinal surgery was 22.6%. Forty-nine patients experienced 58 postoperative complications. Nineteen major complications, including hematoma, deep infection, pleural effusion, progression of weakness, pulmonary edema, esophageal injury, myocardial infarction, pneumonia, reoperation, renal failure, sepsis, and death, occurred in 17 patients. The area under the receiver operating characteristic curve (AUC) for predicted postoperative complications after spine surgery was 0.588 for E-PASS and 0.721 for POSSUM. For predicted major postoperative complications, the AUC increased to 0.619 for E-PASS and 0.842 for POSSUM. The AUC of the E-PASS system increased from 0.588 to 0.694 with the Modified E-PASS equation. The POSSUM system may be more useful than the E-PASS system for estimating postoperative surgical risk in patients undergoing spine surgery. The preoperative risk scores of E-PASS and POSSUM can be useful for predicting postoperative major complications. To enhance the predictability of the scoring systems, using of modified equations based on spine surgery-specific factors may help ensure surgical outcomes and patient safety. Copyright © 2017. Published by Elsevier Inc.

Controlling specific locomotor behaviors through multidimensional monoaminergic modulation of spinal circuitries

PubMed Central

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

2012-01-01

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

Karolinska institutet 200-year anniversary. Symposium on traumatic injuries in the nervous system: injuries to the spinal cord and peripheral nervous system - injuries and repair, pain problems, lesions to brachial plexus.

PubMed

Sköld, Mattias K; Svensson, Mikael; Tsao, Jack; Hultgren, Thomas; Landegren, Thomas; Carlstedt, Thomas; Cullheim, Staffan

2011-01-01

The Karolinska Institutet 200-year anniversary symposium on injuries to the spinal cord and peripheral nervous system gathered expertise in the spinal cord, spinal nerve, and peripheral nerve injury field spanning from molecular prerequisites for nerve regeneration to clinical methods in nerve repair and rehabilitation. The topics presented at the meeting covered findings on adult neural stem cells that when transplanted to the hypoglossal nucleus in the rat could integrate with its host and promote neuron survival. Studies on vascularization after intraspinal replantation of ventral nerve roots and microarray studies in ventral root replantation as a tool for mapping of biological patterns typical for neuronal regeneration were discussed. Different immune molecules in neurons and glia and their very specific roles in synapse plasticity after injury were presented. Novel strategies in repair of injured peripheral nerves with ethyl-cyanoacrylate adhesive showed functional recovery comparable to that of conventional epineural sutures. Various aspects on surgical techniques which are available to improve function of the limb, once the nerve regeneration after brachial plexus lesions and repair has reached its limit were presented. Moreover, neurogenic pain after amputation and its treatment with mirror therapy were shown to be followed by dramatic decrease in phantom limb pain. Finally clinical experiences on surgical techniques to repair avulsed spinal nerve root and the motoric as well as sensoric regain of function were presented.

Karolinska Institutet 200-Year Anniversary. Symposium on Traumatic Injuries in the Nervous System: Injuries to the Spinal Cord and Peripheral Nervous System – Injuries and Repair, Pain Problems, Lesions to Brachial Plexus

PubMed Central

Sköld, Mattias K.; Svensson, Mikael; Tsao, Jack; Hultgren, Thomas; Landegren, Thomas; Carlstedt, Thomas; Cullheim, Staffan

2011-01-01

The Karolinska Institutet 200-year anniversary symposium on injuries to the spinal cord and peripheral nervous system gathered expertise in the spinal cord, spinal nerve, and peripheral nerve injury field spanning from molecular prerequisites for nerve regeneration to clinical methods in nerve repair and rehabilitation. The topics presented at the meeting covered findings on adult neural stem cells that when transplanted to the hypoglossal nucleus in the rat could integrate with its host and promote neuron survival. Studies on vascularization after intraspinal replantation of ventral nerve roots and microarray studies in ventral root replantation as a tool for mapping of biological patterns typical for neuronal regeneration were discussed. Different immune molecules in neurons and glia and their very specific roles in synapse plasticity after injury were presented. Novel strategies in repair of injured peripheral nerves with ethyl-cyanoacrylate adhesive showed functional recovery comparable to that of conventional epineural sutures. Various aspects on surgical techniques which are available to improve function of the limb, once the nerve regeneration after brachial plexus lesions and repair has reached its limit were presented. Moreover, neurogenic pain after amputation and its treatment with mirror therapy were shown to be followed by dramatic decrease in phantom limb pain. Finally clinical experiences on surgical techniques to repair avulsed spinal nerve root and the motoric as well as sensoric regain of function were presented. PMID:21629875

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.

A multimedia electronic patient record (ePR) system for image-assisted minimally invasive spinal surgery.

PubMed

Documet, Jorge; Le, Anh; Liu, Brent; Chiu, John; Huang, H K

2010-05-01

This paper presents the concept of bridging the gap between diagnostic images and image-assisted surgical treatment through the development of a one-stop multimedia electronic patient record (ePR) system that manages and distributes the real-time multimodality imaging and informatics data that assists the surgeon during all clinical phases of the operation from planning Intra-Op to post-care follow-up. We present the concept of this multimedia ePR for surgery by first focusing on image-assisted minimally invasive spinal surgery as a clinical application. Three clinical phases of minimally invasive spinal surgery workflow in Pre-Op, Intra-Op, and Post-Op are discussed. The ePR architecture was developed based on the three-phased workflow, which includes the Pre-Op, Intra-Op, and Post-Op modules and four components comprising of the input integration unit, fault-tolerant gateway server, fault-tolerant ePR server, and the visualization and display. A prototype was built and deployed to a minimally invasive spinal surgery clinical site with user training and support for daily use. A step-by-step approach was introduced to develop a multimedia ePR system for imaging-assisted minimally invasive spinal surgery that includes images, clinical forms, waveforms, and textual data for planning the surgery, two real-time imaging techniques (digital fluoroscopic, DF) and endoscope video images (Endo), and more than half a dozen live vital signs of the patient during surgery. Clinical implementation experiences and challenges were also discussed.

Challenges of transcutaneous laser application for the potential of photobiomodulation of the spinal cord at the scale of a large companion animal

NASA Astrophysics Data System (ADS)

Piao, Daqing; Sypniewski, Lara A.; Bartels, Kenneth E.

2017-02-01

Photobiomodulation (PBM) has been used successfully for the treatment of nervous system and has been demonstrated in the rodent model. In contrast, the percutaneous use of PBM to treat spinal cord of companion animals is expected to be challenging due to the significant attenuation of light energy as it travels through the thick and heterogeneous layers of tissue and bone to reach the level of the spinal cord. This pilot study was performed on a cadaverous dog to determine if the recommended bio-stimulatory treatment dose can be delivered to the spinal canal via percutaneous application of a clinically acceptable surface dose. The dose reaching the spinal canal after percutaneous application was measured at 980nm by using a miniature photo-diode sensor with a dose-response sensitivity of 1V per 1mW/cm2 dose and a 2mm spherical isotropic fiber-optical diffusor probe. The two sensors were embedded in different longitudinal positions along the dorsal portion of the spinal canal just below the soft tissues and vertebral processes in a 40lbs cadaverous dog. The spinal cord was then accessed via a hemilaminectomy. Once embedded in the target tissue, 1W-10 W surface irradiation was applied. At the T12/13 and T13/L1 intervertebral disc positions, photo-diode sensors detected the intra-spinal dose above the noise floor at the 10W surface dose. A narrow treatment window for percutaneous PBM in large dog may exist only for the shallowest segment of the spinal cord, which may be important to avoid potential collateral photothermal effects. Works for simultaneous multi-site intra-spinal measurements are on-going.

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.

Sudden-onset paraplegia during pregnancy caused by haemorrhage in a spinal cord haemangioblastoma: A case report.

PubMed

Gormeli, Cemile Ayse; Sarac, Kaya; Ozdemir, Zeynep Maras; Gormeli, Gokay; Kahraman, Aysegul Sagir; Kahraman, Bayram; Oztanir, Mustafa Namik; Karadag, Nese

2016-09-01

Spinal cord haemangioblastomas are rare central nervous systems tumours, and haemorrhage.It is an uncommon occurance. We report a 28-year-old pregnant patient who presented with paraplegia due to acute haemorrhage of a spinal haemangioblastoma. Magnetic resonance imaging showed extensive syrinx cavities, an intramedullary lesion at the T4-T5 spinal cord level e, and a subarachnoid haemorrhage. Digital subtraction angiography showed the feeding artery and dilated tortuous draining vein within the dural sac. The lesion was deemed a haemangioblastoma. The histopathological examination confirmed the diagnosis. Postoperatively, the paraplegia improved and the patient was able to walk within 2 weeks. Imaging is important for early diagnosis to prevent patients persistent neurological deficits.

Acute intermittent hypoxia and rehabilitative training following cervical spinal injury alters neuronal hypoxia- and plasticity-associated protein expression.

PubMed

Hassan, Atiq; Arnold, Breanna M; Caine, Sally; Toosi, Behzad M; Verge, Valerie M K; Muir, Gillian D

2018-01-01

One of the most promising approaches to improve recovery after spinal cord injury (SCI) is the augmentation of spontaneously occurring plasticity in uninjured neural pathways. Acute intermittent hypoxia (AIH, brief exposures to reduced O2 levels alternating with normal O2 levels) initiates plasticity in respiratory systems and has been shown to improve recovery in respiratory and non-respiratory spinal systems after SCI in experimental animals and humans. Although the mechanism by which AIH elicits its effects after SCI are not well understood, AIH is known to alter protein expression in spinal neurons in uninjured animals. Here, we examine hypoxia- and plasticity-related protein expression using immunofluorescence in spinal neurons in SCI rats that were treated with AIH combined with motor training, a protocol which has been demonstrated to improve recovery of forelimb function in this lesion model. Specifically, we assessed protein expression in spinal neurons from animals with incomplete cervical SCI which were exposed to AIH treatment + motor training either for 1 or 7 days. AIH treatment consisted of 10 episodes of AIH: (5 min 11% O2: 5 min 21% O2) for 7 days beginning at 4 weeks post-SCI. Both 1 or 7 days of AIH treatment + motor training resulted in significantly increased expression of the transcription factor hypoxia-inducible factor-1α (HIF-1α) relative to normoxia-treated controls, in neurons both proximal (cervical) and remote (lumbar) to the SCI. All other markers examined were significantly elevated in the 7 day AIH + motor training group only, at both cervical and lumbar levels. These markers included vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and phosphorylated and nonphosphorylated forms of the BDNF receptor tropomyosin-related kinase B (TrkB). In summary, AIH induces plasticity at the cellular level after SCI by altering the expression of major plasticity- and hypoxia-related proteins at spinal regions proximal and remote to the SCI. These changes occur under the same AIH protocol which resulted in recovery of limb function in this animal model. Thus AIH, which induces plasticity in spinal circuitry, could also be an effective therapy to restore motor function after nervous system injury.

Modules in the brain stem and spinal cord underlying motor behaviors

PubMed Central

Cheung, Vincent C. K.; Bizzi, Emilio

2011-01-01

Previous studies using intact and spinalized animals have suggested that coordinated movements can be generated by appropriate combinations of muscle synergies controlled by the central nervous system (CNS). However, which CNS regions are responsible for expressing muscle synergies remains an open question. We address whether the brain stem and spinal cord are involved in expressing muscle synergies used for executing a range of natural movements. We analyzed the electromyographic (EMG) data recorded from frog leg muscles before and after transection at different levels of the neuraxis—rostral midbrain (brain stem preparations), rostral medulla (medullary preparations), and the spinal-medullary junction (spinal preparations). Brain stem frogs could jump, swim, kick, and step, while medullary frogs could perform only a partial repertoire of movements. In spinal frogs, cutaneous reflexes could be elicited. Systematic EMG analysis found two different synergy types: 1) synergies shared between pre- and posttransection states and 2) synergies specific to individual states. Almost all synergies found in natural movements persisted after transection at rostral midbrain or medulla but not at the spinal-medullary junction for swim and step. Some pretransection- and posttransection-specific synergies for a certain behavior appeared as shared synergies for other motor behaviors of the same animal. These results suggest that the medulla and spinal cord are sufficient for the expression of most muscle synergies in frog behaviors. Overall, this study provides further evidence supporting the idea that motor behaviors may be constructed by muscle synergies organized within the brain stem and spinal cord and activated by descending commands from supraspinal areas. PMID:21653716

Clinical, morphologic, and morphometric features of cranial thoracic spinal stenosis in large and giant breed dogs.

PubMed

Johnson, Philippa; De Risio, Luisa; Sparkes, Andrew; McConnell, Fraser; Holloway, Andrew

2012-01-01

The clinical, morphologic, and morphometric features of cranial thoracic spinal stenosis were investigated in large and giant breed dogs. Seventy-nine magnetic resonance imaging studies of the cranial thoracic spine were assessed. Twenty-six were retrieved retrospectively and 53 were acquired prospectively using the same inclusion criteria. Images were evaluated using a modified compression scale as: no osseous stenosis (grade 0), osseous stenosis without spinal cord compression (grade 1), and osseous stenosis with spinal cord compression (grade 2). Morphometric analysis was performed and compared to the subjective grading system. Grades 1 and 2 cranial thoracic spinal stenosis were identified on 24 imaging studies in 23 dogs. Sixteen of 23 dogs had a conformation typified by Molosser breeds and 21/23 were male. The most common sites of stenosis were T2-3 and T3-4. The articular process joints were enlarged with abnormal oblique orientation. Stenosis was dorsolateral, lateralized, or dorsoventral. Concurrent osseous cervical spondylomyelopathy was recognized in six dogs and other neurologic disease in five dogs. Cranial thoracic spinal stenosis was the only finding in 12 dogs. In 9 of these 12 dogs (all grade 2) neurolocalization was to the T3-L3 spinal segment. The median age of these dogs was 9.5 months. In the remaining three dogs neurologic signs were not present. Stenosis ratios were of limited benefit in detecting stenotic sites. Grade 2 cranial thoracic spinal stenosis causing direct spinal cord compression may lead to neurologic signs, however milder stenosis (grade 1) is likely to be subclinical or incidental. © 2012 Veterinary Radiology & Ultrasound.

Descending brain neurons in larval lamprey: Spinal projection patterns and initiation of locomotion

PubMed Central

Shaw, Albert C.; Jackson, Adam W.; Holmes, Tamra; Thurman, Suzie; Davis, G.R.; McClellan, Andrew D.

2010-01-01

In larval lamprey, partial lesions were made in the rostral spinal cord to determine which spinal tracts are important for descending activation of locomotion and to identify descending brain neurons that project in these tracts. In whole animals and in vitro brain/spinal cord preparations, brain-initiated spinal locomotor activity was present when the lateral or intermediate spinal tracts were spared but usually was abolished when the medial tracts were spared. We previously showed that descending brain neurons are located in eleven cell groups, including reticulospinal (RS) neurons in the mesenecephalic reticular nucleus (MRN) as well as the anterior (ARRN), middle (MRRN), and posterior (PRRN) rhombencephalic reticular nuclei. Other descending brain neurons are located in the diencephalic (Di) as well as the anterolateral (ALV), dorsolateral (DLV), and posterolateral (PLV) vagal groups. In the present study, the Mauthner and auxillary Mauthner cells, most neurons in the Di, ALV, DLV, and PLV cell groups, and some neurons in the ARRN and PRRN had crossed descending axons. The majority of neurons projecting in medial spinal tracts included large identified Müller cells and neurons in the Di, MRN, ALV, and DLV. Axons of individual descending brain neurons usually did not switch spinal tracts, have branches in multiple tracts, or cross the midline within the rostral cord. Most neurons that projected in the lateral/intermediate spinal tracts were in the ARRN, MRRN, and PRRN. Thus, output neurons of the locomotor command system are distributed in several reticular nuclei, whose neurons project in relatively wide areas of the cord. PMID:20510243

[The examination of cerebro-spinal fluid in the viroses of the central nervous system (author's transl)].

PubMed

Bonomi, U

1977-01-01

The general outlines for the isolation of viruses from the cerebro-spinal fluid are described. It is suggested to associate to the virus cultivation of the cerebrospinal fluid even the cultivation from other pathological materials as faringeal swabs and stools and the search for antibodies in the blood serum. Researches of viruses in cerebro-spinal fluid done by the Service of Microbiology of the Hospital of Verona have given in 55 cases examined during the year 1976 2 positive isolates; in both mumps virus has been isolated.

Pain intensity and duration can be enhanced by prior challenge: Initial evidence suggestive of a role of microglial priming

PubMed Central

Hains, Leah E.; Loram, Lisa C.; Weiseler, Julie L.; Frank, Matthew G.; Bloss, Erik B.; Sholar, Paige; Taylor, Frederick R; Harrison, Jacqueline A; Martin, Thomas J.; Eisenach, James C.; Maier, Steven F.; Watkins, Linda R.

2010-01-01

Activation of spinal microglia and consequent release of pro-inflammatory mediators facilitate pain. Under certain conditions, responses of activated microglia can become enhanced. Enhanced microglial production of pro-inflammatory products may result from priming (sensitization), similar to macrophage priming. We hypothesized that if spinal microglia were primed by an initial inflammatory challenge, subsequent challenges may create enhanced pain. Here, we used a "two-hit" paradigm using two successive challenges, which affect overlapping populations of spinal microglia, presented two weeks apart. Mechanical allodynia and/or activation of spinal glia were assessed. Initially, laparotomy preceded systemic lipopolysaccharide (LPS). Prior laparotomy caused prolonged microglial (not astrocyte) activation plus enhanced LPS-induced allodynia. In this “two-hit” paradigm, minocycline, a microglial activation inhibitor, significantly reduced later exaggerated pain induced by prior surgery when minocycline was administered intrathecally for 5 days starting either at the time of surgery or 5 days before LPS administration. To test generality of the priming effect, subcutaneous formalin preceded intrathecal HIV-1 gp120, which activates spinal microglia and causes robust allodynia. Prior formalin enhanced intrathecal gp120-induced allodynia, suggesting that microglial priming is not limited to laparotomy and again supporting a spinal site of action. Therefore, spinal microglial priming may increase vulnerability to pain enhancement. PMID:20434956

Is hospital information system relevant to detect surgical site infection? Findings from a prospective surveillance study in posterior instrumented spinal surgery.

PubMed

Boetto, J; Chan-Seng, E; Lonjon, G; Pech, J; Lotthé, A; Lonjon, N

2015-11-01

Spinal instrumentation has a high rate of surgical site infection (SSI), but results greatly vary depending on surveillance methodology, surgical procedures, or quality of follow-up. Our aim was to study true incidence of SSI in spinal surgery by significant data collection, and to compare it with the results obtained through the hospital information system. This work is a single center prospective cohort study that included all patients consecutively operated on for spinal instrumentation by posterior approach over a six-month period regardless the etiology. For all patients, a "high definition" prospective method of surveillance was performed by the infection control (IC) department during at least 12 months after surgery. Results were then compared with findings from automatic surveillance though the hospital information system (HIS). One hundred and fifty-four patients were included. We found no hardly difference between "high definition" and automatic surveillance through the HIS, even if HIS tended to under-estimate the infection rate: rate of surgical site infection was 2.60% and gross SSI incidence rate via the hospital information system was 1.95%. Smoking and alcohol consumption were significantly related to a SSI. Our SSI rates to reflect the true incidence of infectious complications in posterior instrumented adult spinal surgery in our hospital and these results were consistent with the lower levels of published infection rate. In-house surveillance by surgeons only is insufficiently sensitive. Further studies with more patients and a longer inclusion time are needed to conclude if SSI case detection through the HIS could be a relevant and effective alternative method. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Spinal motor control system incorporates an internal model of limb dynamics.

PubMed

Shimansky, Y P

2000-10-01

The existence and utilization of an internal representation of the controlled object is one of the most important features of the functioning of neural motor control systems. This study demonstrates that this property already exists at the level of the spinal motor control system (SMCS), which is capable of generating motor patterns for reflex rhythmic movements, such as locomotion and scratching, without the aid of the peripheral afferent feedback, but substantially modifies the generated activity in response to peripheral afferent stimuli. The SMCS is presented as an optimal control system whose optimality requires that it incorporate an internal model (IM) of the controlled object's dynamics. A novel functional mechanism for the integration of peripheral sensory signals with the corresponding predictive output from the IM, the summation of information precision (SIP) is proposed. In contrast to other models in which the correction of the internal representation of the controlled object's state is based on the calculation of a mismatch between the internal and external information sources, the SIP mechanism merges the information from these sources in order to optimize the precision of the controlled object's state estimate. It is demonstrated, based on scratching in decerebrate cats as an example of the spinal control of goal-directed movements, that the results of computer modeling agree with the experimental observations related to the SMCS's reactions to phasic and tonic peripheral afferent stimuli. It is also shown that the functional requirements imposed by the mathematical model of the SMCS comply with the current knowledge about the related properties of spinal neuronal circuitry. The crucial role of the spinal presynaptic inhibition mechanism in the neuronal implementation of SIP is elucidated. Important differences between the IM and a state predictor employed for compensating for a neural reflex time delay are discussed.

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.

Elimination of Left-Right Reciprocal Coupling in the Adult Lamprey Spinal Cord Abolishes the Generation of Locomotor Activity

PubMed Central

Messina, J. A.; St. Paul, Alison; Hargis, Sarah; Thompson, Wengora E.; McClellan, Andrew D.

2017-01-01

The contribution of left-right reciprocal coupling between spinal locomotor networks to the generation of locomotor activity was tested in adult lampreys. Muscle recordings were made from normal animals as well as from experimental animals with rostral midline (ML) spinal lesions (~13%→35% body length, BL), before and after spinal transections (T) at 35% BL. Importantly, in the present study actual locomotor movements and muscle burst activity, as well as other motor activity, were initiated in whole animals by descending brain-spinal pathways in response to sensory stimulation of the anterior head. For experimental animals with ML spinal lesions, sensory stimulation could elicit well-coordinated locomotor muscle burst activity, but with some significant differences in the parameters of locomotor activity compared to those for normal animals. Computer models representing normal animals or experimental animals with ML spinal lesions could mimic many of the differences in locomotor activity. For experimental animals with ML and T spinal lesions, right and left rostral hemi-spinal cords, disconnected from intact caudal cord, usually produced tonic or unpatterned muscle activity. Hemi-spinal cords sometimes generated spontaneous or sensory-evoked relatively high frequency “burstlet” activity that probably is analogous to the previously described in vitro “fast rhythm”, which is thought to represent lamprey locomotor activity. However, “burstlet” activity in the present study had parameters and features that were very different than those for lamprey locomotor activity: average frequencies were ~25 Hz, but individual frequencies could be >50 Hz; burst proportions (BPs) often varied with cycled time; “burstlet” activity usually was not accompanied by a rostrocaudal phase lag; and following ML spinal lesions alone, “burstlet” activity could occur in the presence or absence of swimming burst activity, suggesting the two were generated by different mechanisms. In summary, for adult lampreys, left and right hemi-spinal cords did not generate rhythmic locomotor activity in response to descending inputs from the brain, suggesting that left-right reciprocal coupling of spinal locomotor networks contributes to both phase control and rhythmogenesis. In addition, the present study indicates that extreme caution should be exercised when testing the operation of spinal locomotor networks using artificial activation of isolated or reduced nervous system preparations. PMID:29225569

Soft-coupling suspension system for an intradural spinal cord stimulator: Biophysical performance characteristics

NASA Astrophysics Data System (ADS)

Oya, H.; Safayi, S.; Jeffery, N. D.; Viljoen, S.; Reddy, C. G.; Dalm, B. D.; Kanwal, J. K.; Gillies, G. T.; Howard, M. A.

2013-10-01

We have characterized the mechanical compliance of an improved version of the suspension system used to position the electrode-bearing membrane of an intradural neuromodulator on the dorsal pial surface of the spinal cord. Over the compression span of 5 mm, it exhibited a restoring force of 2.4 μN μm-1 and a mean pressure of 0.5 mm Hg (=66 Pa) on the surface below it, well within the range of normal intrathecal pressures. We have implanted prototype devices employing this suspension and a novel device fixation technique in a chronic ovine model of spinal cord stimulation and found that it maintains stable contact at the electrode-pia interface without lead fracture, as determined by measurement of the inter-contact impedances.

Fully implantable, battery-free wireless optoelectronic devices for spinal optogenetics.

PubMed

Samineni, Vijay K; Yoon, Jangyeol; Crawford, Kaitlyn E; Jeong, Yu Ra; McKenzie, Kajanna C; Shin, Gunchul; Xie, Zhaoqian; Sundaram, Saranya S; Li, Yuhang; Yang, Min Young; Kim, Jeonghyun; Wu, Di; Xue, Yeguang; Feng, Xue; Huang, Yonggang; Mickle, Aaron D; Banks, Anthony; Ha, Jeong Sook; Golden, Judith P; Rogers, John A; Gereau, Robert W

2017-11-01

The advent of optogenetic tools has allowed unprecedented insights into the organization of neuronal networks. Although recently developed technologies have enabled implementation of optogenetics for studies of brain function in freely moving, untethered animals, wireless powering and device durability pose challenges in studies of spinal cord circuits where dynamic, multidimensional motions against hard and soft surrounding tissues can lead to device degradation. We demonstrate here a fully implantable optoelectronic device powered by near-field wireless communication technology, with a thin and flexible open architecture that provides excellent mechanical durability, robust sealing against biofluid penetration and fidelity in wireless activation, thereby allowing for long-term optical stimulation of the spinal cord without constraint on the natural behaviors of the animals. The system consists of a double-layer, rectangular-shaped magnetic coil antenna connected to a microscale inorganic light-emitting diode (μ-ILED) on a thin, flexible probe that can be implanted just above the dura of the mouse spinal cord for effective stimulation of light-sensitive proteins expressed in neurons in the dorsal horn. Wireless optogenetic activation of TRPV1-ChR2 afferents with spinal μ-ILEDs causes nocifensive behaviors and robust real-time place aversion with sustained operation in animals over periods of several weeks to months. The relatively low-cost electronics required for control of the systems, together with the biocompatibility and robust operation of these devices will allow broad application of optogenetics in future studies of spinal circuits, as well as various peripheral targets, in awake, freely moving and untethered animals, where existing approaches have limited utility.

Lentiviral-mediated Targeted NF-κB Blockade in Dorsal Spinal Cord Glia Attenuates Sciatic Nerve Injury-induced Neuropathic Pain in the Rat.

PubMed

Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

2007-04-01

Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor κB (NF-κB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-κB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-κB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-κB super- repressor IκBα resulted in an inhibition of the NF-κB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IκBα overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-κB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-κB pathway in the development of neuropathic pain after peripheral nerve injury. Copyright © 2007 The American Society of Gene Therapy. Published by Elsevier Inc. All rights reserved.

Analysis of the fibroblast growth factor system reveals alterations in a mouse model of spinal muscular atrophy.

PubMed

Hensel, Niko; Ratzka, Andreas; Brinkmann, Hella; Klimaschewski, Lars; Grothe, Claudia; Claus, Peter

2012-01-01

The monogenetic disease Spinal Muscular Atrophy (SMA) is characterized by a progressive loss of motoneurons leading to muscle weakness and atrophy due to severe reduction of the Survival of Motoneuron (SMN) protein. Several models of SMA show deficits in neurite outgrowth and maintenance of neuromuscular junction (NMJ) structure. Survival of motoneurons, axonal outgrowth and formation of NMJ is controlled by neurotrophic factors such as the Fibroblast Growth Factor (FGF) system. Besides their classical role as extracellular ligands, some FGFs exert also intracellular functions controlling neuronal differentiation. We have previously shown that intracellular FGF-2 binds to SMN and regulates the number of a subtype of nuclear bodies which are reduced in SMA patients. In the light of these findings, we systematically analyzed the FGF-system comprising five canonical receptors and 22 ligands in a severe mouse model of SMA. In this study, we demonstrate widespread alterations of the FGF-system in both muscle and spinal cord. Importantly, FGF-receptor 1 is upregulated in spinal cord at a pre-symptomatic stage as well as in a mouse motoneuron-like cell-line NSC34 based model of SMA. Consistent with that, phosphorylations of FGFR-downstream targets Akt and ERK are increased. Moreover, ERK hyper-phosphorylation is functionally linked to FGFR-1 as revealed by receptor inhibition experiments. Our study shows that the FGF system is dysregulated at an early stage in SMA and may contribute to the SMA pathogenesis.

Activity-Based Restorative Therapies: Concepts and Applications in Spinal Cord Injury-Related Neurorehabilitation

ERIC Educational Resources Information Center

Sadowsky, Cristina L.; McDonald, John W.

2009-01-01

Physical rehabilitation following spinal cord injury-related paralysis has traditionally focused on teaching compensatory techniques, thus enabling the individual to achieve day-to-day function despite significant neurological deficits. But the concept of an irreparable central nervous system (CNS) is slowly being replaced with evidence related to…

77 FR 22632 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-16

...--Repository (SCIDO-R)-VA'' (108VA11S) as set forth in the Federal Register 74 FR 11185-11186 dated March 16.... SUPPLEMENTARY INFORMATION: The Spinal Cord Injury and Disorders Outcomes--Repository (SCIDO-R) provides a registry of veterans with spinal cord injury and disorders (SCI&D). This repository contains pertinent...

Innovations in interventional pain management of chronic spinal pain.

PubMed

Manchikanti, Laxmaiah; Boswell, Mark V; Hirsch, Joshua A

2016-09-01

Interventional pain management dates back to 1901, with significant innovations, which include the definition, literature synthesis, pathophysiology, and technical interventions. Interventional pain management and interventional techniques include neural blockade, neural ablative procedures, spinal cord and peripheral nerve stimulation, intrathecal drug delivery systems, minimally invasive lumbar decompression (MILD®), percutaneous endoscopic spinal decompression, and regenerative medicine. In addition, advances are also related to the evidence synthesis of comparative effectiveness research. Expert commentary: Multiple innovations in interventional pain management and potential innovations may reduce costs and improve care and outcomes with proper evidence synthesis and application of principles of evidence-based medicine. Innovations in interventional pain management in managing chronic spinal pain depend on extensive research and appropriate evidence synthesis. Innovations should be developed in conjunction with health care policy based on principles of evidence-based medicine.

[Reha-Stepper locomotion therapy in early rehabilitation of paraplegic patients].

PubMed

Rupp, R; Eberhard, S; Schreier, R; Colombo, G

2002-01-01

Treadmill training with partial body weight support was shown to significantly improve the constitution and gait capacity of incomplete spinal cord injured (SCI) persons. The main requirement for application of this therapy is a sufficient capacity of the cardiovascular system. Most of the SCI patients do not comply with this requirement in the first few weeks after spinal cord injury, where spinal reflexes are frequently missing (spinal shock). To offer SCI patients a locomotion therapy at this early stage of rehabilitation we developed a novel, active tilt-table, the Reha-Stepper, that moves the lower limbs in an almost physiological manner in terms of kinematic and kinetic parameters. The tilt of the device can be continuously increased from horizontal to almost upright position adapted to the status of the patient.

Braided tubular superelastic cables provide improved spinal stability compared to multifilament sublaminar cables.

PubMed

Tremblay, Jaëlle; Mac-Thiong, Jean-Marc; Brailovski, Vladimir; Petit, Yvan

2015-09-01

This study investigates the use of braided tubular superelastic cables, previously used for sternum closure following sternotomy, as sublaminar fixation method. It compares the biomechanical performance of spinal instrumentation fixation systems with regular sublaminar cables and proprietary superelastic cables. A hybrid experimental protocol was applied to six porcine L1-L4 spinal segments to compare multifilament sublaminar cables (Atlas, Medtronic Sofamor Danek, Memphis, TN) with proprietary superelastic cables. First, intact total range of motion was determined for all specimens using pure moment loading. Second, pure moments were imposed to the instrumented specimens until these intact total ranges of motion were reproduced. Compared to the intact specimens, the use of superelastic cables resulted in stiffer instrumented specimens than the use of multifilament cables for all the loading modes except axial torsion. Consequently, the superelastic cables limited the instrumented segments mobility more than the multifilament cables. Spinal instrumentation fixation systems using superelastic cables could be a good alternative to conventional sublaminar cables as it maintains a constant stabilization of the spine during loading. © IMechE 2015.

Squalenoyl adenosine nanoparticles provide neuroprotection after stroke and spinal cord injury

NASA Astrophysics Data System (ADS)

Gaudin, Alice; Yemisci, Müge; Eroglu, Hakan; Lepetre-Mouelhi, Sinda; Turkoglu, Omer Faruk; Dönmez-Demir, Buket; Caban, Seçil; Sargon, Mustafa Fevzi; Garcia-Argote, Sébastien; Pieters, Grégory; Loreau, Olivier; Rousseau, Bernard; Tagit, Oya; Hildebrandt, Niko; Le Dantec, Yannick; Mougin, Julie; Valetti, Sabrina; Chacun, Hélène; Nicolas, Valérie; Desmaële, Didier; Andrieux, Karine; Capan, Yilmaz; Dalkara, Turgay; Couvreur, Patrick

2014-12-01

There is an urgent need to develop new therapeutic approaches for the treatment of severe neurological trauma, such as stroke and spinal cord injuries. However, many drugs with potential neuropharmacological activity, such as adenosine, are inefficient upon systemic administration because of their fast metabolization and rapid clearance from the bloodstream. Here, we show that conjugation of adenosine to the lipid squalene and the subsequent formation of nanoassemblies allows prolonged circulation of this nucleoside, providing neuroprotection in mouse stroke and rat spinal cord injury models. The animals receiving systemic administration of squalenoyl adenosine nanoassemblies showed a significant improvement of their neurologic deficit score in the case of cerebral ischaemia, and an early motor recovery of the hindlimbs in the case of spinal cord injury. Moreover, in vitro and in vivo studies demonstrated that the nanoassemblies were able to extend adenosine circulation and its interaction with the neurovascular unit. This Article shows, for the first time, that a hydrophilic and rapidly metabolized molecule such as adenosine may become pharmacologically efficient owing to a single conjugation with the lipid squalene.

VGLUTs in Peripheral Neurons and the Spinal Cord: Time for a Review

PubMed Central

Brumovsky, Pablo R.

2013-01-01

Vesicular glutamate transporters (VGLUTs) are key molecules for the incorporation of glutamate in synaptic vesicles across the nervous system, and since their discovery in the early 1990s, research on these transporters has been intense and productive. This review will focus on several aspects of VGLUTs research on neurons in the periphery and the spinal cord. Firstly, it will begin with a historical account on the evolution of the morphological analysis of glutamatergic systems and the pivotal role played by the discovery of VGLUTs. Secondly, and in order to provide an appropriate framework, there will be a synthetic description of the neuroanatomy and neurochemistry of peripheral neurons and the spinal cord. This will be followed by a succinct description of the current knowledge on the expression of VGLUTs in peripheral sensory and autonomic neurons and neurons in the spinal cord. Finally, this review will address the modulation of VGLUTs expression after nerve and tissue insult, their physiological relevance in relation to sensation, pain, and neuroprotection, and their potential pharmacological usefulness. PMID:24349795

Comparison of alpha-synuclein immunoreactivity in the spinal cord between the adult and aged beagle dog

PubMed Central

Ahn, Ji-Hyeon; Choi, Jung-Hoon; Park, Joon-Ha; Yan, Bing-Chun; Kim, In-Hye; Lee, Jae-Chul; Lee, Dae-Hwan; Kim, Jin-Sang

2012-01-01

Alpha-synuclein (α-syn) is a presynaptic protein that is richly expressed in the central and peripheral nervous systems of mammals, and it is related to the pathogenesis of Parkinson's disease and other neurodegenerative disorders. In the present study, we compared the distribution of the immunoreactivity of α-syn and its related gliosis in the spinal cord of young adult (2-3 years) and aged (10-12 years) beagle dogs. We discovered that α-syn immunoreactivity was present in many neurons in the thoracic level of the aged spinal cord, however, its protein level was not distinct inform that of the adult spinal cord. In addition, ionized calcium-binding adapter molecule-1 (a marker for microglia) immunoreactivity, and not glial fibrillary acidic protein (a marker for astrocytes) immunoreactivity, was somewhat increased in the aged group compared to the adult group. These results indicate that α-syn immunoreactivity was not dramatically changed in the dog spinal cord during aging. PMID:23091516

The genetic basis of intradural spinal tumors and its impact on clinical treatment.

PubMed

Karsy, Michael; Guan, Jian; Sivakumar, Walavan; Neil, Jayson A; Schmidt, Meic H; Mahan, Mark A

2015-08-01

Genetic alterations in the cells of intradural spinal tumors can have a significant impact on the treatment options, counseling, and prognosis for patients. Although surgery is the primary therapy for most intradural tumors, radiochemothera-peutic modalities and targeted interventions play an ever-evolving role in treating aggressive cancers and in addressing cancer recurrence in long-term survivors. Recent studies have helped delineate specific genetic and molecular differences between intradural spinal tumors and their intracranial counterparts and have also identified significant variation in therapeutic effects on these tumors. This review discusses the genetic and molecular alterations in the most common intradural spinal tumors in both adult and pediatrie patients, including nerve sheath tumors (that is, neurofibroma and schwannoma), meningioma, ependymoma, astrocytoma (that is, low-grade glioma, anaplastic astrocytoma, and glioblastoma), hemangioblastoma, and medulloblastoma. It also examines the genetics of metastatic tumors to the spinal cord, arising either from the CNS or from systemic sources. Importantly, the impact of this knowledge on therapeutic options and its application to clinical practice are discussed.

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

PubMed Central

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

2016-01-01

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

Mechanical hypersensitivity, sympathetic sprouting, and glial activation are attenuated by local injection of corticosteroid near the lumbar ganglion in a rat model of neuropathic pain.

PubMed

Li, Jing-Yi; Xie, Wenrui; Strong, Judith A; Guo, Qu-Lian; Zhang, Jun-Ming

2011-01-01

Inflammatory responses in the lumbar dorsal root ganglion (DRG) play a key role in pathologic pain states. Systemic administration of a common anti-inflammatory corticosteroid, triamcinolone acetonide (TA), reduces sympathetic sprouting, mechanical pain behavior, spontaneous bursting activity, and cytokine and nerve growth factor production in the DRG. We hypothesized that systemic TA effects are primarily due to local effects on the DRG. Male Sprague-Dawley rats were divided into 4 groups: SNL (tight ligation and transection of spinal nerves) and normal with and without a single dose of TA injectable suspension slowly injected onto the surface of DRG and surrounding region at the time of SNL or sham surgery. Mechanical threshold was tested on postoperative days 1, 3, 5, and 7. Immunohistochemical staining examined tyrosine hydroxylase and glial fibrillary acidic protein in DRG and CD11B antibody (OX-42) in spinal cord. Local TA treatment attenuated mechanical sensitivity, reduced sympathetic sprouting in the DRG, and decreased satellite glia activation in the DRG and microglia activation in the spinal cord after SNL. A single injection of corticosteroid in the vicinity of the axotomized DRG can mimic many effects of systemic TA, mitigating behavioral and cellular abnormalities induced by spinal nerve ligation. This provides a further rationale for the use of localized steroid injections clinically and provides further support for the idea that localized inflammation at the level of the DRG is an important component of the spinal nerve ligation model, commonly classified as neuropathic pain model.

A multimedia Electronic Patient Record (ePR) system for Image-Assisted Minimally Invasive Spinal Surgery

PubMed Central

Documet, Jorge; Le, Anh; Liu, Brent; Chiu, John; Huang, HK

2009-01-01

Purpose This paper presents the concept of bridging the gap between diagnostic images and image-assisted surgical treatment through the development of a one-stop multimedia electronic patient record (ePR) system that manages and distributes the real-time multimodality imaging and informatics data that assists the surgeon during all clinical phases of the operation from planning Intra-Op to post-care follow-up. We present the concept of this multimedia ePR for surgery by first focusing on Image-Assisted Minimally Invasive Spinal Surgery as a clinical application. Methods Three clinical Phases of Minimally Invasive Spinal Surgery workflow in Pre-Op, Intra-Op, and Post Op are discussed. The ePR architecture was developed based on the three-phased workflow, which includes the Pre-Op, Intra-Op, and Post-Op modules and four components comprising of the input integration unit, fault-tolerant gateway server, fault-tolerant ePR server, and the visualization and display. A prototype was built and deployed to a Minimally Invasive Spinal Surgery clinical site with user training and support for daily use. Summary A step-by step approach was introduced to develop a multi-media ePR system for Imaging-Assisted Minimally Invasive Spinal Surgery that includes images, clinical forms, waveforms, and textual data for planning the surgery, two real-time imaging techniques (digital fluoroscopic, DF) and endoscope video images (Endo), and more than half a dozen live vital signs of the patient during surgery. Clinical implementation experiences and challenges were also discussed. PMID:20033507

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.

Excess cost and inpatient stay of treating deep spinal surgical site infections.

PubMed

Barnacle, James; Wilson, Dianne; Little, Christopher; Hoffman, Christopher; Raymond, Nigel

2018-05-18

To determine the excess cost and hospitalisation associated with surgical site infections (SSI) following spinal operations in a New Zealand setting. We identified inpatients treated for deep SSI following primary or revision spinal surgery at a regional tertiary spinal centre between 2009 and 2016. Excess cost and excess length of stay (LOS) were calculated via a clinical costing system using procedure-matched controls. Twenty-eight patients were identified. Twenty-five had metalware following spinal fusion surgery, while three had non-instrumented decompression and/or discectomy. Five were diagnosed during their index hospitalisation and 23 (82%) were re-admitted. The average excess SSI cost was NZ$51,434 (range $1,398-$262,206.16) and LOS 37.1 days (range 7-275 days). Infections following metalware procedures had a greater excess cost (average $56,258.90 vs. $11,228.61) and LOS (average 40.4 days vs. 9.7 days) than procedures without metalware. The costs associated with spinal SSI are significant and comparable to a previous New Zealand study of hip and knee prosthesis SSI. More awareness of the high costs involved should encourage research and implementation of infection prevention strategies.

Spontaneous motor rhythms of the back and legs in a patient with a complete spinal cord transection.

PubMed

Nadeau, Sylvie; Jacquemin, Géraldine; Fournier, Christine; Lamarre, Yves; Rossignol, Serge

2010-05-01

Spontaneous activity originating from the spinal cord has been sporadically reported in humans. Investigation of such rhythmic activity of the trunk and legs in a 49-year-old male patient who had a complete severance of the spinal cord at the fifth thoracic vertebra. A multichannel electromyography (EMG) study was performed together with kinematics measurements obtained from an Optotrak system. Episodes of rhythmic trunk and lower limb movements started 6 to 7 years after the spinal lesion, recurred at 2 to 3 month intervals, and continued uninterrupted for 2 to 3 days despite continuous delivery of intrathecal baclofen. Several muscles discharged more or less synchronously on both sides but others clearly alternated, for instance, between hip flexors and knee or ankle extensors. Sensory stimuli (hip repositioning or skin pinch) altered significantly the baseline rhythm of about 1 Hz. The patient had both hips injected with corticosteroids and was free of these episodic rhythmic crises for more than 6 months. The rhythmic activity observed in the patient appeared related to the activation of a spinal pattern generator akin to what has been described in most animal species after complete spinal lesions.

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.

The Impact of Metastatic Spinal Tumor Location on 30-Day Perioperative Mortality and Morbidity After Surgical Decompression.

PubMed

Hussain, Awais K; Vig, Khushdeep S; Cheung, Zoe B; Phan, Kevin; Lima, Mauricio C; Kim, Jun S; Kaji, Deepak A; Arvind, Varun; Cho, Samuel Kang-Wook

2018-06-01

A retrospective cohort study from 2011 to 2014 was performed using the American College of Surgeons National Surgical Quality Improvement Program database. The purpose of this study was to assess the impact of tumor location in the cervical, thoracic, or lumbosacral spine on 30-day perioperative mortality and morbidity after surgical decompression of metastatic extradural spinal tumors. Operative treatment of metastatic spinal tumors involves extensive procedures that are associated with significant complication rates and healthcare costs. Past studies have examined various risk factors for poor clinical outcomes after surgical decompression procedures for spinal tumors, but few studies have specifically investigated the impact of tumor location on perioperative mortality and morbidity. We identified 2238 patients in the American College of Surgeons National Surgical Quality Improvement Program database who underwent laminectomy for excision of metastatic extradural tumors in the cervical, thoracic, or lumbosacral spine. Baseline patient characteristics were collected from the database. Univariate and multivariate regression analyses were performed to examine the association between spinal tumor location and 30-day perioperative mortality and morbidity. On univariate analysis, cervical spinal tumors were associated with the highest rate of pulmonary complications. Multivariate regression analysis demonstrated that cervical spinal tumors had the highest odds of multiple perioperative complications. However, thoracic spinal tumors were associated with the highest risk of intra- or postoperative blood transfusion. In contrast, patients with metastatic tumors in the lumbosacral spine had lower odds of perioperative mortality, pulmonary complications, and sepsis. Tumor location is an independent risk factor for perioperative mortality and morbidity after surgical decompression of metastatic spinal tumors. The addition of tumor location to existing prognostic scoring systems may help to improve their predictive accuracy. 3.

Intraoperative electroacupuncture relieves remifentanil-induced postoperative hyperalgesia via inhibiting spinal glial activation in rats.

PubMed

Shi, Changxi; Liu, Yue; Zhang, Wei; Lei, Yishan; Lu, Cui'e; Sun, Rao; Sun, Yu'e; Jiang, Ming; Gu, Xiaoping; Ma, Zhengliang

2017-01-01

Background Accumulating studies have suggested that remifentanil, the widely-used opioid analgesic in clinical anesthesia, can activate the pronociceptive systems and enhance postoperative pain. Glial cells are thought to be implicated in remifentanil-induced hyperalgesia. Electroacupuncture is a complementary therapy to relieve various pain conditions with few side effects, and glial cells may be involved in its antinociceptive effect. In this study, we investigated whether intraoperative electroacupuncture could relieve remifentanil-induced postoperative hyperalgesia by inhibiting the activation of spinal glial cells, the production of spinal proinflammatory cytokines, and the activation of spinal mitogen-activated protein kinases. Methods A rat model of remifentanil-induced postoperative hyperalgesia was used in this study. Electroacupuncture during surgery was conducted at bilateral Zusanli (ST36) acupoints. Behavior tests, including mechanical allodynia and thermal hyperalgesia, were performed at different time points. Astrocytic marker glial fibrillary acidic protein, microglial marker Iba1, proinflammatory cytokines, and phosphorylated mitogen-activated protein kinases in the spinal cord were detected by Western blot and/or immunofluorescence. Results Mechanical allodynia and thermal hyperalgesia were induced by both surgical incision and remifentanil infusion, and remifentanil infusion significantly exaggerated and prolonged incision-induced pronociceptive effects. Glial fibrillary acidic protein, Iba1, proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α), and phosphorylated mitogen-activated protein kinases (p-p38, p-JNK, and p-ERK1/2) were upregulated after surgical incision, remifentanil infusion, and especially after their combination. Intraoperative electroacupuncture significantly attenuated incision- and/or remifentanil-induced pronociceptive effects, spinal glial activation, proinflammatory cytokine upregulation, and phosphorylated mitogen-activated protein kinase upregulation. Conclusions Our study suggests that remifentanil-induced postoperative hyperalgesia can be relieved by intraoperative electroacupuncture via inhibiting the activation of spinal glial cells, the upregulation of spinal proinflammatory cytokines, and the activation of spinal mitogen-activated protein kinases.

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

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.

The distribution of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the medulla oblongata, spinal cord, cranial and spinal nerves of frog, Microhyla ornata.

PubMed

Jadhao, Arun G; Biswas, Saikat P; Bhoyar, Rahul C; Pinelli, Claudia

2017-04-01

Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) enzymatic activity has been reported in few amphibian species. In this study, we report its unusual localization in the medulla oblongata, spinal cord, cranial nerves, spinal nerves, and ganglions of the frog, Microhyla ornata. In the rhombencephalon, at the level of facial and vagus nerves, the NADPH-d labeling was noted in the nucleus of the abducent and facial nerves, dorsal nucleus of the vestibulocochlear nerve, the nucleus of hypoglossus nerve, dorsal and lateral column nucleus, the nucleus of the solitary tract, the dorsal field of spinal grey, the lateral and medial motor fields of spinal grey and radix ventralis and dorsalis (2-10). Many ependymal cells around the lining of the fourth ventricle, both facial and vagus nerves and dorsal root ganglion, were intensely labeled with NADPH-d. Most strikingly the NADPH-d activity was seen in small and large sized motoneurons in both medial and lateral motor neuron columns on the right and left sides of the brain. This is the largest stained group observed from the caudal rhombencephalon up to the level of radix dorsalis 10 in the spinal cord. The neurons were either oval or elongated in shape with long processes and showed significant variation in the nuclear and cellular diameter. A massive NADPH-d activity in the medulla oblongata, spinal cord, and spinal nerves implied an important role of this enzyme in the neuronal signaling as well as in the modulation of motor functions in the peripheral nervous systems of the amphibians. Copyright © 2017 Elsevier B.V. All rights reserved.

Superficial NK1 expressing spinal dorsal horn neurones modulate inhibitory neurotransmission mediated by spinal GABA(A) receptors.

PubMed

Rahman, Wahida; Sikandar, Shafaq; Sikander, Shafaq; Suzuki, Rie; Hunt, Stephen P; Dickenson, Anthony H

2007-06-04

Lamina 1 projection neurones which express the NK1 receptor (NK1R+) drive a descending serotonergic pathway from the brainstem that enhances spinal dorsal horn neuronal activity via the facilitatory spinal 5-HT3 receptor. Selective destruction of these cells via lumbar injection of substance P-saporin (SP-SAP) attenuates pain behaviours, including mechanical and thermal hypersensitivity, which are mirrored by deficits in the evoked responses of lamina V-VI wide dynamic range (WDR) neurones to noxious stimuli. To assess whether removing the origin of this facilitatory spino-bulbo-spinal loop results in alterations in GABAergic spinal inhibitory systems, the effects of spinal bicuculline, a selective GABA(A) receptor antagonist, on the evoked neuronal responses to electrical (Abeta-, Adelta-, C-fibre, post-discharge and Input) and mechanical (brush, prod and von Frey (vF) 8 and 26 g) stimuli were measured in SAP and SP-SAP groups. In the SAP control group, bicuculline produced a significant dose related facilitation of the electrically evoked Adelta-, C-fibre, post-discharge and input neuronal responses. The evoked mechanical (prod, vF8 g and 26 g) responses were also significantly increased. Brush evoked neuronal responses in these animals were enhanced but did not reach significance. This facilitatory effect of bicuculline, however, was lost in the SP-SAP treated group. The generation of intrinsic GABAergic transmission in the spinal cord appears dependent on NK1 bearing neurons, yet despite the loss of GABAergic inhibitory controls after SP-SAP treatment, the net effect is a decrease in spinal cord excitability. Thus activation of these cells predominantly drives facilitation.

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.

Definition and management of varicella zoster virus-associated meningoradiculitis: a case report.

PubMed

Luisier, Vincent; Weber, Lalensia; Fishman, Daniel; Praz, Gérard; Ghika, Joseph-André; Genoud, Didier; Chabwine, Joelle Nsimire

2016-09-26

The varicella zoster virus affects the central or peripheral nervous systems upon reactivation, especially when cell-mediated immunity is impaired. Among varicella zoster virus-related neurological syndromes, meningoradiculitis is an ill-defined condition for which clear management guidelines are still lacking. Zoster paresis is usually considered to be a varicella zoster virus-peripheral nervous system complication and treated with oral antiviral therapy. Yet in the literature, the few reported cases of herpes zoster with mild cerebral spinal fluid inflammation were all considered meningoradiculitis and treated using intravenous antiviral drugs, despite absence of systemic signs of meningitis. Nevertheless, these two clinical pictures are very similar. We report the case of an alcohol-dependent elderly Caucasian man presenting with left lower limb zoster paresis and mild cerebral spinal fluid inflammation, with favorable outcome upon IV antiviral treatment. We discuss interpretation of liquor inflammation in the absence of clinical meningitis and implications for the antiviral treatment route. From this case report we suggest that varicella zoster virus-associated meningoradiculitis should necessarily include meningitis symptoms with the peripheral neurological deficits and cerebral spinal fluid inflammation, requiring intravenous antiviral treatment. In the absence of (cell-mediated) immunosuppression, isolated zoster paresis does not necessitate spinal tap or intravenous antiviral therapy.

The human natural killer-1 (HNK-1) glycan mimetic ursolic acid promotes functional recovery after spinal cord injury in mouse.

PubMed

Sahu, Sudhanshu; Li, Rong; Kadeyala, Praveen Kumar; Liu, Shisong; Schachner, Melitta

2018-05-01

Human natural killer-1 (HNK-1) cell antigen is a glycan epitope involved in several neural events, such as neuritogenesis, myelination, synaptic plasticity and regeneration of the nervous system after injury. We have recently identified the small organic compound ursolic acid (UA) as a HNK-1 mimetic with the aim to test its therapeutic potential in the central nervous system. UA, a plant-derived pentacyclic triterpenoid, is well known for its multiple biological functions, including neuroprotective, antioxidant and anti-inflammatory activities. In the present study, we evaluated its functions in a mouse model of spinal cord injury (SCI) and explored the molecular mechanisms underlying its positive effects. Oral administration of UA to mice 1 h after SCI and thereafter once daily for 6 weeks enhanced the regaining of motor functions and axonal regrowth, and decreased astrogliosis. UA administration decreased levels of proinflammatory markers, including interleukin-6 and tumor necrosis factor-α, in the injured spinal cord at the acute phase of inflammation and activated the mitogen-activated protein kinase and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways in the injured spinal cord. Taken together, these results suggest that UA may be a candidate for treatment of nervous system injuries. Copyright © 2017. Published by Elsevier Inc.

Dopamine: a parallel pathway for the modulation of spinal locomotor networks

PubMed Central

Sharples, Simon A.; Koblinger, Kathrin; Humphreys, Jennifer M.; Whelan, Patrick J.

2014-01-01

The spinal cord contains networks of neurons that can produce locomotor patterns. To readily respond to environmental conditions, these networks must be flexible yet at the same time robust. Neuromodulators play a key role in contributing to network flexibility in a variety of invertebrate and vertebrate networks. For example, neuromodulators contribute to altering intrinsic properties and synaptic weights that, in extreme cases, can lead to neurons switching between networks. Here we focus on the role of dopamine in the control of stepping networks in the spinal cord. We first review the role of dopamine in modulating rhythmic activity in the stomatogastric ganglion (STG) and the leech, since work from these preparations provides a foundation to understand its role in vertebrate systems. We then move to a discussion of dopamine’s role in modulation of swimming in aquatic species such as the larval xenopus, lamprey and zebrafish. The control of terrestrial walking in vertebrates by dopamine is less studied and we review current evidence in mammals with a focus on rodent species. We discuss data suggesting that the source of dopamine within the spinal cord is mainly from the A11 area of the diencephalon, and then turn to a discussion of dopamine’s role in modulating walking patterns from both in vivo and in vitro preparations. Similar to the descending serotonergic system, the dopaminergic system may serve as a potential target to promote recovery of locomotor function following spinal cord injury (SCI); evidence suggests that dopaminergic agonists can promote recovery of function following SCI. We discuss pharmacogenetic and optogenetic approaches that could be deployed in SCI and their potential tractability. Throughout the review we draw parallels with both noradrenergic and serotonergic modulatory effects on spinal cord networks. In all likelihood, a complementary monoaminergic enhancement strategy should be deployed following SCI. PMID:24982614

Nogo-receptor gene activity: cellular localization and developmental regulation of mRNA in mice and humans.

PubMed

Josephson, Anna; Trifunovski, Alexandra; Widmer, Hans Ruedi; Widenfalk, Johan; Olson, Lars; Spenger, Christian

2002-11-18

Nogo (reticulon-4) is a myelin-associated protein that is expressed in three different splice variants, Nogo-A, Nogo-B, and Nogo-C. Nogo-A inhibits neurite regeneration in the central nervous system. Messenger RNA encoding Nogo is expressed in oligodendrocytes and central and peripheral neurons, but not in astrocytes or Schwann cells. Nogo is a transmembraneous protein; the extracellular domain is termed Nogo-66, and a Nogo-66-receptor (Nogo-R) has been identified. We performed in situ hybridization in human and mouse nervous tissues to map the cellular distribution of Nogo-R gene activity patterns in fetal and adult human spinal cord and sensory ganglia, adult human brain, and the nervous systems of developing and adult mice. In the human fetus Nogo-R was transcribed in the ventral horn of the spinal cord and in dorsal root ganglia. In adult human tissues Nogo-R gene activity was found in neocortex, hippocampus, amygdala, and a subset of large and medium-sized neurons of the dorsal root ganglia. Nogo-R mRNA was not expressed in the adult human spinal cord at detectable levels. In the fetal mouse, Nogo-R was diffusely expressed in brain, brainstem, trigeminal ganglion, spinal cord, and dorsal root ganglia at all stages. In the adult mouse strong Nogo-R mRNA expression was found in neurons in neocortex, hippocampus, amygdala, habenula, thalamic nuclei, brainstem, the granular cell layer of cerebellum, and the mitral cell layer of the olfactory bulb. Neurons in the adult mouse striatum, the medial septal nucleus, and spinal cord did not express Nogo-R mRNA at detectable levels. In summary, Nogo-66-R mRNA expression in humans and mice was observed in neurons of the developing nervous system Expression was downregulated in the adult spinal cord of both species, and specific expression patterns were seen in the adult brain. Copyright 2002 Wiley-Liss, Inc.

Predictive value of seven preoperative prognostic scoring systems for spinal metastases.

PubMed

Leithner, Andreas; Radl, Roman; Gruber, Gerald; Hochegger, Markus; Leithner, Katharina; Welkerling, Heike; Rehak, Peter; Windhager, Reinhard

2008-11-01

Predicting prognosis is the key factor in selecting the proper treatment modality for patients with spinal metastases. Therefore, various assessment systems have been designed in order to provide a basis for deciding the course of treatment. Such systems have been proposed by Tokuhashi, Sioutos, Tomita, Van der Linden, and Bauer. The scores differ greatly in the kind of parameters assessed. The aim of this study was to evaluate the prognostic value of each score. Eight parameters were assessed for 69 patients (37 male, 32 female): location, general condition, number of extraspinal bone metastases, number of spinal metastases, visceral metastases, primary tumour, severity of spinal cord palsy, and pathological fracture. Scores according to Tokuhashi (original and revised), Sioutos, Tomita, Van der Linden, and Bauer were assessed as well as a modified Bauer score without scoring for pathologic fracture. Nineteen patients were still alive as of September 2006 with a minimum follow-up of 12 months. All other patients died after a mean period of 17 months after operation. The mean overall survival period was only 3 months for lung cancer, followed by prostate (7 months), kidney (23 months), breast (35 months), and multiple myeloma (51 months). At univariate survival analysis, primary tumour and visceral metastases were significant parameters, while Karnofsky score was only significant in the group including myeloma patients. In multivariate analysis of all seven parameters assessed, primary tumour and visceral metastases were the only significant parameters. Of all seven scoring systems, the original Bauer score and a Bauer score without scoring for pathologic fracture had the best association with survival (P < 0.001). The data of the present study emphasize that the original Bauer score and a modified Bauer score without scoring for pathologic fracture seem to be practicable and highly predictive preoperative scoring systems for patients with spinal metastases. However, decision for or against surgery should never be based alone on a prognostic score but should take symptoms like pain or neurological compromise into account.

Bipedal locomotion of bonnet macaques after spinal cord injury.

PubMed

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

2007-10-01

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

Mu-Opioid Receptors in Ganglia, But Not in Muscle, Mediate Peripheral Analgesia in Rat Muscle Pain.

PubMed

Bagues, Ana; Martín, María Isabel; Higuera-Matas, Alejandro; Esteban-Hernández, Jesús; Ambrosio, Emilio; Sánchez-Robles, Eva María

2018-04-01

Previous studies have demonstrated the participation of peripheral μ-opioid receptors (MOR) in the antinociceptive effect of systemically administered morphine and loperamide in an orofacial muscle pain model, induced by hypertonic saline, but not in a spinally innervated one, in rats. In this study, we determine whether this peripheral antinociceptive effect is due to the activation of MOR localized in the muscle, ganglia, or both. To determine the local antinociceptive effect of morphine and loperamide, 2 models of acute muscle pain (trigeminal and spinal) were used. Also, to study the MOR expression, protein quantification was performed in the trigeminal and spinal ganglia, and in the muscles. The behavioral results show that the intramuscular injection of morphine and loperamide did not exert an antinociceptive effect in either muscle (morphine: P = .63, loperamide: P = .9). On the other hand, MOR expression was found in the ganglia but not in the muscles. This expression was on average 44% higher (95% confidence interval, 33.3-53.9) in the trigeminal ganglia than in the spinal one. The peripheral antinociceptive effect of systemically administered opioids may be due to the activation of MOR in ganglia. The greater expression of MOR in trigeminal ganglia could explain the higher antinociceptive effect of opioids in orofacial muscle pain than in spinal muscle pain. Therefore, peripheral opioids could represent a promising approach for the treatment of orofacial pain.

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

Neurogenin3 restricts serotonergic neuron differentiation to the hindbrain.

PubMed

Carcagno, Abel L; Di Bella, Daniela J; Goulding, Martyn; Guillemot, Francois; Lanuza, Guillermo M

2014-11-12

The development of the nervous system is critically dependent on the production of functionally diverse neuronal cell types at their correct locations. In the embryonic neural tube, dorsoventral signaling has emerged as a fundamental mechanism for generating neuronal diversity. In contrast, far less is known about how different neuronal cell types are organized along the rostrocaudal axis. In the developing mouse and chick neural tube, hindbrain serotonergic neurons and spinal glutamatergic V3 interneurons are produced from ventral p3 progenitors, which possess a common transcriptional identity but are confined to distinct anterior-posterior territories. In this study, we show that the expression of the transcription factor Neurogenin3 (Neurog3) in the spinal cord controls the correct specification of p3-derived neurons. Gain- and loss-of-function manipulations in the chick and mouse embryo show that Neurog3 switches ventral progenitors from a serotonergic to V3 differentiation program by repressing Ascl1 in spinal p3 progenitors through a mechanism dependent on Hes proteins. In this way, Neurog3 establishes the posterior boundary of the serotonergic system by actively suppressing serotonergic specification in the spinal cord. These results explain how equivalent p3 progenitors within the hindbrain and the spinal cord produce functionally distinct neuron cell types. Copyright © 2014 the authors 0270-6474/14/3415223-11$15.00/0.

Preclinical evidence supporting the clinical development of central pattern generator-modulating therapies for chronic spinal cord-injured patients

PubMed Central

2014-01-01

Ambulation or walking is one of the main gaits of locomotion. In terrestrial animals, it may be defined as a series of rhythmic and bilaterally coordinated movement of the limbs which creates a forward movement of the body. This applies regardless of the number of limbs—from arthropods with six or more limbs to bipedal primates. These fundamental similarities among species may explain why comparable neural systems and cellular properties have been found, thus far, to control in similar ways locomotor rhythm generation in most animal models. The aim of this article is to provide a comprehensive review of the known structural and functional features associated with central nervous system (CNS) networks that are involved in the control of ambulation and other stereotyped motor patterns—specifically Central Pattern Generators (CPGs) that produce basic rhythmic patterned outputs for locomotion, micturition, ejaculation, and defecation. Although there is compelling evidence of their existence in humans, CPGs have been most studied in reduced models including in vitro isolated preparations, genetically-engineered mice and spinal cord-transected animals. Compared with other structures of the CNS, the spinal cord is generally considered as being well-preserved phylogenetically. As such, most animal models of spinal cord-injured (SCI) should be considered as valuable tools for the development of novel pharmacological strategies aimed at modulating spinal activity and restoring corresponding functions in chronic SCI patients. PMID:24910602

An In Situ Gelling Drug Delivery System for Improved Recovery after Spinal Cord Injury.

PubMed

Liu, Dongfei; Jiang, Tao; Cai, Weihua; Chen, Jian; Zhang, Hongbo; Hietala, Sami; Santos, Hélder A; Yin, Guoyong; Fan, Jin

2016-06-01

Therapeutic strategies for the spinal cord injury (SCI) are limited by the current available drug delivery techniques. Here, an in situ gelling drug delivery system (DDS), composed of a Poloxamer-407, a 188 mixture-based thermoresponsive hydrogel matrix and, an incorporated therapeutic compound (monosialoganglioside, GM1), is developed for SCI therapy. A low-thoracic hemisection in rats is used as SCI model to evaluate therapeutic efficiency. The GM1-incorporating Poloxamer-407 and 188 polymer solution is converted to a hydrogel (GM1-hydrogel) upon instillation to the injured spinal cord, due to the increased temperature. At body temperature, the thermoresponsive hydrogel prolongs the release of GM1 for about 1 month, due to the superposition of dissolution and swelling (anomalous transport) of the hydrogel matrix. The sustained release of the GM1-hydrogel enables the prolonged residence time of GM1 at the injured spinal cord, decreases the frequency of administration and, consequently, may improve patient compliance. After SCI, the administration of GM1-hydrogel to the lesion site inhibits the apoptotic cell death and glial scar formation, enhances the neuron regeneration, provides neuroprotection to the injured spinal cord, and improves the locomotor recovery. Overall, this study opens future perspectives for the treatment of SCI with a prolonged drug release DDS. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

History of Glial Cell Line-Derived Neurotrophic Factor (GDNF) and Its Use for Spinal Cord Injury Repair.

PubMed

Walker, Melissa J; Xu, Xiao-Ming

2018-06-13

Following an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axonal regeneration. This review focuses on the glial cell line-derived neurotrophic factor (GDNF) and its application, in combination with other factors and cell transplantations, for repairing the injured spinal cord. As studies of recent decades strongly suggest that combinational treatment approaches hold the greatest therapeutic potential for the central nervous system (CNS) trauma, future directions of combinational therapies will also be discussed.

Differential effects of left and right neuropathy on opioid gene expression in lumbar spinal cord.

PubMed

Kononenko, Olga; Mityakina, Irina; Galatenko, Vladimir; Watanabe, Hiroyuki; Bazov, Igor; Gerashchenko, Anna; Sarkisyan, Daniil; Iatsyshyna, Anna; Yakovleva, Tatiana; Tonevitsky, Alex; Marklund, Niklas; Ossipov, Michael H; Bakalkin, Georgy

2018-05-28

The endogenous opioid system (EOS) controls the processing of nociceptive stimuli and is a pharmacological target for opioids. Alterations in expression of the EOS genes under neuropathic pain condition may account for low efficacy of opioid drugs. We here examined whether EOS expression patterns are altered in the lumbar spinal cord of the rats with spinal nerve ligation (SNL) as a neuropathic pain model. Effects of the left- and right-side SNL on expression of EOS genes in the ipsi- and contralateral spinal domains were analysed. The SNL-induced changes were complex and different between the genes; between the dorsal and ventral spinal domains; and between the left and right sides of the spinal cord. Prodynorphin (Pdyn) expression was upregulated in the ipsilateral dorsal domains by each the left and right-side SNL, while changes in expression of μ-opioid receptor (Oprm1) and proenkephalin (Penk) genes were dependent on the SNL side. Changes in expression of the Pdyn and κ-opioid receptor (Oprk1) genes were coordinated between the ipsi- and contralateral sides. Withdrawal response thresholds, indicators of mechanical allodynia correlated negatively with Pdyn expression in the right ventral domain after right side SNL. These findings suggest multiple roles of the EOS gene products in spinal sensitization and changes in motor reflexes, which may differ between the left and right sides. Copyright © 2018. Published by Elsevier B.V.

Impact of H3.3 K27M Mutation on Prognosis and Survival of Grade IV Spinal Cord Glioma on the Basis of New 2016 World Health Organization Classification of the Central Nervous System.

PubMed

Yi, Seong; Choi, Sunkyu; Shin, Dong Ah; Kim, Du Su; Choi, Junjeong; Ha, Yoon; Kim, Keung Nyun; Suh, Chang-Ok; Chang, Jong Hee; Kim, Se Hoon; Yoon, Do Heum

2018-05-01

Spinal cord glioma grade IV is a rare, diffuse midline glioma. H3 K27M-mutant was classified in a different entity in the 2016 World Health Organization (WHO) classification recently. No reports about prognosis of spinal cord glioma grade IV are available yet. To analyze the prognostic factors for spinal cord glioma grade IV. Twenty-five patients with spinal cord glioma of grade IV who underwent surgery in a single institute were selected. All grade IV spinal cord glioma histologically confirmed as glioblastoma or "diffuse midline glioma with H3 K27M-mutant" by the 2016 WHO classification of the central nervous system were included. Basic demographics, treatment modalities, and pathological tumor molecular profiles were investigated for prognosis. Mean age was 39.1 yr; male to female ratio was 18 : 7. Tumor was located in thoracic cord (53.3%), cervical cord (40%), and lumbar area (6.7%). Median overall survival was 37.1 mo; median disease-free survival was 18.5 mo. Treatment modality showed no statistical difference. Only K27M profile showed significant prognostic value, 20 patients (80%) showed K27M mutation positive, K27M mutation patients showed longer overall survival (40.07 mo) than K27M negative patients (11.63 mo, P < .0001), and disease-free survival (20.85 vs 8.72 mo, P = .0241). This study is the first and largest report of the prognosis of primary spinal cord grade IV glioma using the new WHO classification. This study reported survival analysis and prognostic factors, and revealed that H3.3 K27M mutation is not a major poor prognostic factor. Further studies to explore K27M mutations needed for risk stratification and therapy optimization.

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.

"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.

Spinal Cord Injury as a Permanent Consequence of Victimization in Random Violence: A Public Health Perspective.

ERIC Educational Resources Information Center

Anderson, James F.; Dyson, Laronistine; Grandison, Terry

1998-01-01

Traumatic spinal cord injuries resulting from criminal violence is a growing public health concern. Citing the criminal justice system's failure to reduce violence and the costs of treating injuries, a public health-education approach is advocated. Approaches to prevention, gun control, and a comprehensive family policy are discussed. (Author/EMK)

The posterior skeletal thorax: rib-vertebral angle and axial vertebral rotation asymmetries in adolescent idiopathic scoliosis.

PubMed

Burwell, R G; Aujla, R K; Freeman, B J C; Dangerfield, P H; Cole, A A; Kirby, A S; Polak, F J; Pratt, R K; Moulton, A

2008-01-01

The deformity of the ribcage in thoracic adolescent idiopathic scoliosis (AIS) is viewed by most as being secondary to the spinal deformity, though a few consider it primary or involved in curve aggravation. Those who consider it primary ascribe pathogenetic significance to rib-vertebra angle asymmetry. In thoracic AIS, supra-apical rib-vertebra angle differences (RVADs) are reported to be associated with the severity of the Cobb angle. In this paper we attempt to evaluate rib and spinal pathomechanisms in thoracic and thnoracolumbar AIS using spinal radiographs and real-time ultrasound. On the radiographs by costo-vertebral angle asymmetries (rib-vertebral angle differences RVADs, and rib-spinal angle differences RSADs), apical vertebral rotation (AV) and apical vertebral translation (AVT) were measured; and by ultrasound, spine-rib rotation differences (SRRDs) were estimated. RVADs are largest at two and three vertebral levels above the apex where they correlate significantly and positively with Cobb angle and AVT but not AVR. In right thoracic AIS, the cause(s) of the RVA asymmetries is unknown: it may result from trunk muscle imbalance, or from ribs adjusting passively within the constraint of the fourth column of the spine to increasing spinal curvature from whatever cause. Several possible mechanisms may drive axial vertebral rotation including, biplanar spinal asymmetry, relative anterior spinal overgrowth, dorsal shear forces in the presence of normal vertebral axial rotation, asymmetry of rib linear growth, trunk muscle imbalance causing rib-vertebra angle asymmetry weakening the spinal rotation-defending system of bipedal gait, and CNS mechanisms.

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.

“No Clinical Puzzles More Interesting”: Harvey Cushing and Spinal Trauma, The Johns Hopkins Hospital 1896-1912

PubMed Central

Dasenbrock, Hormuzdiyar H.; Pendleton, Courtney; Cohen-Gadol, Aaron A.; Witham, Timothy F.; Gokaslan, Ziya L.; Quinones-Hinojosa, Alfredo; Bydon, Ali

2015-01-01

Although Harvey Cushing played a central role in the establishment of neurosurgery in the United States, his work on the spine remains largely unknown. This article is not only the first time that Cushing's spinal cases while he was at Johns Hopkins have been reported, but also the first time his management of spinal trauma has been described. We report on 12 patients that Cushing treated from 1898 to 1911 who have never been reported before, including blunt and penetrating injuries, complete and incomplete spinal cord lesions, and both immediate and delayed presentations. Cushing performed laminectomies within 24 hours on patients with immediate presentations—both complete and incomplete spinal cord lesions. Among those with delayed presentations, Cushing did laminectomies on patients with incomplete spinal cord injuries. By the end of his tenure at Hopkins, Cushing advocated nonoperative treatment for all patients with complete spinal cord lesions. Four patients died while an inpatient, with meningitis and cystitis leading to the death of 1 and 3 patients, respectively. Cystitis was treated with intravesicular irrigation; an indwelling catheter was placed by a suprapubic cystostomy in four. Cushing was one of the first to report the use of x-ray in a spine patient, in a case that may have been one factor leading to his interest in the nervous system; Cushing also routinely obtained radiographs in those with spinal trauma. These cases illustrate Cushing's dedication to and rapport with his patients, even in the face of a dismal prognosis. PMID:21135734

Effect of nationwide injury prevention programme on serious spinal injuries in New Zealand rugby union: ecological study

PubMed Central

Gianotti, Simon M; Hopkins, Will G; Hume, Patria A

2007-01-01

Objective To investigate the effect of RugbySmart, a nationwide educational injury prevention programme, on the frequency of spinal cord injuries. Design Ecological study. Setting New Zealand rugby union. Participants Population at risk of injury comprised all New Zealand rugby union players. Intervention From 2001, all New Zealand rugby coaches and referees have been required to complete RugbySmart, which focuses on educating rugby participants about physical conditioning, injury management, and safe techniques in the contact phases of rugby. Main outcome measures Numbers of all spinal injuries due to participation in rugby union resulting in permanent disablement in 1976-2005, grouped into five year periods; observed compared with predicted number of spinal injuries in 2001-5. Results Eight spinal injuries occurred in 2001-5, whereas the predicted number was 18.9 (relative rate=0.46, 95% confidence interval 0.19 to 1.14). Only one spinal injury resulted from scrums over the period; the predicted number was 9.0 (relative rate=0.11, 0.02 to 0.74). Corresponding observed and predicted rates for spinal injuries resulting from other phases of play (tackle, ruck, and maul) were 7 and 9.0 (relative rate=0.83, 0.29 to 2.36). Conclusions The introduction of the RugbySmart programme coincided with a reduction in the rate of disabling spinal injuries arising from scrums in rugby union. This study exemplifies the benefit of educational initiatives in injury prevention and the need for comprehensive injury surveillance systems for evaluating injury prevention initiatives in sport. PMID:17513314

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

Inhibitory descending rhombencephalic projections in larval sea lamprey.

PubMed

Valle-Maroto, S M; Fernández-López, B; Villar-Cerviño, V; Barreiro-Iglesias, A; Anadón, R; Rodicio, M Celina

2011-10-27

Lampreys are jawless vertebrates, the most basal group of extant vertebrates. This phylogenetic position makes them invaluable models in comparative studies of the vertebrate central nervous system. Lampreys have been used as vertebrate models to study the neuronal circuits underlying locomotion control and axonal regeneration after spinal cord injury. Inhibitory inputs are key elements in the networks controlling locomotor behaviour, but very little is known about the descending inhibitory projections in lampreys. The aim of this study was to investigate the presence of brain-spinal descending inhibitory pathways in larval stages of the sea lamprey Petromyzon marinus by means of tract-tracing with neurobiotin, combined with immunofluorescence triple-labeling methods. Neurobiotin was applied in the rostral spinal cord at the level of the third gill, and inhibitory populations were identified by the use of cocktails of antibodies raised against glycine and GABA. Glycine-immunoreactive (-ir) neurons that project to the spinal cord were observed in three rhombencephalic reticular nuclei: anterior, middle and posterior. Spinal-projecting GABA-ir neurons were observed in the anterior and posterior reticular nuclei. Double glycine-ir/GABA-ir spinal cord-projecting neurons were only observed in the posterior reticular nucleus, and most glycine-ir neurons did not display GABA immunoreactivity. The present results reveal the existence of inhibitory descending projections from brainstem reticular neurons to the spinal cord, which were analyzed in comparative and functional contexts. Further studies should investigate which spinal cord circuits are affected by these descending inhibitory projections. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

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

PubMed

Jou, I M

2000-08-01

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

Intractable Pruritus After Traumatic Spinal Cord Injury

PubMed Central

Crane, Deborah A; Jaffee, Kenneth M; Kundu, Anjana

2009-01-01

Background: This report describes a young woman with incomplete traumatic cervical spinal cord injury and intractable pruritus involving her dorsal forearm. Method: Case report. Findings: Anatomic distribution of the pruritus corresponded to the dermatomal distribution of her level of spinal cord injury and vertebral fusion. Symptoms were attributed to the spinal cord injury and possible cervical root injury. Pruritus was refractory to all treatments, including topical lidocaine, gabapentin, transcutaneous electrical nerve stimulation, intravenous Bier block, stellate ganglion block, and acupuncture. Conclusions: Further understanding of neuropathic pruritus is needed. Diagnostic workup of intractable pruritus should include advanced imaging to detect ongoing nerve root compression. If diagnostic studies suggest radiculopathy, epidural steroid injection should be considered. Because the autonomic nervous system may be involved in complex chronic pain or pruritic syndromes, sympatholysis via such techniques as stellate ganglion block might be effective. PMID:19777867

Real-time monitoring of spinal cord blood flow with a novel sensor mounted on a cerebrospinal fluid drainage catheter in an animal model.

PubMed

Hayatsu, Yukihiro; Kawamoto, Shunsuke; Matsunaga, Tadao; Haga, Yoichi; Saiki, Yoshikatsu

2014-10-01

The aim of our study was to develop a novel monitoring system for spinal cord blood flow (SCBF) to test the efficacy of the SCBF sensor in an animal model. The sensor system consisted of 2 optical fibers, a pedestal for fiber fixation, and a mirror for the laser reflection and was incorporated into a cerebrospinal fluid drainage catheter. In vivo studies were performed in a swine model (n=10) to measure SCBF during spinal cord ischemia induced by clamping the descending thoracic aorta and supra-aortic neck vessels, when necessary. A temporary low cardiac output model was also created by inflow clamping of the inferior vena cava to analyze the quantitative changes in SCBF during this maneuver. The developed SCBF monitoring catheter placed intrathecally could detect SCBF in all the swine. The SCBF after aortic crossclamping at the fourth intercostal level exhibited diverse changes reproducibly among the swine, with a >25% reduction in SCBF in 5 pigs, an increase in 3, and no significant changes in 2. Consistent reductions were recorded during inferior vena cava occlusion. The mean SCBF decreased by 32% after inferior vena cava occlusion when the cardiac output had decreased by 27%. We have developed a novel SCBF sensor that could detect real-time changes in spinal cord perfusion in a swine model. The device holds promise to detect imminent ischemia or ensure acceptable blood perfusion in the spinal cord and could further enhance our understanding of spinal cord circulation. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Percutaneous Pedicle-Lengthening Osteotomy in Minimal Invasive Spinal Surgery to Treat Degenerative Lumbar Spinal Stenosis: A Single-Center Preliminary Experience.

PubMed

Maugeri, Rosario; Basile, Luigi; Gulì, Carlo; Banco, Aurelia; Giordano, Giovanna; Giugno, Antonella; Graziano, Francesca; Giammalva, Roberto Giuseppe; Iacopino, Domenico Gerardo

2018-06-14

 Lumbar spinal stenosis (LSS) is a narrowing of the spinal canal due to spinal degeneration, and its main clinical symptom is neurogenic claudication. Surgical treatment is pursued for patients who do not improve with conservative care. Patients with symptomatic LSS who also have significant medical comorbidities, although clearly in need of intervention, are unattractive candidates for traditional open lumbar decompressive procedures. Thus it is important to explore minimally invasive surgical techniques to treat select patients with LSS.  This retrospective case series evaluated the clinical and radiographic outcomes of a new minimally invasive procedure to treat LSS: pedicle-lengthening osteotomy using the ALTUM system ((Innovative Surgical Designs, Inc., Bloomington, Indiana, United States). Peri- and postoperative demographic and radiographic data were collected from a clinical series of seven patients with moderate LSS who were > 60 years of age. Clinical outcome was evaluated using visual analog scale (VAS) scores and the spinal canal area on computed tomography scans.  Twelve months after the procedure, scoring revealed a median improvement of 3.7 on the VAS for the back and 6.3 on the VAS for the leg, compared with the preoperative baseline ( p  < 0.05). The postoperative central area of the lumbar canal was significantly increased, by 0.39 cm 2 ; the right and left neural foramina were enlarged by 0.29 cm 2 and 0.47 cm 2 , respectively ( p  < 0.05).  In this preliminary study, the ALTUM system showed a good clinical and radiologic outcome 1 year after surgery. In an older or high-risk population, a short minimally invasive procedure may be beneficial for treating LSS. Georg Thieme Verlag KG Stuttgart · New York.

Crossed reciprocal inhibition evoked by electrical stimulation of the lamprey spinal cord.

PubMed

Fagerstedt, P; Zelenin, P V; Deliagina, T G; Orlovsky, G N; Grillner, S

2000-09-01

Activation of a motoneuron pool is often accompanied by inhibition of the antagonistic pool through a system of reciprocal inhibition between the two parts of the neuronal network controlling the antagonistic pools. In the present study, we describe the activity of such a system in the isolated spinal cord of the lamprey, when a tonic motor output is evoked by extracellular stimulation (0.5-1 s train of pulses, 20 Hz) of either end of the spinal cord. With two electrodes symmetrically positioned in relation to the midline, stimulation with either of them separately elicited prolonged (1-5 s) ipsilateral ventral root activity. Activity could be abolished by stronger, simultaneously applied, stimulation of the contralateral side of the cord, suggesting that reciprocal inhibition between hemisegments operates when a tonic motor output is generated. Simultaneous stimulation of both sides of the spinal cord with a single electrode with a large tip (300-400 microm in diameter), positioned over the anatomical midline, elicited inconsistent right-side, leftside, or bilateral ventral root responses. A minor displacement (10-20 microm) to the left or right from the midline resulted in activation of ipsilateral motoneurons, whereas the contralateral motoneurons were silent. These findings indicate that a small asymmetry in the excitatory drive to the left and right spinal hemisegments can be further amplified by reciprocal inhibition between the hemisegments. Longitudinal splitting of the spinal cord along the midline resulted in reduced reciprocal inhibition between the hemisegments separated by the lesion. The reduction was proportional to the extent of the split. The inhibition was abolished when the split reached nine segments in length. From these experiments, the longitudinal distribution of the commissural axons responsible for inhibition of contralateral motor output could be estimated.

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.

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

Prognostic Factors Influencing the Outcome of 64 Consecutive Patients Undergoing Surgery for Metastatic Melanoma of the Spine.

PubMed

Sellin, Jonathan N; Gressot, Loyola V; Suki, Dima; St Clair, Eric G; Chern, Joshua; Rhines, Laurence D; McCutcheon, Ian E; Rao, Ganesh; Tatsui, Claudio E

2015-09-01

Melanoma metastases to the spine remain a challenge for neurosurgeons. To identify factors associated with survival in a series of patients who underwent spinal surgery for metastatic melanoma. We retrospectively reviewed all patients (n = 64) who received surgical intervention for melanoma metastases to the spine at the University of Texas MD Anderson Cancer Center between July 1993 and March 2012. No patients were excluded from the study, and vital status data were available for all patients. Median overall survival was 5.7 months (95% confidence interval, 2.7-28.7). On univariate survival analysis, diagnosis of spinal metastasis after prior diagnosis of systemic metastasis, higher total spinal disease burden (including but not exclusive to the operative site), presence of progressive systemic disease at the moment of spine surgery, and postoperative complications were associated with poorer overall survival, whereas the presence of only bone metastasis at the moment of surgery was associated with improved overall survival. On multivariate survival analysis, both progressive systemic disease at the moment of spine surgery and total spinal disease burden of ≥3 vertebral levels were significantly associated with worse overall survival (hazard ratio, 6.00; 95% confidence interval, 3.19-11.28; P < .001; and hazard ratio, 2.87; 95% confidence interval, 1.62-5.07; P < .001, respectively). On multivariate analysis, involvement of ≥3 vertebral bodies and progressive systemic disease were associated with worse overall survival. Consideration of these factors should influence surgical decision making in this patient population.

An alternative didactic, functional and topographic systematization of the spinal muscles.

PubMed

de Araújo Baptista, Vivianne Izabelle; Mayer, William Paganini; Eustáquio da Silva, Ricardo; de Vasconcellos Fontes, Ricardo Bragança; da Silva Baptista, Josemberg

2017-09-01

Back muscles are commonly described in a topographically-oriented manner without necessarily following morphological criteria. In this manner, non-standard terms may be employed which convey incorrect morphological concepts and demanding more time from both faculty and students to transmit knowledge. We propose a classification system for spinal muscles incorporating morphological concepts with the goal of facilitating knowledge transfer and suggest the term "spinal muscles". Those muscles were systematically divided and classified in seven strata from anterior to posterior: vertebro-appendicular (VA), transversarium (Tr), deep post-transversarium (DPT), middle post-transversarium (MPT), superficial post-transversarium (SPT), deep spino-appendicular (DSA) and superficial spino-appendicular (SSA). Besides topography and function, this system incorporates innervation and embryological origins of each muscle. The extrinsic (VA, DSA, SSA) or intrinsic (Tr, DPT, MPT, SPT) nature of these muscles in relation to the spine and also the topographic relationship to the transverse process is represented in this system. Specific areas of functional, nervous and developmental transition exist on Tr and DPT strata due to being adjacent to extrinsic strata. We believe this system represents a more modern and concise teaching strategy for back muscles which may be employed partially or fully within any program. We envision its full version may be particularly useful in postgraduate medical training for specialties dealing with the spinal column such as neurosurgery, orthopedic surgery and physical medicine and rehabilitation. Copyright © 2017 Elsevier GmbH. All rights reserved.

Comparison of double intravenous vasopressor automated system using nexfin versus manual vasopressor bolus administration for maintenance of haemodynamic stability during spinal anaesthesia for caesarean delivery: A randomised double-blind controlled trial.

PubMed

Sng, Ban Leong; Du, Wei; Lee, Man Xin; Ithnin, Farida; Mathur, Deepak; Leong, Wan Ling; Sultana, Rehena; Han, Nian-Lin R; Sia, Alex Tiong Heng

2018-05-01

Hypotension is a common side effect of spinal anaesthesia during caesarean delivery and is associated with maternal and foetal adverse effects. We developed an updated double intravenous vasopressor automated (DIVA) system that administers phenylephrine or ephedrine based on continuous noninvasive haemodynamic monitoring using the Nexfin device. The aim of our present study is to compare the performance and reliability of the DIVA system against Manual Vasopressor Bolus administration. A randomised, double-blind controlled trial. Single-centre, KK Women's and Children's Hospital, Singapore. Two hundred and thirty-six healthy women undergoing elective caesarean delivery under spinal anaesthesia. The primary outcome was the incidence of maternal hypotension. The secondary outcome measures were reactive hypertension, total vasopressor requirement and maternal and neonatal outcomes. The DIVA group had a significantly lower incidence of maternal hypotension, with 39.3% (46 of 117) patients having any SBP reading less than 80% of baseline compared with 57.5% (65 of 113) in the manual vasopressor bolus group (P = 0.008). The DIVA group also had fewer hypotensive episodes than the manual vasopressor bolus group (4.67 versus 7.77%; P < 0.0001). There was no difference in the incidence of reactive hypertension or the total vasopressor requirement. The DIVA group had less wobble in system performance. Maternal and neonatal outcomes were similar. The DIVA system achieved better control of maternal blood pressure after spinal anaesthesia than manual vasopressor bolus administration. Clinicaltrials.gov identifier: NCT02277730.

An augmented reality haptic training simulator for spinal needle procedures.

PubMed

Sutherland, Colin; Hashtrudi-Zaad, Keyvan; Sellens, Rick; Abolmaesumi, Purang; Mousavi, Parvin

2013-11-01

This paper presents the prototype for an augmented reality haptic simulation system with potential for spinal needle insertion training. The proposed system is composed of a torso mannequin, a MicronTracker2 optical tracking system, a PHANToM haptic device, and a graphical user interface to provide visual feedback. The system allows users to perform simulated needle insertions on a physical mannequin overlaid with an augmented reality cutaway of patient anatomy. A tissue model based on a finite-element model provides force during the insertion. The system allows for training without the need for the presence of a trained clinician or access to live patients or cadavers. A pilot user study demonstrates the potential and functionality of the system.

Vestibular lesion-induced developmental plasticity in spinal locomotor networks during Xenopus laevis metamorphosis.

PubMed

Beyeler, Anna; Rao, Guillaume; Ladepeche, Laurent; Jacques, André; Simmers, John; Le Ray, Didier

2013-01-01

During frog metamorphosis, the vestibular sensory system remains unchanged, while spinal motor networks undergo a massive restructuring associated with the transition from the larval to adult biomechanical system. We investigated in Xenopus laevis the impact of a pre- (tadpole stage) or post-metamorphosis (juvenile stage) unilateral labyrinthectomy (UL) on young adult swimming performance and underlying spinal locomotor circuitry. The acute disruptive effects on locomotion were similar in both tadpoles and juvenile frogs. However, animals that had metamorphosed with a preceding UL expressed restored swimming behavior at the juvenile stage, whereas animals lesioned after metamorphosis never recovered. Whilst kinematic and electrophysiological analyses of the propulsive system showed no significant differences in either juvenile group, a 3D biomechanical simulation suggested that an asymmetry in the dynamic control of posture during swimming could account for the behavioral restoration observed in animals that had been labyrinthectomized before metamorphosis. This hypothesis was subsequently supported by in vivo electromyography during free swimming and in vitro recordings from isolated brainstem/spinal cord preparations. Specifically, animals lesioned prior to metamorphosis at the larval stage exhibited an asymmetrical propulsion/posture coupling as a post-metamorphic young adult. This developmental alteration was accompanied by an ipsilesional decrease in propriospinal coordination that is normally established in strict left-right symmetry during metamorphosis in order to synchronize dorsal trunk muscle contractions with bilateral hindlimb extensions in the swimming adult. Our data thus suggest that a disequilibrium in descending vestibulospinal information during Xenopus metamorphosis leads to an altered assembly of adult spinal locomotor circuitry. This in turn enables an adaptive compensation for the dynamic postural asymmetry induced by the vestibular imbalance and the restoration of functionally-effective behavior.

Pregabalin Suppresses Spinal Neuronal Hyperexcitability and Visceral Hypersensitivity in the Absence of Peripheral Pathophysiology

PubMed Central

Bannister, Kirsty; Sikandar, Shafaq; Bauer, Claudia S.; Dolphin, Annette C.; Porreca, Frank; Dickenson, Anthony H.

2011-01-01

Background Opioid induced hyperalgesia is recognised in the laboratory and the clinic, generating central hyperexcitability in the absence of peripheral pathology. We investigated pregabalin, indicated for neuropathic pain, and ondansetron, a drug that disrupts descending serotonergic processing in the central nervous system, on spinal neuronal hyperexcitability and visceral hypersensitivity in a rat model of opioid induced hyperalgesia. Methods Sprague-Dawley rats (180-200 g) were implanted with morphine (90μg · μl−1 · hr−1) or saline (0.9% w/v) filled osmotic mini-pumps. On days 7-10 in isoflurane anaesthetized animals we evaluated the effects of (a) systemic pregabalin on spinal neuronal and visceromotor responses and (b) spinal ondansetron on dorsal horn neuronal responses. The messenger RNA levels of α2δ-1, 5HT3A and mu-opioid receptor in the dorsal root ganglia of all animals were analysed. Results In morphine-treated animals the evoked spinal neuronal responses were enhanced to a sub-set of thermal and mechanical stimuli. This activity was attenuated by pregabalin (by at least 71%) and ondansetron (37%), and the visceromotor response to a sub-set of colorectal distension pressures was attenuated by pregabalin (52.8%) (n = 8 for all measures, P < 0.05). Messenger RNA levels were unchanged. Conclusions The inhibitory action of pregabalin in opioid induced hyperalgesia animals is not neuropathy-dependent nor reliant on up-regulation of the α2δ-1 subunit of voltage gated calcium channels, mechanisms proposed essential for pregabalin’s efficacy in neuropathy. In opioid induced hyperalgesia, which extends to colonic distension, a serotonergic facilitatory system may be upregulated creating an environment that’s permissive for pregabalin-mediated analgesia without peripheral pathology. PMID:21602662

Nitric oxide system alteration at spinal cord as a result of perinatal asphyxia is involved in behavioral disabilities: hypothermia as preventive treatment.

PubMed

Dorfman, Verónica Berta; Rey-Funes, Manuel; Bayona, Julio César; López, Ester María; Coirini, Héctor; Loidl, César Fabián

2009-04-01

Perinatal asphyxia (PA) is able to induce sequelae such as spinal spasticity. Previously, we demonstrated hypothermia as a neuroprotective treatment against cell degeneration triggered by increased nitric oxide (NO) release. Because spinal motoneurons are implicated in spasticity, our aim was to analyze the involvement of NO system at cervical and lumbar motoneurons after PA as well as the application of hypothermia as treatment. PA was performed by immersion of both uterine horns containing full-term fetuses in a water bath at 37 degrees C for 19 or 20 min (PA19 or PA20) or at 15 degrees C for 20 min (hypothermia during PA-HYP). Some randomly chosen PA20 rats were immediately exposed for 5 min over grain ice (hypothermia after PA-HPA). Full-term vaginally delivered rats were used as control (CTL). We analyzed NO synthase (NOS) activity, expression and localization by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) reactivity, inducible and neuronal NOS (iNOS and nNOS) by immunohistochemistry, and protein nitrotyrosilation state. We observed an increased NOS activity at cervical spinal cord of 60-day-old PA20 rats, with increased NADPH-d, iNOS, and nitrotyrosine expression in cervical motoneurons and increased NADPH-d in neurons of layer X. Lumbar neurons were not altered. Hypothermia was able to maintain CTL values. Also, we observed decreased forelimb motor potency in the PA20 group, which could be attributed to changes at cervical motoneurons. This study shows that PA can induce spasticity produced by alterations in the NO system of the cervical spinal cord. Moreover, this situation can be prevented by perinatal hypothermia.

Lumbar spinal fusion. Outcome in relation to surgical methods, choice of implant and postoperative rehabilitation.

PubMed

Christensen, Finn Bjarke

2004-10-01

Chronic low back pain (CLBP) has become one of the most common causes of disability in adults under 45 years of age and is consequently one of the most common reasons for early retirement in industrialised societies. Accordingly, CLBP represents an expensive drain on society's resources and is a very challenging area for which a consensus for rational therapy is yet to be established. The spinal fusion procedure was introduced as a treatment option for CLBP more than 70 years ago. However, few areas of spinal surgery have caused so much controversy as spinal fusion. The literature reveals divergent opinions about when fusion is indicated and how it should be performed. Furthermore, the significance of the role of postoperative rehabilitation following spinal fusion may be underestimated. There exists no consensus on the design of a program specific for rehabilitation. Ideally, for any given surgical procedure, it should be possible to identify not only possible complications relative to a surgical procedure, but also what symptoms may be expected, and what pain behaviour may be expected of a particular patient. The overall aims of the current studies were: 1) to introduce patient-based functional outcome evaluation into spinal fusion treatment; 2) to evaluate radiological assessment of different spinal fusion procedures; 3) to investigate the effect of titanium versus stainless steel pedicle screws on mechanical fixation and bone ingrowth in lumbar spinal fusion; 4) to analyse the clinical and radiological outcome of different lumbar spinal fusion techniques; 5) to evaluate complications and re-operation rates following different surgical procedures; and 6) to analyse the effect of different rehabilitation strategies for lumbar spinal fusion patients. The present thesis comprises 9 studies: 2 clinical retrospective studies, 1 clinical prospective case/reference study, 5 clinical randomised prospective studies and 1 animal study (Mini-pigs). In total, 594 patients were included in the investigation from 1979 to 1999. Each had prior to inclusion at least 2 years of CLBP and had therefore been subjected to most of the conservative treatment leg pain, due to localized isthmic spondylolisthesis grades I-II or primary or secondary degeneration. PATIENT-BASED FUNCTIONAL OUTCOME: Patients' self-reported parameters should include the impact of CLBP on daily activity, work and leisure time activities, anxiety/depression, social interests and intensity of back and leg pain. Between 1993 and 2003 approximately 1400 lumbar spinal fusion patients completed the Dallas Pain Questionnaire under prospective design studies. In 1996, the Low Back Pain Rating scale was added to the standard questionnaire packet distributed among spinal fusion patients. In our experience, these tools are valid instruments for clinical assessment of candidates for spinal fusion procedures. It is extremely difficult to interpret radiographs of both lumbar posterolateral fusion and anterior interbody fusion. Plain radiographs are clearly not the perfect media for analysis of spinal fusion, but until new and better diagnostic methods are available for clinical use, radiographs will remain the golden standard. Therefore, the development of a detailed reliable radiographic classification system is highly desirable. The classification used in the present thesis for the evaluation of posteroalteral spinal fusion, both with and without instrumentation, demonstrated good interobserver and intraobserver agreement. The classification showed acceptable reliability and may be one way to improve interstudy and intrastudy correlation of radiologic outcomes after posterolateral spinal fusion. Radiology-based evaluation of anterior lumbar interbody fusion is further complicated when cages are employed. The use of different cage designs and materials makes it almost impossible to establish a standard radiological classification system for anterior fusions. BONE-SCREW INTERFACE: Mechanical binding at the bone-screw interface was significantly greater for titanium pedicle screws than it was for stainless steel. This could be explained by the fact that the titanium screws had superior bone on-growth. There was no correlation between screw removal torques and pull-out strength. Clinically, the use of titanium and titanium-alloy pedicle screws may be preferable for osteoporotic patients and those with decreased osteogenesis. The present series of studies observed significant long-term functional improvement for approximately 70% of patients who had undergone lumbar spinal fusion procedure. Solid fusion as determined from radiographs ranged from 52% to 92% depending on the choice of surgical procedure. The choice of surgical procedure should relate to the diagnosis, as patients with isthmic spondylolisthesis (Grades I and II) are best served with posterolateral fusion without instrumentation, and patients with disc degeneration seem to gain most from instrumented posterolateral fusion or circumferential fusion. The number of perioperative complications increased with the use of pedicle screw systems to support posterolateral fusions and increased further with the use of circumferential fusions. There was no significant association between outcome result and perioperative complications. The risk of reoperation within 2 years after the spinal fusion procedure was, however, significantly lower for those who had received circumferential fusion in comparison to posterolateral fusion with instrumentation. Furthermore, the risk of non-union was found to be significantly lower for patients who had received circumferential fusion as compared to posterolateral fusion with and without instrumentation. The complications of sexual dysfunction and fusion at non-intended levels were found to be significant but without influence on the overall outcome. The patients in the Back-café group performed a succession of many daily tasks significantly better and moreover had less pain compared with both the Video and Training groups 2 years after lumbar spinal fusion. The Video group had significantly greater treatment demands outside the hospital system. This study demonstrates the importance of the inclusion of coping schemes and questions the role of intensive exercises in a rehabilitation program for spinal fusion patients.

Gene therapy approaches for spinal cord injury

NASA Astrophysics Data System (ADS)

Bright, Corinne

As the biomedical engineering field expands, combination technologies are demonstrating enormous potential for treating human disease. In particular, intersections between the rapidly developing fields of gene therapy and tissue engineering hold promise to achieve tissue regeneration. Nonviral gene therapy uses plasmid DNA to deliver therapeutic proteins in vivo for extended periods of time. Tissue engineering employs biomedical materials, such as polymers, to support the regrowth of injured tissue. In this thesis, a combination strategy to deliver genes and drugs in a polymeric scaffold was applied to a spinal cord injury model. In order to develop a platform technology to treat spinal cord injury, several nonviral gene delivery systems and polymeric scaffolds were evaluated in vitro and in vivo. Nonviral vector trafficking was evaluated in primary neuronal culture to develop an understanding of the barriers to gene transfer in neurons and their supporting glia. Although the most efficient gene carrier in vitro differed from the optimal gene carrier in vivo, confocal and electron microscopy of these nonviral vectors provided insights into the interaction of these vectors with the nucleus. A novel pathway for delivering nanoparticles into the nuclei of neurons and Schwann cells via vesicle trafficking was observed in this study. Reporter gene expression levels were evaluated after direct and remote delivery to the spinal cord, and the optimal nonviral vector, dose, and delivery strategy were applied to deliver the gene encoding the basic fibroblast growth factor (bFGF) to the spinal cord. An injectable and biocompatible gel, composed of the amphiphillic polymer poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) was evaluated as a drug and gene delivery system in vitro, and combined with the optimized nonviral gene delivery system to treat spinal cord injury. Plasmid DNA encoding the bFGF gene and the therapeutic NEP1--40 peptide were incorporated in the PEG-PCL-PEG gel and injected into a lesion transecting the main dorsomedial and minor ventral medial corticospinal tract (CST). The degree of collateralization of the transected CST was quantified as an indicator of the regenerative potential of these treatments. At one month post-injury, we observed the robust rostral collateralization of the CST tract in response to the bFGF plasmid-loaded gel. In conclusion, we hope that this platform technology can be applied to the sustained local delivery of other proteins for the treatment of spinal cord injury.

A pilot study on the use of cerebrospinal fluid cell-free DNA in intramedullary spinal ependymoma.

PubMed

Connolly, Ian David; Li, Yingmei; Pan, Wenying; Johnson, Eli; You, Linya; Vogel, Hannes; Ratliff, John; Hayden Gephart, Melanie

2017-10-01

Cerebrospinal fluid (CSF) represents a promising source of cell-free DNA (cfDNA) for tumors of the central nervous system. A CSF-based liquid biopsy may obviate the need for riskier tissue biopsies and serve as a means for monitoring tumor recurrence or response to therapy. Spinal ependymomas most commonly occur in adults, and aggressive resection must be delicately balanced with the risk of injury to adjacent normal tissue. In patients with subtotal resection, recurrence commonly occurs. A CSF-based liquid biopsy matched to the patient's spinal ependymoma mutation profile has potential to be more sensitive then surveillance MRI, but the utility has not been well characterized for tumors of the spinal cord. In this study, we collected matched blood, tumor, and CSF samples from three adult patients with WHO grade II intramedullary spinal ependymoma. We performed whole exome sequencing on matched tumor and normal DNA to design Droplet Digital™ PCR (ddPCR) probes for tumor and wild-type mutations. We then interrogated CSF samples for tumor-derived cfDNA by performing ddPCR on extracted cfDNA. Tumor cfDNA was not reliably detected in the CSF of our cohort. Anatomic sequestration and low grade of intramedullary spinal cord tumors likely limits the role of CSF liquid biopsy.

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

Protective effects of Vitamin C against spinal cord injury-induced renal damage through suppression of NF-κB and proinflammatory cytokines.

PubMed

Wang, Wei-Guo; Xiu, Rui-Juan; Xu, Zhan-Wang; Yin, Yan-Xia; Feng, Yuan; Cao, Xue-Cheng; Wang, Ping-Shan

2015-04-01

Spinal cord injury [SCI] leads to complex cellular and molecular interactions which affects various organ systems. The present study focused on determining the protection offered by Vitamin C against spinal injury-induced kidney damage in wistar rats. The experimental protocol was performed with three groups; Sham, SCI and Vitamin C [20 mg/kg/bw] followed by SCI. The kidney tissue was investigated for oxidative stress parameters [reactive oxygen species, protein carbonyl, sulphydryl content, thiobarbituric acid reactive species [TBARS], and myeloperoxidase activity] and antioxidant status [glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase activity]. Further, inflammation studies were performed by analyzing expression of NF-κB, cycloxygenase-2, iNOS through western blot analysis and inflammatory cytokines by TNF-α and IL-1β levels. The present study shows clear evidence that Vitamin C treatment abrogated spinal injury-induced oxidative stress and inflammatory responses and enhanced the antioxidant status. Thus, the protection offered by Vitamin C against spinal cord injury-induced kidney damage is attributed to its anti-oxidant and anti-inflammatory effects.

Opioid administration following spinal cord injury: Implications for pain and locomotor recovery

PubMed Central

Woller, Sarah A.; Hook, Michelle A.

2013-01-01

Approximately one-third of people with a spinal cord injury (SCI) will experience persistent neuropathic pain following injury. This pain negatively affects quality of life and is difficult to treat. Opioids are among the most effective drug treatments, and are commonly prescribed, but experimental evidence suggests that opioid treatment in the acute phase of injury can attenuate recovery of locomotor function. In fact, spinal cord injury and opioid administration share several common features (e.g. central sensitization, excitotoxicity, aberrant glial activation) that have been linked to impaired recovery of function, as well as the development of pain. Despite these effects, the interactions between opioid use and spinal cord injury have not been fully explored. A review of the literature, described here, suggests that caution is warranted when administering opioids after SCI. Opioid administration may synergistically contribute to the pathology of SCI to increase the development of pain, decrease locomotor recovery, and leave individuals at risk for infection. Considering these negative implications, it is important that guidelines are established for the use of opioids following spinal cord and other central nervous system injuries. PMID:23501709

Peripheral Inflammation Undermines the Plasticity of the Isolated Spinal Cord

PubMed Central

Huie, John R.; Grau, James W.

2009-01-01

Peripheral capsaicin treatment induces molecular changes that sensitize the responses of nociceptive neurons in the spinal dorsal horn. The current studies demonstrate that capsaicin also undermines the adaptive plasticity of the spinal cord, rendering the system incapable of learning a simple instrumental task. In these studies, male rats are transected at the second thoracic vertebra and are tested 24 to 48 hours later. During testing, subjects receive shock to one hindleg when it is extended (controllable stimulation). Rats quickly learn to maintain the leg in a flexed position. Rats that have been injected with capsaicin (1% or 3%) in the hindpaw fail to learn, even when tested on the leg contralateral to the injection. This learning deficit lasts at least 24 hours. Interestingly, training with controllable electrical stimulation prior to capsaicin administration protects the spinal cord against the maladaptive effects. Rats pretrained with controllable stimulation do not display a learning deficit or tactile allodynia. Moreover, controllable stimulation, combined with naltrexone, reverses the capsaicin-induced deficit. These data suggest that peripheral inflammation, accompanying spinal cord injuries, might have an adverse effect on recovery. PMID:18298266

Characterization of Proliferating Neural Progenitors after Spinal Cord Injury in Adult Zebrafish

PubMed Central

Hui, Subhra Prakash; Nag, Tapas Chandra; Ghosh, Sukla

2015-01-01

Zebrafish can repair their injured brain and spinal cord after injury unlike adult mammalian central nervous system. Any injury to zebrafish spinal cord would lead to increased proliferation and neurogenesis. There are presences of proliferating progenitors from which both neuronal and glial loss can be reversed by appropriately generating new neurons and glia. We have demonstrated the presence of multiple progenitors, which are different types of proliferating populations like Sox2+ neural progenitor, A2B5+ astrocyte/ glial progenitor, NG2+ oligodendrocyte progenitor, radial glia and Schwann cell like progenitor. We analyzed the expression levels of two common markers of dedifferentiation like msx-b and vimentin during regeneration along with some of the pluripotency associated factors to explore the possible role of these two processes. Among the several key factors related to pluripotency, pou5f1 and sox2 are upregulated during regeneration and associated with activation of neural progenitor cells. Uncovering the molecular mechanism for endogenous regeneration of adult zebrafish spinal cord would give us more clues on important targets for future therapeutic approach in mammalian spinal cord repair and regeneration. PMID:26630262

Closed-loop neuromodulation of spinal sensorimotor circuits controls refined locomotion after complete spinal cord injury.

PubMed

Wenger, Nikolaus; Moraud, Eduardo Martin; Raspopovic, Stanisa; Bonizzato, Marco; DiGiovanna, Jack; Musienko, Pavel; Morari, Manfred; Micera, Silvestro; Courtine, Grégoire

2014-09-24

Neuromodulation of spinal sensorimotor circuits improves motor control in animal models and humans with spinal cord injury. With common neuromodulation devices, electrical stimulation parameters are tuned manually and remain constant during movement. We developed a mechanistic framework to optimize neuromodulation in real time to achieve high-fidelity control of leg kinematics during locomotion in rats. We first uncovered relationships between neuromodulation parameters and recruitment of distinct sensorimotor circuits, resulting in predictive adjustments of leg kinematics. Second, we established a technological platform with embedded control policies that integrated robust movement feedback and feed-forward control loops in real time. These developments allowed us to conceive a neuroprosthetic system that controlled a broad range of foot trajectories during continuous locomotion in paralyzed rats. Animals with complete spinal cord injury performed more than 1000 successive steps without failure, and were able to climb staircases of various heights and lengths with precision and fluidity. Beyond therapeutic potential, these findings provide a conceptual and technical framework to personalize neuromodulation treatments for other neurological disorders. Copyright © 2014, American Association for the Advancement of Science.

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

PubMed

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

2014-01-01

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

Cervical spondylodiscitis with spinal epidural abscess caused by Aggregatibacter aphrophilus.

PubMed

Pasqualini, Leonella; Mencacci, Antonella; Scarponi, Anna Maria; Leli, Christian; Fabbriciani, Gianluigi; Callarelli, Laura; Schillaci, Giuseppe; Bistoni, Francesco; Mannarino, Elmo

2008-05-01

Spondylodiscitis caused by Aggregatibacter aphrophilus, formerly known as Haemophilus paraphrophilus, is an unusual condition and can be very difficult to diagnose. We report a case of cervical spondylodiscitis complicated by spinal epidural abscess in a 63-year-old woman, without underlying predisposing conditions. The source of infection was identified as a periodontal infection. The patient was successfully treated with systemic antibiotics.

Therapeutic Hypothermia Following Traumatic Spinal Injury: Morphological and Functional Correlates.

DTIC Science & Technology

1999-01-01

oxide synthase inhibitor ( agmatine ) following traumatic spinal cord injury. The major findings of these studies have shown that significant...Similarly, significant differences were observed following systemic administration of agmatine for 14 days post-injury. Unfortunately, no synergistic or...additive effects were achieved when agmatine and hypothermia were combined. Overall, the results support the original hypothesis of this proposal that

Dorsal spinal cord stimulation obtunds the capacity of intrathoracic extracardiac neurons to transduce myocardial ischemia

PubMed Central

Ardell, Jeffrey L.; Cardinal, René; Vermeulen, Michel; Armour, J. Andrew

2009-01-01

Populations of intrathoracic extracardiac neurons transduce myocardial ischemia, thereby contributing to sympathetic control of regional cardiac indices during such pathology. Our objective was to determine whether electrical neuromodulation using spinal cord stimulation (SCS) modulates such local reflex control. In 10 anesthetized canines, middle cervical ganglion neurons were identified that transduce the ventricular milieu. Their capacity to transduce a global (rapid ventricular pacing) vs. regional (transient regional ischemia) ventricular stress was tested before and during SCS (50 Hz, 0.2 ms duration at 90% MT) applied to the dorsal aspect of the T1 to T4 spinal cord. Rapid ventricular pacing and transient myocardial ischemia both activated cardiac-related middle cervical ganglion neurons. SCS obtunded their capacity to reflexly respond to the regional ventricular ischemia, but not rapid ventricular pacing. In conclusion, spinal cord inputs to the intrathoracic extracardiac nervous system obtund the latter's capacity to transduce regional ventricular ischemia, but not global cardiac stress. Given the substantial body of literature indicating the adverse consequences of excessive adrenergic neuronal excitation on cardiac function, these data delineate the intrathoracic extracardiac nervous system as a potential target for neuromodulation therapy in minimizing such effects. PMID:19515981

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.

Idiopathic normal pressure hydrocephalus: theoretical concept of a spinal etiology.

PubMed

Hamlat, Abderrahmane; Abderrahmane, Hamlat; Sid-Ahmed, Seddik; Seddik, Sid-Ahmed; Adn, Mahmoudreza; Mahmoudreza, Adn; Askar, Brahim; Brahim, Askar; Pasqualini, Edouardo; Edouardo, Pasqualini

2006-01-01

Normal pressure hydrocephalus (NPH) is an adult syndrome characterised by a combination of gait disturbance, varying degrees of cognitive decline, urinary incontinence, ventricular enlargement and normal mean intracranial pressure. Since this syndrome was first described, its pathophysiology has been a matter of great debate, although it is now considered that NPH could be divided into two groups: cases with unknown etiology (idiopathic normal pressure hydrocephalus, or INPH) and those which develop from several known causes (such as trauma, meningitis or subarachnoid haemorrhage). The pathophysiology of INPH is still unclear and a matter of debate. In this manuscript, the current pathophysiological conditions of INPH are analysed and the authors put forward the theory that the disease is a dynamic syndrome which occurs in patients who have suffered a significant loss of spinal compliance over time. Consequently, intracranial pressure increases more during systole in INPH patients because it cannot be compensated for by the escape of CSF into the spinal canal as effectively, due to the reduced volume or lack of distension of the spinal canal. This leads to an increase in ventricular size and causes cumulative brain damage over a long period of time and accounts for the slow, progressive nature of NPH. The loss of spinal compliance with age is fundamental to the proposed theory which provides a theoretical justification for studying the spinal canal in INPH and investigating the relationship between the progressive narrowing of the spinal canal and the compensating ability of the craniospinal system.

Pathological lesions in the central nervous system and peripheral tissues of ddY mice with street rabies virus (1088 strain).

PubMed

Kimitsuki, Kazunori; Yamada, Kentaro; Shiwa, Nozomi; Inoue, Satoshi; Nishizono, Akira; Park, Chun-Ho

2017-06-10

Most studies on rabies virus pathogenesis in animal models have employed fixed rabies viruses, and the results of those employing street rabies viruses have been inconsistent. Therefore, to clarify the pathogenesis of street rabies virus (1088 strain) in mice, 10 6 focus forming units were inoculated into the right hindlimb of ddY mice (6 weeks, female). At 3 days postinoculation (DPI), mild inflammation was observed in the hindlimb muscle. At 5 DPI, ganglion cells in the right lumbosacral spinal dorsal root ganglia showed chromatolysis. Axonal degeneration and inflammatory cells increased with infection progress in the spinal dorsal horn and dorsal root ganglia. Right hindlimb paralysis was observed from 7 DPI, which progressed to quadriparalysis. However, no pathological changes were observed in the ventral horn and root fibers of the spinal cord. Viral antigen was first detected in the right hindlimb muscle at 3 DPI, followed by the right lumbosacral dorsal root ganglia, dorsal horn of spinal cord, left red nuclei, medulla oblongata and cerebral cortex (M1 area) at 5 DPI. These results suggested that the 1088 virus ascended the lumbosacral spinal cord via mainly afferent fibers at early stage of infection and moved to cerebral cortex (M1 area) using descending spinal tract. Additionally, we concluded that significant pathological changes in mice infected with 1088 strain occur in the sensory tract of the spinal cord; this selective susceptibility results in clinical features of the disease.

Risk and Protective Factors for Cause-Specific Mortality After Spinal Cord Injury.

PubMed

Krause, James S; Cao, Yue; DeVivo, Michael J; DiPiro, Nicole D

2016-10-01

To investigate the association of multiple sets of risk and protective factors (biographic and injury, socioeconomic, health) with cause-specific mortality after spinal cord injury (SCI). Retrospective analysis of a prospectively created cohort. Spinal Cord Injury Model Systems facilities. Adults (N=8157) with traumatic SCI who were enrolled in a model systems facility after 1973 and received follow-up evaluation that included all study covariates (between November 1, 1995 and October 31, 2006). Not applicable. All-cause mortality was determined using the Social Security Death Index as of January 1, 2014. Causes of death were obtained from the National Death Index and classified as infective and parasitic diseases, neoplasms, respiratory system diseases, heart and blood vessel diseases, external causes, and other causes. Competing risk analysis, with time-dependent covariates, was performed with hazard ratios (HRs) for each cause of death. The HRs for injury severity indicators were highest for deaths due to respiratory system diseases (highest HR for injury level C1-4, 4.84) and infective and parasitic diseases (highest HR for American Spinal Injury Association Impairment Scale grade A, 5.70). In contrast, injury level and American Spinal Injury Association Impairment Scale grade were relatively unrelated to death due to neoplasms and external causes. Of the socioeconomic indicators, education and income were significantly predictive of a number of causes of death. Pressure ulcers were the only 1 of 4 secondary health condition indicators consistently related to cause of death. Injury severity was related to mortality due to infective disease and respiratory complications, suggesting that those with the most severe SCI should be targeted for prevention of these causes. Socioeconomic and health factors were more broadly related to a number of causes of death. Intervention strategies that enhance socioeconomic status and health may also result in reduced mortality due to multiple causes. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

The importance of the descending monoamine system for the pain experience and its treatment

PubMed Central

Dickenson, Anthony H

2009-01-01

Brainstem and midbrain areas engage descending facilitatory and inhibitory neurones to potentiate or suppress the passage of sensory inputs from spinal loci to the brain. The balance between descending controls, both excitatory and inhibitory, can be altered in various pain states and can critically determine the efficacy of certain analgesic drugs. There is good evidence for a prominent α2 adrenoceptor-mediated inhibitory system and for 5-HT3 receptor-mediated excitatory control of spinal cord activity that originates in supraspinal areas. Given the multiple roles of these transmitters in pain and functions such as sleep, depression, and anxiety, the link between spinal and supraspinal processing of noxious inputs (via the monoamine transmitters) could be pivotal for linking the sensory and affective components of pain and their common co-morbidities, and also may potentially explain differences in pain scores and treatment outcomes in the patient population. PMID:20948695

Outcomes in Treatment for Intradural Spinal Cord Ependymomas

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

Volpp, P. Brian; Han, Khanh; Kagan, A. Robert

2007-11-15

Purpose: Spinal cord ependymomas are rare tumors, accounting for <2% of all primary central nervous system tumors. This study assessed the treatment outcomes for patients diagnosed with spinal cord ependymomas within the Southern California Kaiser Permanente system. Methods and Materials: We studied 23 patients treated with surgery with or without external beam radiotherapy (EBRT). The local and distant control rates and overall survival rates were determined. Results: The overall local control, overall recurrence, and 9-year overall survival rate was 96%, 17.4%, and 63.9%, respectively. Conclusions: The results of our study indicate that en bloc gross total resection should be themore » initial treatment, with radiotherapy reserved primarily for postoperative cases with unfavorable characteristics such as residual tumor, anaplastic histologic features, or piecemeal resection. Excellent local control and overall survival rates can be achieved using modern microsurgical techniques, with or without local radiotherapy.« less

Responses of neuromuscular systems under gravity or microgravity environment.

PubMed

Ishihara, Akihiko; Kawano, Fuminori; Wang, Xiao Dong; Ohira, Yoshinobu

2004-11-01

Hindlimb suspension of rats induces induces fiber atrophy and type shift of muscle fibers. In contrast, there is no change in the cell size or oxidative enzyme activity of spinal motoneurons innervating muscle fibers. Growth-related increases in the cell size of muscle fibers and their spinal motoneurons are inhibited by hindlimb suspension. Exposure to microgravity induces atrophy of fibers (especially slow-twitch fibers) and shift of fibers from slow- to fast-twitch type in skeletal muscles (especially slow, anti-gravity muscles). In addition, a decrease in the oxidative enzyme activity of spinal motoneurons innervating slow-twitch fibers and of sensory neurons in the dorsal root ganglion is observed following exposure to microgravity. It is concluded that neuromuscular activities are important for maintaining metabolism and function of neuromuscular systems at an early postnatal development and that gravity effects both efferent and afferent neural pathways.

The lifetime cost of spinal cord injury in Ontario, Canada: A population-based study from the perspective of the public health care payer.

PubMed

Chan, Brian Chun-Fai; Cadarette, Suzanne M; Wodchis, Walter P; Krahn, Murray D; Mittmann, Nicole

2018-06-20

To determine the publicly funded health care system lifetime cost-of-illness of spinal cord injury (SCI) from the perspective of the Ontario Ministry of Health and Long-term Care. Individuals hospitalized for their first SCI between the years 2005 and 2011 were identified and their health care costs were calculated using Ontario administrative health care data. From this information, lifetime costs were estimated using phase-based costing methods. The spinal cord injured cohort was matched to a non-spinal cord injured using propensity score matching. Net costs were determined by calculating the difference in costs between the two matched groups. Net costs were also presented for subgroups stratified by demographic characteristics. A total of 1,716 individuals with SCI were identified and matched in our study. The net lifetime cost of SCI was $336,000 per person. Much of the costs were observed in the first year post-SCI. The lifetime cost of SCI for individuals with a concurrent pressure ulcer at the initial hospitalization rises to $479,600. Costs were also higher for individuals with cervical or thoracic injury or requiring inpatient rehabilitation. Spinal cord injury is a substantial burden to the health care system. Our results are limited to the direct health care costs from the publicly funded health care payer perspective. Further analysis with a broader perspective is needed to understand the full economic impact of this catastrophic condition.

[HEART RHYTHM VARIABILITY ANALYSIS AND ASSESSMENT OF THE SPINAL PAIN SYNDROME DURING DRY IMMERSION].

PubMed

Sun, I; Voronkov, Yu I; Ardashev, V N; Glukhova, S I

2015-01-01

The spinal pain syndrome appears in cosmonauts on both short and long-duration missions. This untoward factor may affect body systems functioning and complicate the successful accomplishment of space mission. Purpose of the investigation was to examine the lumbar spine and to elucidate whether its condition relates to the spinal pain development and changes in heart rate variability (HRV) in the microgravity environment. The experiment was conducted in dry immersion as a method of microgravity effects simulation. It was shown that in dry immersion locomotion reproduces the patterns peculiar for significant gravitational unloading. Spinal pain intensity, angles and heights of the lumbar intervertebral discs and HRV were measured in 19 selected volunteers. During the experiment, all the volunteers developed pains in the back that abated gradually. Pain dependence on the height of intervertebral discs and cardiac regulatory mechanisms were investigated.

Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury

PubMed Central

Keefe, Kathleen M.; Sheikh, Imran S.; Smith, George M.

2017-01-01

Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI). We focus on nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord. PMID:28273811

Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury.

PubMed

Keefe, Kathleen M; Sheikh, Imran S; Smith, George M

2017-03-03

Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI). We focus on nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord.

Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury.

PubMed

Fairbanks, C A; Schreiber, K L; Brewer, K L; Yu, C G; Stone, L S; Kitto, K F; Nguyen, H O; Grocholski, B M; Shoeman, D W; Kehl, L J; Regunathan, S; Reis, D J; Yezierski, R P; Wilcox, G L

2000-09-12

Antagonists of glutamate receptors of the N-methyl-d-aspartate subclass (NMDAR) or inhibitors of nitric oxide synthase (NOS) prevent nervous system plasticity. Inflammatory and neuropathic pain rely on plasticity, presenting a clinical opportunity for the use of NMDAR antagonists and NOS inhibitors in chronic pain. Agmatine (AG), an endogenous neuromodulator present in brain and spinal cord, has both NMDAR antagonist and NOS inhibitor activities. We report here that AG, exogenously administered to rodents, decreased hyperalgesia accompanying inflammation, normalized the mechanical hypersensitivity (allodynia/hyperalgesia) produced by chemical or mechanical nerve injury, and reduced autotomy-like behavior and lesion size after excitotoxic spinal cord injury. AG produced these effects in the absence of antinociceptive effects in acute pain tests. Endogenous AG also was detected in rodent lumbosacral spinal cord in concentrations similar to those previously detected in brain. The evidence suggests a unique antiplasticity and neuroprotective role for AG in processes underlying persistent pain and neuronal injury.

Long-Distance Axonal Growth from Human Induced Pluripotent Stem Cells After Spinal Cord Injury

PubMed Central

Lu, Paul; Woodruff, Grace; Wang, Yaozhi; Graham, Lori; Hunt, Matt; Wu, Di; Boehle, Eileen; Ahmad, Ruhel; Poplawski, Gunnar; Brock, John; Goldstein, Lawrence S. B.; Tuszynski, Mark H.

2014-01-01

Human induced pluripotent stem cells (iPSCs) from a healthy 86 year-old male were differentiated into neural stem cells and grafted into adult immunodeficient rats after spinal cord injury. Three months after C5 lateral hemisections, iPSCs survived and differentiated into neurons and glia, and extended tens of thousands of axons from the lesion site over virtually the entire length of the rat central nervous system. These iPSC-derived axons extended through adult white matter of the injured spinal cord, frequently penetrating gray matter and forming synapses with rat neurons. In turn, host supraspinal motor axons penetrated human iPSC grafts and formed synapses. These findings indicate that intrinsic neuronal mechanisms readily overcome the inhibitory milieu of the adult injured spinal cord to extend many axons over very long distances; these capabilities persist even in neurons reprogrammed from very aged human cells. PMID:25123310

Orofacial inflammatory pain affects the expression of MT1 and NADPH-d in rat caudal spinal trigeminal nucleus and trigeminal ganglion

PubMed Central

Huang, Fang; He, Hongwen; Fan, Wenguo; Liu, Yongliang; Zhou, Hongyu; Cheng, Bin

2013-01-01

Very little is known about the role of melatonin in the trigeminal system, including the function of melatonin receptor 1. In the present study, adult rats were injected with formaldehyde into the right vibrissae pad to establish a model of orofacial inflammatory pain. The distribution of melatonin receptor 1 and nicotinamide adenine dinucleotide phosphate diaphorase in the caudal spinal trigeminal nucleus and trigeminal ganglion was determined with immunohistochemistry and histochemistry. The results show that there are significant differences in melatonin receptor 1 expression and nicotinamide adenine dinucleotide phosphate diaphorase expression in the trigeminal ganglia and caudal spinal nucleus during the early stage of orofacial inflammatory pain. Our findings suggest that when melatonin receptor 1 expression in the caudal spinal nucleus is significantly reduced, melatonin's regulatory effect on pain is attenuated. PMID:25206619

Risk factors of non-specific spinal pain in childhood.

PubMed

Szita, Julia; Boja, Sara; Szilagyi, Agnes; Somhegyi, Annamaria; Varga, Peter Pal; Lazary, Aron

2018-05-01

Non-specific spinal pain can occur at all ages and current evidence suggests that pediatric non-specific spinal pain is predictive for adult spinal conditions. A 5-year long, prospective cohort study was conducted to identify the lifestyle and environmental factors leading to non-specific spinal pain in childhood. Data were collected from school children aged 7-16 years, who were randomly selected from three different geographic regions in Hungary. The risk factors were measured with a newly developed patient-reported questionnaire (PRQ). The quality of the instrument was assessed by the reliability with the test-retest method. Test (N = 952) and validity (N = 897) datasets were randomly formed. Risk factors were identified with uni- and multivariate logistic regression models and the predictive performance of the final model was evaluated using the receiver operating characteristic (ROC) method. The final model was built up by seven risk factors for spinal pain for days; age > 12 years, learning or watching TV for more than 2 h/day, uncomfortable school-desk, sleeping problems, general discomfort and positive familiar medical history (χ 2  = 101.07; df = 8; p < 0.001). The probabilistic performance was confirmed with ROC analysis on the test and validation cohorts (AUC = 0.76; 0.71). A simplified risk scoring system showed increasing possibility for non-specific spinal pain depending on the number of the identified risk factors (χ 2  = 65.0; df = 4; p < 0.001). Seven significant risk factors of non-specific spinal pain in childhood were identified using the new, easy to use and reliable PRQ which makes it possible to stratify the children according to their individual risk. These slides can be retrieved under Electronic Supplementary Material.

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.

Involvement of p38 MAPK activation mediated through AT1 receptors on spinal astrocytes and neurons in angiotensin II- and III-induced nociceptive behavior in mice.

PubMed

Nemoto, Wataru; Ogata, Yoshiki; Nakagawasai, Osamu; Yaoita, Fukie; Tadano, Takeshi; Tan-No, Koichi

2015-12-01

We have previously demonstrated the possibility that angiotensin (Ang) II and its N-terminal metabolite Ang (1-7) act as neurotransmitters and/or neuromodulators in the spinal transmission of nociceptive information. Ang III, which is a C-terminal metabolite of Ang II, can also act on AT1 receptors, but its role in spinal nociceptive transmission remains unclear. Therefore, we examined the role of Ang III on the spinal nociceptive system in comparison with that of Ang II. Intrathecal (i.t.) administration of Ang III into mice produced a nociceptive behavior, which was dose-dependently inhibited by the co-administration of the AT1 receptor antagonist losartan and the p38 MAPK inhibitor SB203580, but not by the AT2 receptor antagonist PD123319, MEK1/2 inhibitor U0126 and JNK inhibitor SP600125. In addition, Ang III increased the phosphorylation of p38 MAPK in the dorsal lumbar spinal cord, which was inhibited by losartan. These effects were similar to those of observed with Ang II. The nociceptive behavior produced by Ang II or III was also attenuated by the administration of the astrocytic inhibitor L-α-aminoadipic acid, but not by the microglial inhibitor minocycline. Double immunohistochemical staining showed that spinal AT1 receptors were expressed on neurons and astrocytes, and that i.t. administration of either Ang II or III phosphorylated p38 MAPK in both spinal astrocytes and neurons. These results indicate that Ang III produces nociceptive behavior similar to Ang II, and suggest that the phosphorylation of p38 MAPK mediated through AT1 receptors on spinal astrocytes and neurons contributes to Ang II- and III-induced nociceptive behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Selective ablation of dorsal horn NK1 expressing cells reveals a modulation of spinal alpha2-adrenergic inhibition of dorsal horn neurones.

PubMed

Rahman, Wahida; Suzuki, Rie; Hunt, Stephen P; Dickenson, Anthony H

2008-06-01

Activity in descending systems from the brainstem modulates nociceptive transmission through the dorsal horn. Intrathecal injection of the neurotoxin saporin conjugated to SP (SP-SAP) into the lumbar spinal cord results in the selective ablation of NK(1) receptor expressing (NK(1)+ve) neurones in the superficial dorsal horn (lamina I/III). Loss of these NK(1)+ve neurones attenuates excitability of deep dorsal horn neurones due to a disruption of both intrinsic spinal circuits and a spino-bulbo-spinal loop, which activates a descending excitatory drive, mediated through spinal 5HT(3) receptors. Descending inhibitory pathways also modulate spinal activity and hence control the level of nociceptive transmission relayed to higher centres. To ascertain the spinal origins of the major descending noradrenergic inhibitory pathway we studied the effects of a selective alpha2-adrenoceptor antagonist, atipamezole, on neuronal activity in animals pre-treated with SP-SAP. Intrathecal application of atipamezole dose dependently facilitated the mechanically evoked neuronal responses of deep dorsal horn neurones to low intensity von Frey hairs (5-15 g) and noxious thermal (45-50 degrees C) evoked responses in SAP control animals indicating a physiological alpha2-adrenoceptor control. This facilitatory effect of atipamezole was lost in the SP-SAP treated group. These data suggest that activity within noradrenergic pathways have a dependence on dorsal horn NK(1)+ve cells. Further, noradrenergic descending inhibition may in part be driven by lamina I/III (NK(1)+ve) cells, and mediated via spinal alpha2-adrenoceptor activation. Since the same neuronal population drives descending facilitation and inhibition, the reduced excitability of lamina V/VI WDR neurones seen after loss of these NK(1)+ve neurones indicates a dominant role of descending facilitation.

Rostral ventromedial medulla control of spinal sensory processing in normal and pathophysiological states.

PubMed

Bee, L A; Dickenson, A H

2007-07-13

Complex networks of pathways project from various structures in the brain to modulate spinal processing of sensory input in a top-down fashion. The rostral ventromedial medulla (RVM) in the brainstem is one major final common output of this endogenous modulatory system and is involved in the relay of sensory information between the spinal cord and brain. The net output of descending neurons that exert inhibitory and facilitatory effects will determine whether neuronal activity in the spinal cord is increased or decreased. By pharmacologically blocking RVM activity with the local anesthetic lignocaine, and then measuring evoked responses of dorsal horn neurons to a range of applied peripheral stimuli, our aim was to determine the prevailing descending influence operating in normal anesthetized animals and animals with experimental neuropathic pain. The injection of 0.8 microl 2% lignocaine into the RVM caused a reduction in deep dorsal horn neuronal responses to electrical and natural stimuli in 64% of normal animals and in 81% of spinal-nerve-ligated (SNL) animals. In normal animals, responses to noxious input were predominantly reduced, while in SNL animals, reductions in spinal cord activity induced by intra-RVM lignocaine further included responses to non-noxious stimuli. This suggests that in terms of activity at least, if not number, descending facilitations are the predominant RVM influence that impacts the spinal cord in normal animals. Moreover, the increase in the proportion of neurons showing a post-lignocaine reduction in dorsal horn activity in SNL rats suggests that the strength of these facilitatory influences increases after neuropathy. This predominant inhibitory spinal effect following the injection of lignocaine into the RVM may be due to blockade of facilitatory On cells.

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

Epidural application of spinal instrumentation particulate wear debris: a comprehensive evaluation of neurotoxicity using an in vivo animal model.

PubMed

Cunningham, Bryan W; Hallab, Nadim J; Hu, Nianbin; McAfee, Paul C

2013-09-01

The introduction and utilization of motion-preserving implant systems for spinal reconstruction served as the impetus for this basic scientific investigation. The effect of unintended wear particulate debris resulting from micromotion at spinal implant interconnections and bearing surfaces remains a clinical concern. Using an in vivo rabbit model, the current study quantified the neural and systemic histopathological responses following epidural application of 11 different types of medical-grade particulate wear debris produced from spinal instrumentation. A total of 120 New Zealand White rabbits were equally randomized into 12 groups based on implant treatment: 1) sham (control), 2) stainless steel, 3) titanium alloy, 4) cobalt chromium alloy, 5) ultra-high molecular weight polyethylene (UHMWPe), 6) ceramic, 7) polytetrafluoroethylene, 8) polycarbonate urethane, 9) silicone, 10) polyethylene terephthalate, 11) polyester, and 12) polyetheretherketone. The surgical procedure consisted of a midline posterior approach followed by resection of the L-6 spinous process and L5-6 ligamentum flavum, permitting interlaminar exposure of the dural sac. Four milligrams of the appropriate treatment material (Groups 2-12) was then implanted onto the dura in a dry, sterile format. All particles (average size range 0.1-50 μm in diameter) were verified to be endotoxin free prior to implantation. Five animals from each treatment group were sacrificed at 3 months and 5 were sacrificed at 6 months postoperatively. Postmortem analysis included epidural cultures and histopathological assessment of local and systemic tissue samples. Immunocytochemical analysis of the spinal cord and overlying epidural fibrosis quantified the extent of proinflammatory cytokines (tumor necrosis factor-α, tumor necrosis factor-β, interleukin [IL]-1α, IL-1β, and IL-6) and activated macrophages. Epidural cultures were negative for nearly all cases, and there was no evidence of particulate debris or significant histopathological changes in the systemic tissues. Gross histopathological examination demonstrated increased levels of epidural fibrosis in the experimental treatment groups compared with the control group. Histopathological evaluation of the epidural fibrous tissues showed evidence of a histiocytic reaction containing phagocytized inert particles and foci of local inflammatory reactions. At 3 months, immunohistochemical examination of the spinal cord and epidural tissues demonstrated upregulation of IL-6 in the groups in which metallic and UHMWPe debris were implanted (p < 0.05), while macrophage activity levels were greatest in the stainless-steel and UHMWPe groups (p < 0.05). By 6 months, the levels of activated cytokines and macrophages in nearly all experimental cases were downregulated and not significantly different from those of the operative controls (p > 0.05). The spinal cord had no evidence of lesions or neuropathology. However, multiple treatments in the metallic groups exhibited a mild, chronic macrophage response to particulate debris, which had diffused intrathecally. Epidural application of spinal instrumentation particulate wear debris elicits a chronic histiocytic reaction localized primarily within the epidural fibrosis. Particles have the capacity to diffuse intrathecally, eliciting a transient upregulation in macrophage/cytokine activity response within the epidural fibrosis. Overall, based on the time periods evaluated, there was no evidence of an acute neural or systemic histopathological response to the materials included in the current project.

When and how to operate on spondylodiscitis: a report of 13 patients.

PubMed

Mavrogenis, Andreas F; Igoumenou, Vasilis; Tsiavos, Konstantinos; Megaloikonomos, Panayiotis; Panagopoulos, Georgios N; Vottis, Christos; Giannitsioti, Efthymia; Papadopoulos, Antonios; Soultanis, Konstantinos C

2016-01-01

Conflicting reports exist regarding the surgical indications, timing, approach, staged or not operation, and spinal instrumentation for patients with spondylodiscitis. Therefore, we performed this study to evaluate the outcome of a series of patients with spondylodiscitis aiming to answer when and how to operate on these patients. We retrospectively studied the files of 153 patients with spondylodiscitis treated at our institution from 2002 to 2012. The approach included MR imaging of the infected spine, isolation of the pathogen with blood cultures and/or biopsy, and further conservative or surgical treatment. The mean follow-up was 6 years (range 1-13 years). We evaluated the indications, timing (when), and methods (how) for surgical treatment, and the clinical outcome of these patients. Orthopedic surgical treatment was necessary for 13 of the 153 patients (8.5 %). These were patients with low access to healthcare systems because of low socioeconomic status, third-country migrants, prisoners or intravenous drug use, patients in whom a bacterial isolate documentation was necessary, and patients with previous spinal operations. The most common pathogen was Mycobacterium tuberculosis. The surgical indications included deterioration of the neurological status (11 patients), need for bacterial isolate (10 patients), septicemia due to no response to antibiotics (five patients), and/or spinal instability (three patients). An anterior vertebral approach was more commonly used. Nine of the 13 patients had spinal instrumentation in the same setting. Improvement or recovery of the neurological status was observed postoperatively in all patients with preoperative neurological deficits. Postoperatively, two patients deceased from pulmonary infection and septicemia, and heart infarction. At the last follow-up, patients who were alive were asymptomatic; ten patients were neurologically intact, and one patient experienced paraparesis. Imaging showed spinal fusion, without evidence of recurrent spondylodiscitis. Complications related to the spinal instrumentation were not observed in the respective patients. Conservative treatment is the standard for spondylodiscitis. Physicians should be alert for Mycobacterium tuberculosis spondylitis because of the low access to healthcare systems of patients with low social and economic status. Surgical indications include obtaining tissue sample for diagnosis, occurrence or progression of neurological symptoms, failure of conservative treatment, large anterior abscesses, and very extensive disease. Thorough debridement of infected tissue and spinal stability is paramount. The anterior approach provides direct access and improved exposure to the most commonly affected part of the spine. Spinal instrumentation is generally recommended for optimum spinal stability and fusion, without any implant-related complications.

Bulbospinal substance P and sympathetic regulation of the cardiovascular system: a review.

PubMed

Helke, C J; Charlton, C G; Keeler, J R

1985-01-01

The neurotransmitter role of substance P in mediating sympathoexcitatory effects in the spinal cord and cardiovascular effects elicited from the ventral medulla is presented. SP neurons located in the ventral medulla project to the intermediolateral cell column (IML) of the thoracic spinal cord. Intrathecal administration of a SP analog excites sympathetic outflow to the cardiovascular system. Likewise, activation of the ventral medulla results in sympathetically mediated increases in blood pressure and heart rate which are blocked with SP antagonists. The IML contained a high density of SP binding sites through which the peptide likely exerts its sympathoexcitatory influence on the cardiovascular system.

Changes in echogenicity of spinal subarachnoid space associated with intracranial hemorrhage: new observations.

PubMed

Rudas, G; Varga, E; Méder, U; Pataki, M; Taylor, G A

2000-11-01

The role of subarachnoid blood and secondary, sterile inflammation in the pathogenesis of posthemorrhagic hydrocephalus (PHH) is not well understood. The aims of this study were to study the frequency and rate of spread of blood into the spinal subarachnoid space (SSS) and to evaluate the relationship of this finding and PHH. Nine premature babies with major intracerebral hemorrhage (ICH, grade 3 or higher), and ten premature infants with minor ICH (grade 1) or no evidence of ICH (control group) were identified and underwent serial cranial and spinal sonography at the time of initial diagnosis, 12-24 h after the ICH and weekly thereafter for at least 9 weeks. Sagittal and axial scans of the thoracolumbar spine were obtained and evaluated for the presence of echogenic debris in the dorsal SSS. Six additional patients who had cranial and spinal sonography died within the 1st week of life and underwent post-mortem examinations. The SSS was echo-free (normal) in all cases at the time of initial sonographic diagnosis of ICH. Within 24 h, all babies with major ICH had developed increased echogenicity of the cervical and thoracic SSS. Echogenicity of the SSS decreased gradually over several weeks. Although transient ventricular dilatation was present in every patient, only one patient had rapidly progressive PHH requiring shunt placement. Transient cysts of the cervicothoracic subarachnoid space were identified in two patients 6-7 weeks after ICH. The subarachnoid space remained echo-free in all control infants At autopsy, all four infants with echogenic spinal debris had blood or blood products in the spinal subarachnoid space, whereas two infants with echo-free spinal images did not. Spread of blood from the ventricular system into the spinal subarachnoid space after ICH is common and can be seen within 24 h of initial ICH. Subarachnoid blood is associated with post-hemorrhagic ventricular dilatation and transient spinal subarachnoid cyst formation.

Intraoperative electroacupuncture relieves remifentanil-induced postoperative hyperalgesia via inhibiting spinal glial activation in rats

PubMed Central

Shi, Changxi; Liu, Yue; Zhang, Wei; Lei, Yishan; Lu, Cui’e; Sun, Rao; Sun, Yu’e; Jiang, Ming; Gu, Xiaoping; Ma, Zhengliang

2017-01-01

Background Accumulating studies have suggested that remifentanil, the widely-used opioid analgesic in clinical anesthesia, can activate the pronociceptive systems and enhance postoperative pain. Glial cells are thought to be implicated in remifentanil-induced hyperalgesia. Electroacupuncture is a complementary therapy to relieve various pain conditions with few side effects, and glial cells may be involved in its antinociceptive effect. In this study, we investigated whether intraoperative electroacupuncture could relieve remifentanil-induced postoperative hyperalgesia by inhibiting the activation of spinal glial cells, the production of spinal proinflammatory cytokines, and the activation of spinal mitogen-activated protein kinases. Methods A rat model of remifentanil-induced postoperative hyperalgesia was used in this study. Electroacupuncture during surgery was conducted at bilateral Zusanli (ST36) acupoints. Behavior tests, including mechanical allodynia and thermal hyperalgesia, were performed at different time points. Astrocytic marker glial fibrillary acidic protein, microglial marker Iba1, proinflammatory cytokines, and phosphorylated mitogen-activated protein kinases in the spinal cord were detected by Western blot and/or immunofluorescence. Results Mechanical allodynia and thermal hyperalgesia were induced by both surgical incision and remifentanil infusion, and remifentanil infusion significantly exaggerated and prolonged incision-induced pronociceptive effects. Glial fibrillary acidic protein, Iba1, proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α), and phosphorylated mitogen-activated protein kinases (p-p38, p-JNK, and p-ERK1/2) were upregulated after surgical incision, remifentanil infusion, and especially after their combination. Intraoperative electroacupuncture significantly attenuated incision- and/or remifentanil-induced pronociceptive effects, spinal glial activation, proinflammatory cytokine upregulation, and phosphorylated mitogen-activated protein kinase upregulation. Conclusions Our study suggests that remifentanil-induced postoperative hyperalgesia can be relieved by intraoperative electroacupuncture via inhibiting the activation of spinal glial cells, the upregulation of spinal proinflammatory cytokines, and the activation of spinal mitogen-activated protein kinases. PMID:28825338

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

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.

Neuromuscular Junction Formation between Human Stem cell-derived Motoneurons and Human Skeletal Muscle in a Defined System

PubMed Central

Guo, Xiufang; Gonzalez, Mercedes; Stancescu, Maria; Vandenburgh, Herman; Hickman, James

2011-01-01

Functional in vitro models composed of human cells will constitute an important platform in the next generation of system biology and drug discovery. This study reports a novel human-based in vitro Neuromuscular Junction (NMJ) system developed in a defined serum-free medium and on a patternable non-biological surface. The motoneurons and skeletal muscles were derived from fetal spinal stem cells and skeletal muscle stem cells. The motoneurons and skeletal myotubes were completely differentiated in the co-culture based on morphological analysis and electrophysiology. NMJ formation was demonstrated by phase contrast microscopy, immunocytochemistry and the observation of motoneuron-induced muscle contractions utilizing time lapse recordings and their subsequent quenching by D-Tubocurarine. Generally, functional human based systems would eliminate the issue of species variability during the drug development process and its derivation from stem cells bypasses the restrictions inherent with utilization of primary human tissue. This defined human-based NMJ system is one of the first steps in creating functional in vitro systems and will play an important role in understanding NMJ development, in developing high information content drug screens and as test beds in preclinical studies for spinal or muscular diseases/injuries such as muscular dystrophy, Amyotrophic lateral sclerosis and spinal cord repair. PMID:21944471

Neuromuscular junction formation between human stem cell-derived motoneurons and human skeletal muscle in a defined system.

PubMed

Guo, Xiufang; Gonzalez, Mercedes; Stancescu, Maria; Vandenburgh, Herman H; Hickman, James J

2011-12-01

Functional in vitro models composed of human cells will constitute an important platform in the next generation of system biology and drug discovery. This study reports a novel human-based in vitro Neuromuscular Junction (NMJ) system developed in a defined serum-free medium and on a patternable non-biological surface. The motoneurons and skeletal muscles were derived from fetal spinal stem cells and skeletal muscle stem cells. The motoneurons and skeletal myotubes were completely differentiated in the co-culture based on morphological analysis and electrophysiology. NMJ formation was demonstrated by phase contrast microscopy, immunocytochemistry and the observation of motoneuron-induced muscle contractions utilizing time-lapse recordings and their subsequent quenching by d-Tubocurarine. Generally, functional human based systems would eliminate the issue of species variability during the drug development process and its derivation from stem cells bypasses the restrictions inherent with utilization of primary human tissue. This defined human-based NMJ system is one of the first steps in creating functional in vitro systems and will play an important role in understanding NMJ development, in developing high information content drug screens and as test beds in preclinical studies for spinal or muscular diseases/injuries such as muscular dystrophy, Amyotrophic lateral sclerosis and spinal cord repair. Copyright © 2011 Elsevier Ltd. All rights reserved.

Problems of long-term spinal opioid treatment in advanced cancer patients.

PubMed

Mercadante, S

1999-01-01

Epidural and intrathecal techniques are well established techniques in cancer pain. However, several questions remain unresolved. The several problems of long-term spinal opioid treatment in advance cancer patients were reviewed. Indications for the use of spinal opioids include patients treated by systemic opioids with effective pain relief but with unacceptable side effects, or unsuccessful treatment with sequential strong opioid drug trials despite escalating doses. Therefore, the previous aggressive treatment with systemic opioids would leave as failures patients with difficult pain syndromes unresponsive to opioids. The choice of external or totally implanted delivery systems is based on different clinical considerations. The use of externalized tunneled intrathecal catheters has not been associated with higher rates of complications and is easier to place and use at home in debilitated patients late in the course of their disease. The intrathecal administration has a lower incidence of catheter occlusion, lower malfunctioning rate, lower dose requirement, and more effective pain control. Due to the lower daily doses and volumes, intrathecal treatment proved to be more suitable for treatment at home by a continuous infusion than the epidural treatment. Advantages of infusion techniques are more evident when using local anesthetics, since intermittent administration of bupivacaine often results in motor paralysis and hemodynamic instability. Morphine is the opioid of choice. An epidural dose of 10% of the systemic dose is often used. However, intrathecal administration of opioids and bupivacaine may substantially improve pain relief in patients unresponsive to high epidural doses of these drugs, Bupivacaine-induced adverse effects, including sensory deficits, motor complaints, signs of autonomic dysfunction or neurotoxicity have been reported to not occur with bupivacaine doses less than 30-60 mg/day. Adjuvant drugs may further improve analgesia. Different ranges of technical complication rates have been reported in the literature, most of them being associated with epidural catheters. Subcutaneous tunneling and fixation of the catheter, bacterial filters, minimum changes of tubings, careful exit site care weekly, site protection and monitoring of any sign of infection to prevent infection, and training for family under supervision, are recommended. Areas for additional research include the use of spinal adjuvants, the ideal spinal morphine-bupivacaine ratio. methods to improve spinal opioid responsiveness and long-term catheter management with appropriate home care programs.

Mechanical behavior of a novel non-fusion scoliosis correction device.

PubMed

Wessels, M; Hekman, E E G; Verkerke, G J

2013-11-01

We developed an innovative non-fusion correction system (XS LATOR) consisting of two individual implants that are extendable and extremely flexible. One implant, the XS LAT, generates a lateral, bending moment and one implant, the XS TOR, generates a torsion moment. Two 'inverse' implants were developed for generating torsion and lateral bending in a porcine model was tested for force delivery. An in vitro experiment was set up to describe the mechanical behavior of both implants. Narrow and wide ('inverse') versions of the XS TOR and XS LAT were mounted on an apparatus that was able to simulate different spinal geometries. The implants were anchored to three artificial vertebrae with integrated 6D force sensors, after which the vertebrae were rotated and translated towards the demanded position. The reaction forces and moments were recorded in all configurations. The maximal (lateral) bending moment, which occurred at the middle vertebra, was determined and, similarly, torque applied at the center of rotation of the middle vertebra was calculated. As expected, the wide and the small versions of the XS TOR generate a torque that increases during the growth of the system. Similarly, the XS LAT generates a bending moment that slightly increases during the growth of the system. The produced moments approximate the theoretically predicted ones. The contribution to the spinal stiffness ranges between 0.01Nm/° and 0.04Nm/° in bending and between 0.03Nm/° and 0.08Nm/° in torsion. The XS TOR and the XS LAT are able to generate a torque and a bending moment that remain (fairly) constant during spinal growth when a shape change due to the generated moment/torque is achieved. The stiffness of the implants is extremely low, being only a fraction of the stiffness of conventional, spinal fusion constructs. Current fusion systems, such as non-segmental spinal constructs generally, have 11 times higher stiffness in torsion and 6 times higher stiffness in lateral bending. Implantation of the XS LATOR adds 9% stiffness in axial rotation and 17% stiffness in lateral bending (to the original spinal stiffness). By preserving the flexibility of the spine after implantation, fusion of the vertebrae in the instrumented region is likely to be prevented. © 2013 Elsevier Ltd. All rights reserved.

Extraosseous, epidural cavernous hemangioma with back pain.

PubMed

Ozkal, Birol; Yaldiz, Can; Yaman, Onur; Ozdemır, Nail; Dalbayrak, Sedat

2015-01-01

Cavernous malformations are characterized by enlarged vascular structures located in benign neural tissues within the cerebellum and spinal cord of the central nervous system. Cavernous hemangiomas (CHs) account for 5% to 12% of all spinal vascular malformations. We removed a hemorrhagic thoracic mass in a 40-year-old male patient who presented with progressive neurological deficits. We found it appropriate to present this case due to its rarity.

Clitoral Sexual Arousal: Neuronal Tracing Study From the Clitoris Through the Spinal Tracts

PubMed Central

Martin-Alguacil, Nieves; Schober, Justine M.; Sengelaub, Dale R.; Pfaff, Donald W.; Shelley, Deborah N.

2009-01-01

Purpose Although genital tactile stimulation is regarded as a precursor to sexual arousal and a recognized initiator of central nervous system arousal, specific afferent neural pathways transmit sensory stimuli of arousal, beginning at the epithelial level on the clitoris and following the course of arousal stimuli through the central nervous system. Limited knowledge exists of the pathway from the cutaneous receptors of nerves originating in the epithelial tissue of the clitoris and continuing to spinal cord afferents. Such information may contribute to an understanding of sexual arousal, particularly in female vertebrates. We further defined the neural pathways and mechanisms responsible for arousal originating in the epithelium of the clitoris as well as related neural pathways to the spinal cord in a murine model. Materials and Methods We performed a comprehensive review of the published relevant clinical and histological material from human and nonhuman vertebrate studies. In 29 adult female C57B1/6 mice the distribution of pelvic nerves and vessels was mapped. Gross dissection of 4 female mice was facilitated by resin injection of the vascular system in 2. Neuronal tracing was performed in 25 mice that received clitoral injection of wheat germ agglutinin-horseradish peroxidase into the clitoris and were sacrificed after 72 to 96 hours. The spinal cord and periclitoral tissue were removed and fixed. Immunohistochemistry was performed. Results Gross anatomy of the mouse clitoris showed that pudendal and hypogastric nerves have a major role in the innervation of the external genitalia. Neuronal tracing revealed that the greatest nerve density was noted in the L5/6 spinal cord. The distribution extended from S1 to L2 with no labeling seen in the L3 spinal cord. Wheat germ agglutinin-horseradish peroxidase labeling was seen caudal in levels S1 through L4 and rostral in L2. Conclusions Understanding the neuroanatomy of the clitoris using a murine model may provide a valuable tool for the study of sexual arousal disorders and the further understanding of sexual function related to neural pathologies and trauma. PMID:18707740

Predictive value of seven preoperative prognostic scoring systems for spinal metastases

PubMed Central

Leithner, Andreas; Radl, Roman; Gruber, Gerald; Hochegger, Markus; Leithner, Katharina; Welkerling, Heike; Rehak, Peter

2008-01-01

Predicting prognosis is the key factor in selecting the proper treatment modality for patients with spinal metastases. Therefore, various assessment systems have been designed in order to provide a basis for deciding the course of treatment. Such systems have been proposed by Tokuhashi, Sioutos, Tomita, Van der Linden, and Bauer. The scores differ greatly in the kind of parameters assessed. The aim of this study was to evaluate the prognostic value of each score. Eight parameters were assessed for 69 patients (37 male, 32 female): location, general condition, number of extraspinal bone metastases, number of spinal metastases, visceral metastases, primary tumour, severity of spinal cord palsy, and pathological fracture. Scores according to Tokuhashi (original and revised), Sioutos, Tomita, Van der Linden, and Bauer were assessed as well as a modified Bauer score without scoring for pathologic fracture. Nineteen patients were still alive as of September 2006 with a minimum follow-up of 12 months. All other patients died after a mean period of 17 months after operation. The mean overall survival period was only 3 months for lung cancer, followed by prostate (7 months), kidney (23 months), breast (35 months), and multiple myeloma (51 months). At univariate survival analysis, primary tumour and visceral metastases were significant parameters, while Karnofsky score was only significant in the group including myeloma patients. In multivariate analysis of all seven parameters assessed, primary tumour and visceral metastases were the only significant parameters. Of all seven scoring systems, the original Bauer score and a Bauer score without scoring for pathologic fracture had the best association with survival (P < 0.001). The data of the present study emphasize that the original Bauer score and a modified Bauer score without scoring for pathologic fracture seem to be practicable and highly predictive preoperative scoring systems for patients with spinal metastases. However, decision for or against surgery should never be based alone on a prognostic score but should take symptoms like pain or neurological compromise into account. PMID:18787846

Perspective of Value-Based Management of Spinal Disorders in Brazil.

PubMed

Teles, Alisson R; Righesso, Orlando; Gullo, Maria Carolina R; Ghogawala, Zoher; Falavigna, Asdrubal

2016-03-01

The state of value-based management of spinal disorders and ongoing Brazilian strategies toward its implementation are highlighted in this article. The health care system, economic impact of spine surgery, use of patient-reported outcomes, ongoing studies about health economics, and current strategies toward implementation of quality assessment of spine care in Brazil are reviewed. During the past 20 years, there has been an increase of 226% in the number and 540% in the total cost of spine surgeries in the public health system. Examples of economic regulatory mechanisms involve the process of health technology assessment and the auditing processes imposed by health insurance companies. Some barriers to implementing clinical registries were identified from a large Latin American survey. Strategies based on education and technical support have been conducted to improve the quality of comparative-effectiveness research in spine care. Only 1 cost-utility study on spine care has been published until now. The paradigm of value-based management of spinal disorders is still incipient in Brazil. Some issues from our analysis must be emphasized: (1) Brazil presents many regional disparities and scarce resources for health care; it is crucial for the health system to allocate resources based on the value of interventions; (2) because of the high economic and social burden of developing new technologies for diagnosis and treatment, research in health economics of spine care in Brazil should be prioritized; (3) these efforts would help to provide a more accessible and effective health system for patients with spinal problems. Copyright © 2016 Elsevier Inc. All rights reserved.

Human spinal locomotor control is based on flexibly organized burst generators.

PubMed

Danner, Simon M; Hofstoetter, Ursula S; Freundl, Brigitta; Binder, Heinrich; Mayr, Winfried; Rattay, Frank; Minassian, Karen

2015-03-01

Constant drive provided to the human lumbar spinal cord by epidural electrical stimulation can cause local neural circuits to generate rhythmic motor outputs to lower limb muscles in people paralysed by spinal cord injury. Epidural spinal cord stimulation thus allows the study of spinal rhythm and pattern generating circuits without their configuration by volitional motor tasks or task-specific peripheral feedback. To reveal spinal locomotor control principles, we studied the repertoire of rhythmic patterns that can be generated by the functionally isolated human lumbar spinal cord, detected as electromyographic activity from the legs, and investigated basic temporal components shared across these patterns. Ten subjects with chronic, motor-complete spinal cord injury were studied. Surface electromyographic responses to lumbar spinal cord stimulation were collected from quadriceps, hamstrings, tibialis anterior, and triceps surae in the supine position. From these data, 10-s segments of rhythmic activity present in the four muscle groups of one limb were extracted. Such samples were found in seven subjects. Physiologically adequate cycle durations and relative extension- and flexion-phase durations similar to those needed for locomotion were generated. The multi-muscle activation patterns exhibited a variety of coactivation, mixed-synergy and locomotor-like configurations. Statistical decomposition of the electromyographic data across subjects, muscles and samples of rhythmic patterns identified three common temporal components, i.e. basic or shared activation patterns. Two of these basic patterns controlled muscles to contract either synchronously or alternatingly during extension- and flexion-like phases. The third basic pattern contributed to the observed muscle activities independently from these extensor- and flexor-related basic patterns. Each bifunctional muscle group was able to express both extensor- and flexor-patterns, with variable ratios across the samples of rhythmic patterns. The basic activation patterns can be interpreted as central drives implemented by spinal burst generators that impose specific spatiotemporally organized activation on the lumbosacral motor neuron pools. Our data thus imply that the human lumbar spinal cord circuits can form burst-generating elements that flexibly combine to obtain a wide range of locomotor outputs from a constant, repetitive input. It may be possible to use this flexibility to incorporate specific adaptations to gait and stance to improve locomotor control, even after severe central nervous system damage. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Human spinal locomotor control is based on flexibly organized burst generators

PubMed Central

Danner, Simon M.; Hofstoetter, Ursula S.; Freundl, Brigitta; Binder, Heinrich; Mayr, Winfried; Rattay, Frank

2015-01-01

Constant drive provided to the human lumbar spinal cord by epidural electrical stimulation can cause local neural circuits to generate rhythmic motor outputs to lower limb muscles in people paralysed by spinal cord injury. Epidural spinal cord stimulation thus allows the study of spinal rhythm and pattern generating circuits without their configuration by volitional motor tasks or task-specific peripheral feedback. To reveal spinal locomotor control principles, we studied the repertoire of rhythmic patterns that can be generated by the functionally isolated human lumbar spinal cord, detected as electromyographic activity from the legs, and investigated basic temporal components shared across these patterns. Ten subjects with chronic, motor-complete spinal cord injury were studied. Surface electromyographic responses to lumbar spinal cord stimulation were collected from quadriceps, hamstrings, tibialis anterior, and triceps surae in the supine position. From these data, 10-s segments of rhythmic activity present in the four muscle groups of one limb were extracted. Such samples were found in seven subjects. Physiologically adequate cycle durations and relative extension- and flexion-phase durations similar to those needed for locomotion were generated. The multi-muscle activation patterns exhibited a variety of coactivation, mixed-synergy and locomotor-like configurations. Statistical decomposition of the electromyographic data across subjects, muscles and samples of rhythmic patterns identified three common temporal components, i.e. basic or shared activation patterns. Two of these basic patterns controlled muscles to contract either synchronously or alternatingly during extension- and flexion-like phases. The third basic pattern contributed to the observed muscle activities independently from these extensor- and flexor-related basic patterns. Each bifunctional muscle group was able to express both extensor- and flexor-patterns, with variable ratios across the samples of rhythmic patterns. The basic activation patterns can be interpreted as central drives implemented by spinal burst generators that impose specific spatiotemporally organized activation on the lumbosacral motor neuron pools. Our data thus imply that the human lumbar spinal cord circuits can form burst-generating elements that flexibly combine to obtain a wide range of locomotor outputs from a constant, repetitive input. It may be possible to use this flexibility to incorporate specific adaptations to gait and stance to improve locomotor control, even after severe central nervous system damage. PMID:25582580

Investigation of spinal cerebrospinal fluid-contacting neurons expressing PKD2L1: evidence for a conserved system from fish to primates

PubMed Central

Djenoune, Lydia; Khabou, Hanen; Joubert, Fanny; Quan, Feng B.; Nunes Figueiredo, Sophie; Bodineau, Laurence; Del Bene, Filippo; Burcklé, Céline; Tostivint, Hervé; Wyart, Claire

2014-01-01

Over 90 years ago, Kolmer and Agduhr identified spinal cerebrospinal fluid-contacting neurons (CSF-cNs) based on their morphology and location within the spinal cord. In more than 200 vertebrate species, they observed ciliated neurons around the central canal that extended a brush of microvilli into the cerebrospinal fluid (CSF). Although their morphology is suggestive of a primitive sensory cell, their function within the vertebrate spinal cord remains unknown. The identification of specific molecular markers for these neurons in vertebrates would benefit the investigation of their physiological roles. PKD2L1, a transient receptor potential channel that could play a role as a sensory receptor, has been found in cells contacting the central canal in mouse. In this study, we demonstrate that PKD2L1 is a specific marker for CSF-cNs in the spinal cord of mouse (Mus musculus), macaque (Macaca fascicularis) and zebrafish (Danio rerio). In these species, the somata of spinal PKD2L1+ CSF-cNs were located below or within the ependymal layer and extended an apical bulbous extension into the central canal. We found GABAergic PKD2L1-expressing CSF-cNs in all three species. We took advantage of the zebrafish embryo for its transparency and rapid development to identify the progenitor domains from which pkd2l1+ CSF-cNs originate. pkd2l1+ CSF-cNs were all GABAergic and organized in two rows—one ventral and one dorsal to the central canal. Their location and marker expression is consistent with previously described Kolmer–Agduhr cells. Accordingly, pkd2l1+ CSF-cNs were derived from the progenitor domains p3 and pMN defined by the expression of nkx2.2a and olig2 transcription factors, respectively. Altogether our results suggest that a system of CSF-cNs expressing the PKD2L1 channel is conserved in the spinal cord across bony vertebrate species. PMID:24834029

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.

Immunohistochemical localization of urotensin I/corticotropin-releasing factor, urotensin II, and serotonin immunoreactivities in the caudal spinal cord of nonteleost fishes.

PubMed

Onstott, D; Elde, R

1986-07-08

Neurosecretory cells in the caudal spinal cord of fishes were first discovered in elasmobranches. However, most of the subsequent work on the caudal neurosecretory system has emphasized its morphology and function in teleosts. Two major peptides, urotensins I and II (UI and UII), have been isolated from this system in teleosts and their amino acid sequences have been determined. We have used immunohistochemical techniques to confirm and expand previous morphological and pharmacological findings regarding the phylogenetic occurrence and the anatomical organization of the caudal neurosecretory system and to localize putative neurohormonal products within its structural elements. UII-immunoreactive neuronal structures were found in the holocephalan, Hydrolagus collei; the elasmobranches, Squalus acanthias, Dasyatis sabina, and Raja binoculata; the dipnoan, Protopterus annectens; the brachiopterygian, Erpetoichthys calabaricus; the chondrostean, Polyodon spathula; and the holosteans Lepisosteus platyrhinchus and Amia calva. UI/corticotropin-releasing-factor immunoreactive elements were detected in the caudal spinal cords of Petromyzon marinus, Raja binoculata, Polydon spathula, Lepisosteus platyrhinchus, L. osseus, L. platostomus, and Amia calva. In addition, in several of these species, immunohistochemical techniques have provided evidence for serotoninergic input to the caudal neurosecretory system.

A 51-year-old man with intramedullary spinal cord abscess having a patent foramen ovale

PubMed Central

Higuchi, Kanako; Ishihara, Hiroyuki; Okuda, Shiho; Kanda, Fumio

2011-01-01

The authors report a case of a 51-year-old man with intramedullary spinal cord abscess (ISCA) having a patent foramen ovale (PFO). He developed fever and tetraplegia after a recent dental treatment. MRI showed ISCA with longitudinal swelling from the upper cervical to the lumbar spinal cord. Cerebrospinal fluid (CSF) analysis indicated bacterial meningitis, and the culture of CSF revealed Streptococcus viridans. Transoesophageal echocardiography revealed the existence of a PFO. We suspected another possibility other than systemic bacteraemia, that paradoxical bacteric embolisation through PFO after the dental treatment caused ISCA. While several reports of brain abscess with PFO are available, this is the first report of ISCA with PFO. PMID:22696715

Safe performance of spinal anesthesia in a critical patient with neurofibromatosis, pectus carinatum, and temporomandibular joint dysfunction: A case report.

PubMed

Zencirci, Beyazit

2010-05-03

Neurofibromatosis is a syndrome caused by the abnormal deposition of neural tissues of the nervous system, endocrine system, visceral structures, and skin. On the other hand, pectus carinatum and temporomandibular joint dysfunction are illnesses that adversly affect the respiratory system and cause additional problems in airway management. Fifty-eight-year-old Turkish male patient had neurofibromatosis, pectus carinatum and temporomandibular joint dysfunction. The case was due to be operated on with the diagnosis of incarcerated umbilical hernia. Spinal anesthesia was successfully performed and the duration of the surgery was 1 hour. No postoperative complications were observed and he was discharged from the hospital on the 3rd post-operative day. The anesthetic management of patients with neurofibromatosis requires attention to all possible abnormalities and associated disturbances. Furthermore, the presence of pectus carinatum and temporomandibular joint dysfunction also increase the potential risks. The operation was successfully completed with spinal anesthesia that was carefully applied upon taking the required measures and considering all pathologies that may accompany the case and complications that may occur.

Safe performance of spinal anesthesia in a critical patient with neurofibromatosis, pectus carinatum, and temporomandibular joint dysfunction: A case report

PubMed Central

2010-01-01

Background Neurofibromatosis is a syndrome caused by the abnormal deposition of neural tissues of the nervous system, endocrine system, visceral structures, and skin. On the other hand, pectus carinatum and temporomandibular joint dysfunction are illnesses that adversly affect the respiratory system and cause additional problems in airway management. Case Presentation Fifty-eight-year-old Turkish male patient had neurofibromatosis, pectus carinatum and temporomandibular joint dysfunction. The case was due to be operated on with the diagnosis of incarcerated umbilical hernia. Spinal anesthesia was successfully performed and the duration of the surgery was 1 hour. No postoperative complications were observed and he was discharged from the hospital on the 3rd post-operative day. Conclusion The anesthetic management of patients with neurofibromatosis requires attention to all possible abnormalities and associated disturbances. Furthermore, the presence of pectus carinatum and temporomandibular joint dysfunction also increase the potential risks. The operation was successfully completed with spinal anesthesia that was carefully applied upon taking the required measures and considering all pathologies that may accompany the case and complications that may occur. PMID:20438631

Murine neural crest stem cells and embryonic stem cell-derived neuron precursors survive and differentiate after transplantation in a model of dorsal root avulsion.

PubMed

Konig, Niclas; Trolle, Carl; Kapuralin, Katarina; Adameyko, Igor; Mitrecic, Dinko; Aldskogius, Hakan; Shortland, Peter J; Kozlova, Elena N

2017-01-01

Spinal root avulsion results in paralysis and sensory loss, and is commonly associated with chronic pain. In addition to the failure of avulsed dorsal root axons to regenerate into the spinal cord, avulsion injury leads to extensive neuroinflammation and degeneration of second-order neurons in the dorsal horn. The ultimate objective in the treatment of this condition is to counteract degeneration of spinal cord neurons and to achieve functionally useful regeneration/reconnection of sensory neurons with spinal cord neurons. Here we compare survival and migration of murine boundary cap neural crest stem cells (bNCSCs) and embryonic stem cells (ESCs)-derived, predifferentiated neuron precursors after their implantation acutely at the junction between avulsed dorsal roots L3-L6 and the spinal cord. Both types of cells survived transplantation, but showed distinctly different modes of migration. Thus, bNCSCs migrated into the spinal cord, expressed glial markers and formed elongated tubes in the peripheral nervous system (PNS) compartment of the avulsed dorsal root transitional zone (DRTZ) area. In contrast, the ESC transplants remained at the site of implantation and differentiated to motor neurons and interneurons. These data show that both stem cell types successfully survived implantation to the acutely injured spinal cord and maintained their differentiation and migration potential. These data suggest that, depending on the source of neural stem cells, they can play different beneficial roles for recovery after dorsal root avulsion. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Proinflammatory cytokines oppose opioid induced acute and chronic analgesia

PubMed Central

Hutchinson, Mark R.; Coats, Benjamen D.; Lewis, Susannah S.; Zhang, Yingning; Sprunger, David B.; Rezvani, Niloofar; Baker, Eric M.; Jekich, Brian M.; Wieseler, Julie L.; Somogyi, Andrew A.; Martin, David; Poole, Stephen; Judd, Charles M.; Maier, Steven F.; Watkins, Linda R.

2008-01-01

Spinal proinflammatory cytokines are powerful pain-enhancing signals that contribute to pain following peripheral nerve injury (neuropathic pain). Recently, one proinflammatory cytokine, interleukin-1, was also implicated in the loss of analgesia upon repeated morphine exposure (tolerance). In contrast to prior literature, we demonstrate that the action of several spinal proinflammatory cytokines oppose systemic and intrathecal opioid analgesia, causing reduced pain suppression. In vitro morphine exposure of lumbar dorsal spinal cord caused significant increases in proinflammatory cytokine and chemokine release. Opposition of analgesia by proinflammatory cytokines is rapid, occurring ≤5 minutes after intrathecal (perispinal) opioid administration. We document that opposition of analgesia by proinflammatory cytokines cannot be accounted for by an alteration in spinal morphine concentrations. The acute anti-analgesic effects of proinflammatory cytokines occur in a p38 mitogen-activated protein kinase and nitric oxide dependent fashion. Chronic intrathecal morphine or methadone significantly increased spinal glial activation (toll-like receptor 4 mRNA and protein) and the expression of multiple chemokines and cytokines, combined with development of analgesic tolerance and pain enhancement (hyperalgesia, allodynia). Statistical analysis demonstrated that a cluster of cytokines and chemokines was linked with pain-related behavioral changes. Moreover, blockade of spinal proinflammatory cytokines during a stringent morphine regimen previously associated with altered neuronal function also attenuated enhanced pain, supportive that proinflammatory cytokines are importantly involved in tolerance induced by such regimens. These data implicate multiple opioid-induced spinal proinflammatory cytokines in opposing both acute and chronic opioid analgesia, and provide a novel mechanism for the opposition of acute opioid analgesia. PMID:18599265

Chondroitin sulfates do not impede axonal regeneration in goldfish spinal cord.

PubMed

Takeda, Akihito; Okada, Soichiro; Funakoshi, Kengo

2017-10-15

Chondroitin sulfate proteoglycans produced in glial scar tissue are a major inhibitory factor for axonal regeneration after central nervous system injury in mammals. The inhibition is largely due to chondroitin sulfates, whose effects differ according to the sulfation pattern. In contrast to mammals, fish nerves spontaneously regenerate beyond the scar tissue after spinal cord injury, although the mechanisms that allow for axons to pass through the scar are unclear. Here, we used immunohistochemistry to examine the expression of two chondroitin sulfates with different sulfation variants at the lesion site in goldfish spinal cord. The intact spinal cord was immunoreactive for both chondroitin sulfate-A (CS-A) and chondroitin sulfate-C (CS-C), and CS-A immunoreactivity overlapped extensively with glial processes positive for glial fibrillary acidic protein. At 1week after inducing the spinal lesion, CS-A immunoreactivity was observed in the cell bodies and extracellular matrix, as well as in glial processes surrounding the lesion center. At 2weeks after the spinal lesion, regenerating axons entering the lesion center overtook the CS-A abundant area. In contrast, at 1week after lesion induction, CS-C immunoreactivity was significantly decreased, and at 2weeks after lesion induction, CS-C immunoreactivity was observed along the regenerating axons entering the lesion center. The present findings suggest that after spinal cord injury in goldfish, chondroitin sulfate proteoglycans are deposited in the extracellular matrix at the lesion site but do not form an impenetrable barrier to the growth of regenerating axons. Copyright © 2017 Elsevier B.V. All rights reserved.

The plasticity of descending controls in pain: translational probing.

PubMed

Bannister, Kirsty; Dickenson, A H

2017-07-01

Descending controls, comprising pathways that originate in midbrain and brainstem regions and project onto the spinal cord, have long been recognised as key links in the multiple neural networks that interact to produce the overall pain experience. There is clear evidence from preclinical and clinical studies that both peripheral and central sensitisation play important roles in determining the level of pain perceived. Much emphasis has been put on spinal cord mechanisms in central excitability, but it is now becoming clear that spinal hyperexcitability can be regulated by descending pathways from the brain that originate from predominantly noradrenergic and serotonergic systems. One pain can inhibit another. In this respect diffuse noxious inhibitory controls (DNIC) are a unique form of endogenous descending inhibitory pathway since they can be easily evoked and quantified in animals and man. The spinal pharmacology of pathways that subserve DNIC are complicated; in the normal situation these descending controls produce a final inhibitory effect through the actions of noradrenaline at spinal α 2 -adrenoceptors, although serotonin, acting on facilitatory spinal 5-HT 3 receptors, influences the final expression of DNIC also. These descending pathways are altered in neuropathy and the effects of excess serotonin may now become inhibitory through activation of spinal 5-HT 7 receptors. Conditioned pain modulation (CPM) is the human counterpart of DNIC and requires a descending control also. Back and forward translational studies between DNIC and CPM, gauged between bench and bedside, are key for the development of analgesic therapies that exploit descending noradrenergic and serotonergic control pathways. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Combined spinal epidural anesthesia for laparoscopic appendectomy in adults: A case series

PubMed Central

Mane, Rajesh S.; Patil, Manjunath C.; Kedareshvara, K. S.; Sanikop, C. S.

2012-01-01

Background: Laparoscopy is one of the most common surgical procedures and is the procedure of choice for most of the elective abdominal surgeries performed preferably under endotracheal general anesthesia. Technical advances in the field of laparoscopy have helped to reduce surgical trauma and discomfort, reduce anesthetic requirement resulting in shortened hospital stay. Recently, regional anaesthetic techniques have been found beneficial, especially in patients at a high risk to receive general anesthesia. Herewith we present a case series of laparoscopic appendectomy in eight American Society of Anaesthesiologists (ASA) I and II patients performed under spinal-epidural anaesthesia. Methods: Eight ASA Grade I and II adult patients undergoing elective Laparoscopic appendectomy received Combined Spinal Epidural Anaesthesia. Spinal Anaesthesia was performed at L2-L3 interspace using 2 ml of 0.5% (10 mg) hyperbaric Bupivacaine mixed with 0.5ml (25 micrograms) of Fentanyl. Epidural catheter was inserted at T10-T11 interspace for inadequate spinal anaesthesia and postoperative pain relief. Perioperative events and operative difficulty were studied. Systemic drugs were administered if patients complained of shoulder pain, abdominal discomfort, nausea or hypotension. Results: Spinal anaesthesia was adequate for surgery with no operative difficulty in all the patients. Intraoperatively, two patients experienced right shoulder pain and received Fentanyl, one patient was given Midazolam for anxiety and two were given Ephedrine for hypotension. The postoperative period was uneventful. Conclusion: Spinal anaesthesia with Hyperbaric Bupivacaine and Fentanyl is adequate and safe for elective laparoscopic appendectomy in healthy patients but careful evaluation of the method is needed particularly in compromised cardio respiratory conditions. PMID:22412773

O-arm with navigation versus C-arm: a review of screw placement over 3 years at a major trauma center.

PubMed

Verma, S K; Singh, P K; Agrawal, D; Sinha, S; Gupta, D; Satyarthee, G D; Sharma, B S

2016-12-01

There is a relatively high incidence of screw misplacement during spinal instrumentation due to distortion of normal anatomy following spinal trauma. The O-arm is the next-generation spinal navigation tool that provides intraoperative 3-D imaging and navigation for spine surgeries. To evaluate and compare the use of O-arm as compared to C-arm for spinal trauma in a Level I trauma center in India. In this retrospective study over 3 years (July 2010-April 2013), All patients of spinal injury who underwent spinal instrumentation were divided into O-arm group and C-arm group. Accuracy of screw placement was assessed during each surgery in both groups. A total of 587 patients were evaluated during the study period. There were 278 patients in O-arm group and 309 patients in C-arm group. Both groups were well matched in mean age (27.7 vs. 28.9 years), ASIA grades, and level of injury. The number of screws placed was significantly higher in the C-arm group as compared to the O-arm group (2173 vs. 1720). However, the O-arm group had significantly less screw malplacement rate of 0.93% (n = 16) as compared to malplacement rate in C-arm group of 8.79% (n = 191, p < 0.05). Use of O-arm imaging system ensures accurate screw placement and dramatically decreases screw malplacement rate, thus providing better patient safety. Its use is especially beneficial in academic and teaching centers where novice surgeons can attain results equivalent to that of experts in spinal instrumentation.

[Neuronal control of posture and locomotion in decerebrated and spinalized animals].

PubMed

Musienko, P E; Gorskiĭ, O V; Kilimnik, V A; Kozlovskaia, I B; Courtine, G; Edgerton, V R; Gerasimenko, Iu P

2013-03-01

We have found that the brainstem-spinal cord circuitry of decerebrated cats actively maintain the equilibrium during standing, walking and imposed mechanical perturbations similar to that observed in intact animals. The corrective hindlimb motor responses during standing included redistribution of the extensor activity ipsilateral and contralateral to perturbation. The postural corrections in walking cats were due to considerable modification of EMG pattern in the limbs as well as changing of the swing-stance phases of the step cycle and ground reaction forces depending of perturbation side. Thus the basic mechanisms for balance control of decerebrated animals in these two forms of motor behavior are different. Balance-related adjustments relied entirely on the integration of somatosensory information arising from the moving hindquarters because of the suppression of vestibular, visual, and head-neck-trunk sensory input. We propose that the somatosensory input from the hindquarters in concert with the lumbosacral spinal circuitry can control the dynamics of the hindquarters sufficient to sustain balance. We found that, after isolation from the brainstem or forebrain, lumbosacral circuits receiving tonic epidural electrical stimulation can effectively control equilibrium during standing and stepping. Detailed analyses of the relationships among muscle activity, trunk kinematics, and limb kinetics indicate that spinal motor systems utilize a combination of feedback and feedforward strategies to maintain dynamic equilibrium during walking. The unexpected ability of spinal circuitries to exert efficient postural control in the presence of epidural electrical stimulation in decerebrated and spinal cats have significant implications for the potential of humans with a severe spinal cord injury to regain a significant level of functional standing and walking capacities.

Fertility and sexuality in the spinal cord injury patient.

PubMed

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

2018-06-14

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

Label-free imaging of rat spinal cords based on multiphoton microscopy

NASA Astrophysics Data System (ADS)

Liao, Chenxi; Wang, Zhenyu; Zhou, Linquan; Zhu, Xiaoqin; Liu, Wenge; Chen, Jianxin

2016-10-01

As an integral part of the central nervous system, the spinal cord is a communication cable between the body and the brain. It mainly contains neurons, glial cells, nerve fibers and fiber tracts. The recent development of the optical imaging technique allows high-resolution imaging of biological tissues with the great potential for non-invasively looking inside the body. In this work, we evaluate the imaging capacity of multiphoton microscopy (MPM) based on second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) for the cells and extracellular matrix in the spinal cord at molecular level. Rat spinal cord tissues were sectioned and imaged by MPM to demonstrate that MPM is able to show the microstructure including white matter, gray matter, ventral horns, dorsal horns, and axons based on the distinct intrinsic sources in each region of spinal cord. In the high-resolution and high-contrast MPM images, the cell profile can be clearly identified as dark shadows caused by nuclei and encircled by cytoplasm. The nerve fibers in white matter region emitted both SHG and TPEF signals. The multiphoton microscopic imaging technique proves to be a fast and effective tool for label-free imaging spinal cord tissues, based on endogenous signals in biological tissue. It has the potential to extend this optical technique to clinical study, where the rapid and damage-free imaging is needed.

Supraspinal control of spinal reflex responses to body bending during different behaviours in lampreys

PubMed Central

Hsu, Li‐Ju; Zelenin, Pavel V.; Orlovsky, Grigori N.

2016-01-01

Key points Spinal reflexes are substantial components of the motor control system in all vertebrates and centrally driven reflex modifications are essential to many behaviours, but little is known about the neuronal mechanisms underlying these modifications.To study this issue, we took advantage of an in vitro brainstem–spinal cord preparation of the lamprey (a lower vertebrate), in which spinal reflex responses to spinal cord bending (caused by signals from spinal stretch receptor neurons) can be evoked during different types of fictive behaviour.Our results demonstrate that reflexes observed during fast forward swimming are reversed during escape behaviours, with the reflex reversal presumably caused by supraspinal commands transmitted by a population of reticulospinal neurons.NMDA receptors are involved in the formation of these commands, which are addressed primarily to the ipsilateral spinal networks.In the present study the neuronal mechanisms underlying reflex reversal have been characterized for the first time. Abstract Spinal reflexes can be modified during different motor behaviours. However, our knowledge about the neuronal mechanisms underlying these modifications in vertebrates is scarce. In the lamprey, a lower vertebrate, body bending causes activation of intraspinal stretch receptor neurons (SRNs) resulting in spinal reflexes: activation of motoneurons (MNs) with bending towards either the contralateral or ipsilateral side (a convex or concave response, respectively). The present study had two main aims: (i) to investigate how these spinal reflexes are modified during different motor behaviours, and (ii) to reveal reticulospinal neurons (RSNs) transmitting commands for the reflex modification. For this purpose in in vitro brainstem–spinal cord preparation, RSNs and reflex responses to bending were recorded during different fictive behaviours evoked by supraspinal commands. We found that during fast forward swimming MNs exhibited convex responses. By contrast, during escape behaviours, MNs exhibited concave responses. We found RSNs that were activated during both stimulation causing reflex reversal without initiation of any specific behaviour, and stimulation causing reflex reversal during escape behaviour. We suggest that these RSNs transmit commands for the reflex modification. Application of the NMDA antagonist (AP‐5) to the brainstem significantly decreased the reversed reflex, suggesting involvement of NMDA receptors in the formation of these commands. Longitudinal split of the spinal cord did not abolish the reflex reversal caused by supraspinal commands, suggesting an important role for ipsilateral networks in determining this type of motor response. This is the first study to reveal the neuronal mechanisms underlying supraspinal control of reflex reversal. PMID:27589479

AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)

ClinicalTrials.gov

2018-05-21

Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Nervous System Diseases; Central Nervous System Diseases

Effect of prenatal and early life paracetamol exposure on the level of neurotransmitters in rats--Focus on the spinal cord.

PubMed

Blecharz-Klin, Kamilla; Joniec-Maciejak, Ilona; Jawna, Katarzyna; Pyrzanowska, Justyna; Piechal, Agnieszka; Wawer, Adriana; Widy-Tyszkiewicz, Ewa

2015-12-01

The present study has examined the influence of the prenatal and early life administration of paracetamol on the level of neurotransmitters in the spinal cord of rat pups. The effect of the drug was evaluated in 2-month old Wistar male rats exposed to paracetamol in doses of 5 (P5, n=9) or 15 mg/kg (P15, n=9) p.o. during the prenatal period and after birth until the completion of the second month of life. A parallel control group received tap water (Con, n=9). In this study we have determined the level of monoamines, their metabolites and amino acids in the spinal cord of rats using high performance liquid chromatography (HPLC) in the second month of life. The present experiment demonstrates the action of paracetamol at the molecular level associated with significant modulation of neurotransmission in the spinal cord related to dopaminergic and noradrenergic systems. Simultaneously, paracetamol administration increases the content of an aspartic and glutamic acids in the spinal cord at a critical time during development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Propitious Therapeutic Modulators to Prevent Blood-Spinal Cord Barrier Disruption in Spinal Cord Injury.

PubMed

Kumar, Hemant; Ropper, Alexander E; Lee, Soo-Hong; Han, Inbo

2017-07-01

The blood-spinal cord barrier (BSCB) is a specialized protective barrier that regulates the movement of molecules between blood vessels and the spinal cord parenchyma. Analogous to the blood-brain barrier (BBB), the BSCB plays a crucial role in maintaining the homeostasis and internal environmental stability of the central nervous system (CNS). After spinal cord injury (SCI), BSCB disruption leads to inflammatory cell invasion such as neutrophils and macrophages, contributing to permanent neurological disability. In this review, we focus on the major proteins mediating the BSCB disruption or BSCB repair after SCI. This review is composed of three parts. Section 1. SCI and the BSCB of the review describes critical events involved in the pathophysiology of SCI and their correlation with BSCB integrity/disruption. Section 2. Major proteins involved in BSCB disruption in SCI focuses on the actions of matrix metalloproteinases (MMPs), tumor necrosis factor alpha (TNF-α), heme oxygenase-1 (HO-1), angiopoietins (Angs), bradykinin, nitric oxide (NO), and endothelins (ETs) in BSCB disruption and repair. Section 3. Therapeutic approaches discusses the major therapeutic compounds utilized to date for the prevention of BSCB disruption in animal model of SCI through modulation of several proteins.

Effects of intrathecal ketorolac on human experimental pain

PubMed Central

Eisenach, James C.; Curry, Regina; Tong, Chuanyao; Houle, Timothy T.; Yaksh, Tony L.

2010-01-01

Background Nonsteroidal antiinflammatory drugs, the most commonly used analgesics, reduce pain by inhibiting cyclooxygenase at peripheral sites of inflammation, but potentially also by inhibiting cyclooxygenase in the central nervous system, especially the spinal cord. Animal studies suggest that products of cyclooxygenase in the spinal cord do not alter pain responses to acute noxious stimuli, but reduce pain and sensitization following peripheral inflammation. We used spinal injection of small doses of the cyclooxygenase inhibitor, ketorolac, to survey the role of spinal cyclooxygenase in human experimental pain and hypersensitivity states. Methods Following regulatory agency approval and informed consent, we examined the effect of 2.0 mg intrathecal ketorolac in 41 healthy volunteers to acute noxious thermal stimuli in normal skin and to mechanical stimuli in skin sensitized by topical capsaicin or ultraviolet burn. We also examined the effect of intravenous ketorolac, Results Intrathecal ketorolac reduced hypersensitivity when it was induced by a combination of ultraviolet burn plus intermittent heat and, according to one of two analytical strategies, when it was induced by ultraviolet burn alone. Conclusions These data suggest a more limited role for spinal cord cyclooxygenase in human pain states than predicted by studies in animals. PMID:20395821

The application of a modified neuroprosthetic hand system in a child with a C7 spinal cord injury. Case report.

PubMed

Smith, B T; Mulcahey, M J; Triolo, R J; Betz, R R

1992-08-01

A neuroprosthetic hand system developed at Case Western Reserve University has been modified for use by an 8 year old child with an incomplete C7 spinal cord injury. This system has been adapted to accommodate voluntary thumb and finger extension, and provides stimulated finger flexion and thumb position for lateral and palmar prehension. Three months were required to develop grasp with sufficient strength and coordination for functional use. This period consisted of: implantation and immobilization of percutaneous intramuscular electrodes; stimulated exercise of the muscles of the hand and forearm; programming grasp patterns; and system training. Functional assessments show that the neuroprosthetic hand system allows the subject to perform unilateral and bilateral tasks that were otherwise impossible or were previously performed bimanually. The ability to perform activities of daily living with one hand frees the contralateral upper extremity to be used either for balance which increases the work area, or to stabilize an object allowing manipulation with the instrumented hand. Telephone interviews suggest that the hand system is used on a consistent basis at home and school. This single subject application indicates that a stimulation system designed for adults with C5-6 spinal cord injuries can enhance hand function and facilitate independence in a child with a low level cervical lesion.

Transverse tripolar spinal cord stimulation: results of an international multicenter study.

PubMed

Oakley, John C; Espinosa, Francisco; Bothe, Hans; McKean, John; Allen, Peter; Burchiel, Kim; Quartey, Gilbert; Spincemaille, Geert; Nuttin, Bart; Gielen, Frans; King, Gary; Holsheimer, Jan

2006-07-01

Experienced neurosurgeons at eight spinal cord stimulation centers in the United States, Canada, and Europe participated in a study from 1997 to 2000 investigating the safety, performance, and efficacy of a Transverse Tripolar Stimulation (TTS) system invented at the University of Twente, the Netherlands. This device was proposed to improve the ability of spinal cord stimulation to adequately overlap paresthesia to perceived areas of pain. Fifty-six patients with chronic, intractable neuropathic pain of the trunk and/or limbs more than three months' duration (average 105 months) were enrolled with follow-up periods at 4, 12, 26, and 52 weeks. All patients had a new paddle-type lead implanted with four electrodes, three of them aligned in a row perpendicular to the cord. Fifteen of these patients did not undergo permanent implantation. Of the 41 patients internalized, 20 patients chose conventional programming using an implanted pulse generator to drive four electrodes, while 21 patients chose a tripole stimulation system, which used radiofrequency power and signal transmission and an implanted dual-channel receiver to drive three electrodes using simultaneous pulses of independently variable amplitude. On average, the visual analog scale scores dropped more for patients with TTS systems (32%) than for conventional polarity systems (16%). Conventional polarity systems were using higher frequencies on average, while usage range was similar. Most impressive was the well-controlled "steering" of the paresthesias according to the dermatomal topography of the dorsal columns when using the TTS-balanced pulse driver. The most common complication was lead migration. While the transverse stimulation system produced acceptable outcomes for overall pain relief, an analysis of individual pain patterns suggests that it behaves like spinal cord stimulation in general with the best control of extremity neuropathic pain. This transverse tripole lead and driving system introduced the concept of electrical field steering by selective recruitment of axonal nerve fiber tracts in the dorsal columns.

Music modulation of pain perception and pain-related activity in the brain, brain stem, and spinal cord: a functional magnetic resonance imaging study.

PubMed

Dobek, Christine E; Beynon, Michaela E; Bosma, Rachael L; Stroman, Patrick W

2014-10-01

The oldest known method for relieving pain is music, and yet, to date, the underlying neural mechanisms have not been studied. Here, we investigate these neural mechanisms by applying a well-defined painful stimulus while participants listened to their favorite music or to no music. Neural responses in the brain, brain stem, and spinal cord were mapped with functional magnetic resonance imaging spanning the cortex, brain stem, and spinal cord. Subjective pain ratings were observed to be significantly lower when pain was administered with music than without music. The pain stimulus without music elicited neural activity in brain regions that are consistent with previous studies. Brain regions associated with pleasurable music listening included limbic, frontal, and auditory regions, when comparing music to non-music pain conditions. In addition, regions demonstrated activity indicative of descending pain modulation when contrasting the 2 conditions. These regions include the dorsolateral prefrontal cortex, periaqueductal gray matter, rostral ventromedial medulla, and dorsal gray matter of the spinal cord. This is the first imaging study to characterize the neural response of pain and how pain is mitigated by music, and it provides new insights into the neural mechanism of music-induced analgesia within the central nervous system. This article presents the first investigation of neural processes underlying music analgesia in human participants. Music modulates pain responses in the brain, brain stem, and spinal cord, and neural activity changes are consistent with engagement of the descending analgesia system. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

Pharmacology for the treatment of premature ejaculation.

PubMed

Giuliano, François; Clèment, Pierre

2012-07-01

Male sexual response comprises four phases: excitement, including erection; plateau; ejaculation, usually accompanied by orgasm; and resolution. Ejaculation is a complex sexual response involving a sequential process consisting of two phases: emission and expulsion. Ejaculation, which is basically a spinal reflex, requires a tight coordination between sympathetic, parasympathetic, and somatic efferent pathways originating from different segments and area in the spinal cord and innervating pelvi-perineal anatomical structures. A major relaying and synchronizing role is played by a group of lumbar neurons described as the spinal generator of ejaculation. Excitatory and inhibitory influences from sensory genital and cerebral stimuli are integrated and processed in the spinal cord. Premature ejaculation (PE) can be defined by ≤1-min ejaculatory latency, an inability to delay ejaculation, and negative personal consequences. Because there is no physiological impairment in PE, any pharmacological agent with central or peripheral mechanism of action that is delaying the ejaculation is a drug candidate for the treatment of PE. Ejaculation is centrally mediated by a variety of neurotransmitter systems, involving especially serotonin and serotonergic pathways but also dopaminergic and oxytocinergic systems. Pharmacological delay of ejaculation can be achieved either by inhibiting excitatory or reinforcing inhibitory pathways from the brain or the periphery to the spinal cord. PE can be treated with long-term use of selective serotonin-reuptake inhibitors (SSRIs) or tricyclic antidepressants. Dapoxetine, a short-acting SSRI, is the first treatment registered for the on-demand treatment of PE. Anesthetics applied on the glans penis have the ability to lengthen the time to ejaculation. Targeting oxytocinergic, neurokinin-1, dopaminergic, and opioid receptors represent future avenues to delaying ejaculation.

Analgesic effect of Minocycline in rat model of inflammation-induced visceral pain

PubMed Central

Kannampalli, Pradeep; Pochiraju, Soumya; Bruckert, Mitchell; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N.

2014-01-01

The present study investigates the analgesic effect of minocycline, a semi-synthetic tetracycline antibiotic, in a rat model of inflammation-induced visceral pain. Inflammation was induced in male rats by intracolonic administration of tri-nitrobenzenesulphonic acid (TNBS). Visceral hyperalgesia was assessed by comparing the viscero-motor response (VMR) to graded colorectal distension (CRD) prior and post 7 days after TNBS treatment. Electrophysiology recordings from CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons were performed in naïve and inflamed rats. Colonic inflammation produced visceral hyperalgesia characterized by increase in the VMRs to CRD accompanied with simultaneous activation of microglia in the spinal cord and satellite glial cells (SGCs) in the dorsal root ganglions (DRGs). Selectively inhibiting the glial activation following inflammation by araC (Arabinofuranosyl Cytidine) prevented the development of visceral hyperalgesia. Intrathecal minocycline significantly attenuated the VMR to CRD in inflamed rats, whereas systemic minocycline produced a delayed effect. In electrophysiology experiments, minocycline significantly attenuated the mechanotransduction of CRD-sensitive PNAs and the responses of CRD-sensitive LS spinal neurons in TNBS-treated rats. While the spinal effect of minocycline was observed within 5 min of administration, systemic injection of the drug produced a delayed effect (60 min) in inflamed rats. Interestingly, minocycline did not exhibit analgesic effect in naïve, non-inflamed rats. The results demonstrate that intrathecal injection of minocycline can effectively attenuate inflammation-induced visceral hyperalgesia. Minocycline might as well act on neuronal targets in the spinal cord of inflamed rats, in addition to the widely reported glial inhibitory action to produce analgesia. PMID:24485889

A novel device for studying weight supported, quadrupedal overground locomotion in spinal cord injured rats.

PubMed

Hamlin, Marvin; Traughber, Terence; Reinkensmeyer, David J; de Leon, Ray D

2015-05-15

Providing weight support facilitates locomotion in spinal cord injured animals. To control weight support, robotic systems have been developed for treadmill stepping and more recently for overground walking. We developed a novel device, the body weight supported ambulatory rodent trainer (i.e. BART). It has a small pneumatic cylinder that moves along a linear track above the rat. When air is supplied to the cylinder, the rats are lifted as they perform overground walking. We tested the BART device in rats that received a moderate spinal cord contusion injury and in normal rats. Locomotor training with the BART device was not performed. All of the rats learned to walk in the BART device. In the contused rats, significantly greater paw dragging and dorsal stepping occurred in the hindlimbs compared to normal. Providing weight support significantly raised hip position and significantly reduced locomotor deficits. Hindlimb stepping was tightly coupled to forelimb stepping but only when the contused rats stepped without weight support. Three weeks after the contused rats received a complete spinal cord transection, significantly fewer hindlimb steps were performed. Relative to rodent robotic systems, the BART device is a simpler system for studying overground locomotion. The BART device lacks sophisticated control and sensing capability, but it can be assembled relatively easily and cheaply. These findings suggest that the BART device is a useful tool for assessing quadrupedal, overground locomotion which is a more natural form of locomotion relative to treadmill locomotion. Published by Elsevier B.V.

A substance P-opioid chimeric peptide as a unique nontolerance-forming analgesic

PubMed Central

Foran, Stacy E.; Carr, Daniel B.; Lipkowski, Andrzej W.; Maszczynska, Iwona; Marchand, James E.; Misicka, Aleksandra; Beinborn, Martin; Kopin, Alan S.; Kream, Richard M.

2000-01-01

To elucidate mechanisms of acute and chronic pain, it is important to understand how spinal excitatory systems influence opioid analgesia. The tachykinin substance P (SP) represents the prototypic spinal excitatory peptide neurotransmitter/neuromodulator, acting in concert with endogenous opioid systems to regulate analgesic responses to nociceptive stimuli. We have synthesized and pharmacologically characterized a chimeric peptide containing overlapping NH2- and COOH-terminal functional domains of the endogenous opioid endomorphin-2 (EM-2) and the tachykinin SP, respectively. Repeated administration of the chimeric molecule YPFFGLM-NH2, designated ESP7, into the rat spinal cord produces opioid-dependent analgesia without loss of potency over 5 days. In contrast, repeated administration of ESP7 with concurrent SP receptor (SPR) blockade results in a progressive loss of analgesic potency, consistent with the development of tolerance. Furthermore, tolerant animals completely regain opioid sensitivity after post hoc administration of ESP7 alone, suggesting that coactivation of SPRs is essential to maintaining opioid responsiveness. Radioligand binding and signaling assays, using recombinant receptors, confirm that ESP7 can coactivate μ-opioid receptors (MOR) and SPRs in vitro. We hypothesize that coincidental activation of the MOR- and SPR-expressing systems in the spinal cord mimics an ongoing state of reciprocal excitation and inhibition, which is normally encountered in nociceptive processing. Due to the ability of ESP7 to interact with both MOR and SPRs, it represents a unique prototypic, anti-tolerance-forming analgesic with future therapeutic potential. PMID:10852965

Distinct functions of opioid-related peptides and gastrin-releasing peptide in regulating itch and pain in the spinal cord of primates.

PubMed

Lee, Heeseung; Ko, Mei-Chuan

2015-06-29

How neuropeptides in the primate spinal cord regulate itch and pain is largely unknown. Here we elucidate the sensory functions of spinal opioid-related peptides and gastrin-releasing peptide (GRP) in awake, behaving monkeys. Following intrathecal administration, β-endorphin (10-100 nmol) and GRP (1-10 nmol) dose-dependently elicit the same degree of robust itch scratching, which can be inhibited by mu-opioid peptide (MOP) receptor and GRP receptor (BB2) antagonists, respectively. Unlike β-endorphin, which produces itch and attenuates inflammatory pain, GRP only elicits itch without affecting pain. In contrast, enkephalins (100-1000 nmol) and nociceptin-orphanin FQ (3-30 nmol) only inhibit pain without eliciting itch. More intriguingly, dynorphin A(1-17) (10-100 nmol) dose-dependently attenuates both β-endorphin- and GRP-elicited robust scratching without affecting pain processing. The anti-itch effects of dynorphin A can be reversed by a kappa-opioid peptide (KOP) receptor antagonist nor-binaltorphimine. These nonhuman primate behavioral models with spinal delivery of ligands advance our understanding of distinct functions of neuropeptides for modulating itch and pain. In particular, we demonstrate causal links for itch-eliciting effects by β-endorphin-MOP receptor and GRP-BB2 receptor systems and itch-inhibiting effects by the dynorphin A-KOP receptor system. These studies will facilitate transforming discoveries of novel ligand-receptor systems into future therapies as antipruritics and/or analgesics in humans.

Magnetic Resonance Characterization of Axonal Response to Spinal Cord Injury

DTIC Science & Technology

2011-10-01

Outcomes 6 Conclusions 6 References 6-29 Appendices Introduction During the first year we pursued studies of Magnetic Resonance q-space imaging...QSI) of the spinal cord and myelin imaging. The QSI studies extended our previous work establishing our ability to define the distribution of axon...Conventional MR imaging of the central nervous systems studies water protons exclusively. Although other compounds, such a lipid and proteins, have

The experience of seeking, gaining and maintaining employment after traumatic spinal cord injury and the vocational pathways involved.

PubMed

Hilton, Gillean; Unsworth, Carolyn A; Stuckey, Ruth; Murphy, Gregory C

2018-01-01

Vocational potential in people with spinal cord injury (SCI) are unrealised with rates of employment substantially lower than in the labour force participation of the general population and the pre-injury employment rates. To understand the experience and pathway of people achieving employment outcome after traumatic spinal cord injury by; classifying participants into employment outcome groups of stable, unstable and without employment; identifying pre and post-injury pathways for participants in each group and, exploring the experiences of people of seeking, gaining and maintaining employment. Thirty-one participants were interviewed. Mixed methods approach including interpretive phenomenological analysis and vocational pathway mapping of quantitative data. The most common pathway identified was from study and work pre-injury to stable employment post-injury. Four super-ordinate themes were identified from the interpretive phenomenological analysis; expectations of work, system impacts, worker identity and social supports. Implications for clinical practice include fostering cultural change, strategies for system navigation, promotion of worker identity and optimal use of social supports. The findings increase insight and understanding of the complex experience of employment after spinal cord injury. There is opportunity to guide experimental research, policy development and education concerning the complexity of the return to work experience and factors that influence pathways.

Hydrogels Derived from Central Nervous System Extracellular Matrix

PubMed Central

Medberry, Christopher J.; Crapo, Peter M.; Siu, Bernard F.; Carruthers, Christopher A.; Wolf, Matthew T.; Nagarkar, Shailesh P.; Agrawal, Vineet; Jones, Kristen E.; Kelly, Jeremy; Johnson, Scott A.; Velankar, Sachin S.; Watkins, Simon C.; Modo, Michel

2012-01-01

Biologic scaffolds composed of extracellular matrix (ECM) are commonly used repair devices in preclinical and clinical settings; however the use of these scaffolds for peripheral and central nervous system (CNS) repair has been limited. Biologic scaffolds developed from brain and spinal cord tissue have recently been described, yet the conformation of the harvested ECM limits therapeutic utility. An injectable CNS-ECM derived hydrogel capable of in vivo polymerization and conformation to irregular lesion geometries may aid in tissue reconstruction efforts following complex neurologic trauma. The objectives of the present study were to develop hydrogel forms of brain and spinal cord ECM and compare the resulting biochemical composition, mechanical properties, and neurotrophic potential of a brain derived cell line to a non-CNS-ECM hydrogel, urinary bladder matrix. Results showed distinct differences between compositions of brain ECM, spinal cord ECM, and urinary bladder matrix. The rheologic modulus of spinal cord ECM hydrogel was greater than that of brain ECM and urinary bladder matrix. All ECMs increased the number of cells expressing neurites, but only brain ECM increased neurite length, suggesting a possible tissue-specific effect. All hydrogels promoted three-dimensional uni- or bi-polar neurite outgrowth following 7 days in culture. These results suggest that CNS-ECM hydrogels may provide supportive scaffolding to promote in vivo axonal repair. PMID:23158935

Paired immunoglobulin-like receptor B knockout does not enhance axonal regeneration or locomotor recovery after spinal cord injury.

PubMed

Nakamura, Yuka; Fujita, Yuki; Ueno, Masaki; Takai, Toshiyuki; Yamashita, Toshihide

2011-01-21

Myelin components that inhibit axonal regeneration are believed to contribute significantly to the lack of axonal regeneration noted in the adult central nervous system. Three proteins found in myelin, Nogo, myelin-associated glycoprotein, and oligodendrocyte-myelin glycoprotein, inhibit neurite outgrowth in vitro. All of these proteins interact with the same receptors, namely, the Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PIR-B). As per previous reports, corticospinal tract (CST) regeneration is not enhanced in NgR-knock-out mice after spinal cord injury. Therefore, we assessed CST regeneration in PIR-B-knock-out mice. We found that hindlimb motor function, as assessed using the Basso mouse scale, footprint test, inclined plane test, and beam walking test, did not differ between the PIR-B-knock-out and wild-type mice after dorsal hemisection of the spinal cord. Further, tracing of the CST fibers after injury did not reveal enhanced axonal regeneration or sprouting in the CST of the PIR-B-knock-out mice. Systemic administration of NEP1-40, a NgR antagonist, to PIR-B knock-out mice did not enhance the regenerative response. These results indicate that PIR-B knock-out is not sufficient to induce extensive axonal regeneration after spinal cord injury.

Electrospun Fibers for Spinal Cord Injury Research and Regeneration

PubMed Central

Schaub, Nicholas J.; Johnson, Christopher D.; Cooper, Blair

2016-01-01

Abstract Electrospinning is the process by which a scaffold containing micrometer and nanometer diameter fibers are drawn from a polymer solution or melt using a large voltage gradient between a polymer emitting source and a grounded collector. Ramakrishna and colleagues first investigated electrospun fibers for neural applications in 2004. After this initial study, electrospun fibers are increasingly investigated for neural tissue engineering applications. Electrospun fibers robustly support axonal regeneration within in vivo rodent models of spinal cord injury. These findings suggest the possibility of their eventual use within patients. Indeed, both spinal cord and peripheral nervous system regeneration research over the last several years shows that physical guidance cues induce recovery of limb, respiration, or bladder control in rodent models. Electrospun fibers may be an alternative to the peripheral nerve graft (PNG), because PNG autografts injure the patient and are limited in supply, and allografts risk host rejection. In addition, electrospun fibers can be engineered easily to confront new therapeutic challenges. Fibers can be modified to release therapies locally or can be physically modified to direct neural stem cell differentiation. This review summarizes the major findings and trends in the last decade of research, with a particular focus on spinal cord injury. This review also demonstrates how electrospun fibers can be used to study the central nervous system in vitro. PMID:26650778

Atypical Teratoid/Rhabdoid Tumor of the Spinal Cord in a Child: Case Report and Comprehensive Review of the Literature.

PubMed

Babgi, Mohammed; Samkari, Alaa; Al-Mehdar, Abeer; Abdullah, Shaker

2018-05-22

Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is characterized by SMARCB1/INI deletion or mutation in the long arm of chromosome 22 11(22q11.2), also resulting in loss of nuclear expression of INI1 protein immunohistochemically. AT/RT tumors usually occur in children below 3 years. The tumor is usually seen in the cerebellum or the cerebrum, with an extremely rare incidence in the spinal cord. We report a rare case of AT/RT in a 6-year-old boy who had a primary spinal cord lesion in the thoracolumbar junction. Pathology revealed loss of nuclear staining of INI1 immunohistochemically. This is the first case reported with mixed intraspinal lesion (intra- and extramedullary). The patient underwent two surgeries and received radiotherapy and chemotherapy; however, he died 16 months after the initial presentation. We reviewed the literature on all children with spinal cord AT/RT. The review showed that the cervical region is the most common location of origin, especially in younger children. Reported cases were treated with a combination of surgery, systemic and intrathecal chemotherapy, and radiation therapy, and a survival time of 18 months represented the best outcome. Overall mean survival time was 10 months. © 2018 S. Karger AG, Basel.

Notch Signaling Pathway Is Activated in Motoneurons of Spinal Muscular Atrophy

PubMed Central

Caraballo-Miralles, Víctor; Cardona-Rossinyol, Andrea; Garcera, Ana; Torres-Benito, Laura; Soler, Rosa M.; Tabares, Lucía; Lladó, Jerònia; Olmos, Gabriel

2013-01-01

Spinal muscular atrophy (SMA) is a neurodegenerative disease produced by low levels of Survival Motor Neuron (SMN) protein that affects alpha motoneurons in the spinal cord. Notch signaling is a cell-cell communication system well known as a master regulator of neural development, but also with important roles in the adult central nervous system. Aberrant Notch function is associated with several developmental neurological disorders; however, the potential implication of the Notch pathway in SMA pathogenesis has not been studied yet. We report here that SMN deficiency, induced in the astroglioma cell line U87MG after lentiviral transduction with a shSMN construct, was associated with an increase in the expression of the main components of Notch signaling pathway, namely its ligands, Jagged1 and Delta1, the Notch receptor and its active intracellular form (NICD). In the SMNΔ7 mouse model of SMA we also found increased astrocyte processes positive for Jagged1 and Delta1 in intimate contact with lumbar spinal cord motoneurons. In these motoneurons an increased Notch signaling was found, as denoted by increased NICD levels and reduced expression of the proneural gene neurogenin 3, whose transcription is negatively regulated by Notch. Together, these findings may be relevant to understand some pathologic attributes of SMA motoneurons. PMID:23759991

New, Improved Version of the mCOP-PCR Screening System for Detection of Spinal Muscular Atrophy Gene (SMN1) Deletion.

PubMed

Shinohara, Masakazu; Ar Rochmah, Mawaddah; Nakanishi, Kenta; Harahap, Nur Imma Fatimah; Niba, Emma Tabe Eko; Saito, Toshio; Saito, Kayoko; Takeuchi, Atsuko; Bouike, Yoshihiro; Nishio, Hisahide

2017-09-07

Spinal muscular atrophy (SMA) is a frequent autosomal recessive disorder, characterized by lower motor neuron loss in the spinal cord. More than 95% of SMA patients show homozygous survival motor neuron 1 (SMN1) deletion. We previously developed a screening system for SMN1 deletion based on a modified competitive oligonucleotide priming-PCR (mCOP-PCR) technique. However, non-specific amplification products were observed with mCOP-PCR, which might lead to erroneous interpretation of the screening results. To establish an improved version of the mCOP-PCR screening system without non-specific amplification. DNA samples were assayed using a new version of the mCOP-PCR screening system. DNA samples had already been genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP), showing the presence or absence of SMN1 exon 7. The new mCOP-PCR method contained a targeted pre-amplification step of the region, including an SMN1-specific nucleotide, prior to the mCOP-PCR step. mCOP-PCR products were electrophoresed on agarose gels. No non-specific amplification products were detected in electrophoresis gels with the new mCOP-PCR screening system. An additional targeted pre-amplification step eliminated non-specific amplification from mCOP-PCR screening.

Changes in rat spinal cord gene expression after inflammatory hyperalgesia of the joint and manual therapy.

PubMed

Ruhlen, Rachel L; Singh, Vineet K; Pazdernik, Vanessa K; Towns, Lex C; Snider, Eric J; Sargentini, Neil J; Degenhardt, Brian F

2014-10-01

Mobilization of a joint affects local tissue directly but may also have other effects that are mediated through the central nervous system. To identify differential gene expression in the spinal cords of rats with or without inflammatory joint injury after manual therapy or no treatment. Rats were randomly assigned to 1 of 4 treatment groups: no injury and no touch (NI/NT), injury and no touch (I/NT), no injury and manual therapy (NI/MT), and injury and manual therapy (I/MT). We induced acute inflammatory joint injury in the rats by injecting carrageenan into an ankle. Rats in the no-injury groups did not receive carrageenan injection. One day after injury, rats received manual therapy to the knee of the injured limb. Rats in the no-touch groups were anesthetized without receiving manual therapy. Spinal cords were harvested 30 minutes after therapy or no touch, and spinal cord gene expression was analyzed by microarray for 3 comparisons: NI/NT vs I/NT, I/MT vs I/NT, and NI/NT vs NI/MT. Three rats were assigned to each group. Of 38,875 expressed sequence tags, 755 were differentially expressed in the NI/NT vs I/NT comparison. For the other comparisons, no expressed sequence tags were differentially expressed. Cluster analysis revealed that the differentially expressed sequence tags were over-represented in several categories, including ion homeostasis (enrichment score, 2.29), transmembrane (enrichment score, 1.55), and disulfide bond (enrichment score, 2.04). An inflammatory injury to the ankle of rats caused differential expression of genes in the spinal cord. Consistent with other studies, genes involved in ion transport were among those affected. However, manual therapy to the knees of injured limbs or to rats without injury did not alter gene expression in the spinal cord. Thus, evidence for central nervous system mediation of manual therapy was not observed. © 2014 The American Osteopathic Association.

Weight-Bearing Locomotion in the Developing Opossum, Monodelphis domestica following Spinal Transection: Remodeling of Neuronal Circuits Caudal to Lesion

PubMed Central

Wheaton, Benjamin J.; Noor, Natassya M.; Whish, Sophie C.; Truettner, Jessie S.; Dietrich, W. Dalton; Zhang, Moses; Crack, Peter J.; Dziegielewska, Katarzyna M.; Saunders, Norman R.

2013-01-01

Complete spinal transection in the mature nervous system is typically followed by minimal axonal repair, extensive motor paralysis and loss of sensory functions caudal to the injury. In contrast, the immature nervous system has greater capacity for repair, a phenomenon sometimes called the infant lesion effect. This study investigates spinal injuries early in development using the marsupial opossum Monodelphis domestica whose young are born very immature, allowing access to developmental stages only accessible in utero in eutherian mammals. Spinal cords of Monodelphis pups were completely transected in the lower thoracic region, T10, on postnatal-day (P)7 or P28 and the animals grew to adulthood. In P7-injured animals regrown supraspinal and propriospinal axons through the injury site were demonstrated using retrograde axonal labelling. These animals recovered near-normal coordinated overground locomotion, but with altered gait characteristics including foot placement phase lags. In P28-injured animals no axonal regrowth through the injury site could be demonstrated yet they were able to perform weight-supporting hindlimb stepping overground and on the treadmill. When placed in an environment of reduced sensory feedback (swimming) P7-injured animals swam using their hindlimbs, suggesting that the axons that grew across the lesion made functional connections; P28-injured animals swam using their forelimbs only, suggesting that their overground hindlimb movements were reflex-dependent and thus likely to be generated locally in the lumbar spinal cord. Modifications to propriospinal circuitry in P7- and P28-injured opossums were demonstrated by changes in the number of fluorescently labelled neurons detected in the lumbar cord following tracer studies and changes in the balance of excitatory, inhibitory and neuromodulatory neurotransmitter receptors’ gene expression shown by qRT-PCR. These results are discussed in the context of studies indicating that although following injury the isolated segment of the spinal cord retains some capability of rhythmic movement the mechanisms involved in weight-bearing locomotion are distinct. PMID:23951105

Weight-bearing locomotion in the developing opossum, Monodelphis domestica following spinal transection: remodeling of neuronal circuits caudal to lesion.

PubMed

Wheaton, Benjamin J; Noor, Natassya M; Whish, Sophie C; Truettner, Jessie S; Dietrich, W Dalton; Zhang, Moses; Crack, Peter J; Dziegielewska, Katarzyna M; Saunders, Norman R

2013-01-01

Complete spinal transection in the mature nervous system is typically followed by minimal axonal repair, extensive motor paralysis and loss of sensory functions caudal to the injury. In contrast, the immature nervous system has greater capacity for repair, a phenomenon sometimes called the infant lesion effect. This study investigates spinal injuries early in development using the marsupial opossum Monodelphis domestica whose young are born very immature, allowing access to developmental stages only accessible in utero in eutherian mammals. Spinal cords of Monodelphis pups were completely transected in the lower thoracic region, T10, on postnatal-day (P)7 or P28 and the animals grew to adulthood. In P7-injured animals regrown supraspinal and propriospinal axons through the injury site were demonstrated using retrograde axonal labelling. These animals recovered near-normal coordinated overground locomotion, but with altered gait characteristics including foot placement phase lags. In P28-injured animals no axonal regrowth through the injury site could be demonstrated yet they were able to perform weight-supporting hindlimb stepping overground and on the treadmill. When placed in an environment of reduced sensory feedback (swimming) P7-injured animals swam using their hindlimbs, suggesting that the axons that grew across the lesion made functional connections; P28-injured animals swam using their forelimbs only, suggesting that their overground hindlimb movements were reflex-dependent and thus likely to be generated locally in the lumbar spinal cord. Modifications to propriospinal circuitry in P7- and P28-injured opossums were demonstrated by changes in the number of fluorescently labelled neurons detected in the lumbar cord following tracer studies and changes in the balance of excitatory, inhibitory and neuromodulatory neurotransmitter receptors' gene expression shown by qRT-PCR. These results are discussed in the context of studies indicating that although following injury the isolated segment of the spinal cord retains some capability of rhythmic movement the mechanisms involved in weight-bearing locomotion are distinct.

Effect of Surgical Approach on Pulmonary Function in Adolescent Idiopathic Scoliosis Patients: A Systemic Review and Meta-analysis.

PubMed

Lee, Andy C H; Feger, Mark A; Singla, Anuj; Abel, Mark F

2016-11-15

Systemic review and meta-analysis. To analyze the effect of spinal fusion and instrumentation for adolescent idiopathic scoliosis (AIS) on absolute pulmonary function test (PFTs). Pulmonary function is correlated with severity of deformity in AIS patients and studies that have analyzed the effect of spinal fusion and instrumentation on PFTs for AIS have reported inconsistent results. There is a need to analyze the effect of spinal fusion on PFTs with stratification by surgical approach. Our analysis included 22 studies. Cohen's d effect sizes were calculated for absolute PFT outcome measures with 95% confidence intervals (CI). Meta-analyses were performed at each postoperative time frame for six homogeneous surgical approaches: (i) combined anterior release and posterior fusion with instrumentation; (ii) combined video assisted anterior release and posterior fusion with instrumentation without thoracoplasty; (iii) posterior fusion with instrumentation without thoracoplasty; (iv) anterior fusion with instrumentation and without thoracoplasty; (v) video assisted anterior fusion with instrumentation without thoracoplasty; and (vi) any scoliosis surgery with additional thoracoplasty. Anterior spinal fusion with instrumentation, any scoliosis surgery with concomitant thoracoplasty, or video-assisted anterior fusion with instrumentation for AIS had similar absolute PFTs at their 2 year postoperative follow up compared with their preoperative PFTs (effect sizes ranging from -0.2-0.2 with all CI crossing "0"). Posterior spinal fusion with instrumentation (with or without an anterior release) demonstrated small to moderate increases in PFTs 2 years postoperatively (effect sizes ranging from 0.35-0.65 with all CI not crossing "0"). Anterior fusion with instrumentation, regardless of the approach, and any scoliosis surgery with concomitant thoracoplasty do not lead to significant change in pulmonary functions 2 year after surgery. Posterior spinal fusion with instrumentation (with or without an anterior release) resulted in small to moderate increases in PFTs. N/A.

Modulation of spinal nociception by GluR5 kainate receptor ligands in acute and hyperalgesic states and the role of gabaergic mechanisms.

PubMed

Mascias, Paula; Scheede, Manuela; Bloms-Funke, Petra; Chizh, Boris

2002-09-01

GluR5 receptors modulate spinal nociception, however, their role in nociceptive hypersensitivity remains unclear. Using behavioural and electrophysiological approaches, we have investigated several GluR5 ligands in acute and hyperalgesic states. Furthermore, as the GABAergic system plays a role in GluR5 mediated effects in the brain, we also analysed the interaction between GluR5 agonists and GABA(A) antagonists in the spinal cord. In young rats in vivo, the GluR5 selective agonist ATPA was antinociceptive and antihyperalgesic in a model of inflammatory hyperalgesia (ED(50) approximately 4.6 and approximately 5.2 mg/kg, respectively), whereas the GluR5/GluR6 agonist SYM2081 was only antihyperalgesic. ATPA, but not SYM2081, was also able to inhibit nociceptive motoneurone responses in anaesthetised adult rats after intrathecal administration. In hemisected spinal cords in vitro, SYM2081 was inactive, whereas ATPA and another GluR5 agonist, (S)-5-iodowillardiine, inhibited nociceptive reflexes (EC(50) 1.1+/-0.4 micro M and 0.36+/-0.05 micro M, respectively). Both GluR5 agonists also inhibited motoneurone responses to repetitive dorsal root stimulation and their cumulative depolarisation, a correlate of wind-up. The GABA(A) antagonists bicuculline (10 micro M) and SR95531 (1 micro M) enhanced polysynaptic responses to single stimuli but abolished the cumulative depolarisation. Both bicuculline and SR95531 significantly attenuated the inhibition of nociceptive responses by 1 micro M ATPA (by approximately 50%). We conclude that selective GluR5 kainate receptor activation inhibits spinal nociception and its sensitisation caused by ongoing peripheral nociceptive drive. GABA(A) receptors are involved in tonic inhibition of segmental responses, but contribute to their sensitisation by repetitive primary afferent stimulation. Furthermore, there is a cross-talk between the two systems, presumably due to GluR5-mediated activation of GABAergic inhibitory interneurones in the spinal cord.

Direct plan comparison of RapidArc and CyberKnife for spine stereotactic body radiation therapy

NASA Astrophysics Data System (ADS)

Choi, Young Eun; Kwak, Jungwon; Song, Si Yeol; Choi, Eun Kyung; Ahn, Seung Do; Cho, Byungchul

2015-07-01

We compared the treatment planning performance of RapidArc (RA) vs. CyberKnife (CK) for spinal stereotactic body radiation therapy (SBRT). Ten patients with spinal lesions who had been treated with CK were re-planned with RA, which consisted of two complete arcs. Computed tomography (CT) and volumetric dose data of CK, generated using the Multiplan (Accuray) treatment planning system (TPS) and the Ray-trace algorithm, were imported to Varian Eclipse TPS in Dicom format, and the data were compared with the RA plan by using an analytical anisotropic algorithm (AAA) dose calculation. The optimized dose priorities for both the CK and the RA plans were similar for all patients. The highest priority was to provide enough dose coverage to the planned target volume (PTV) while limiting the maximum dose to the spinal cord. Plan quality was evaluated with respect to PTV coverage, conformity index (CI), high-dose spillage, intermediate-dose spillage (R50% and D2cm), and maximum dose to the spinal cord, which are criteria recommended by the RTOG 0631 spine and 0915 lung SBRT protocols. The mean CI' SD values of the PTV were 1.11' 0.03 and 1.17' 0.10 for RA and CK ( p = 0.02), respectively. On average, the maximum dose delivered to the spinal cord in CK plans was approximately 11.6% higher than that in RA plans, and this difference was statistically significant ( p < 0.001). High-dose spillages were 0.86% and 2.26% for RA and CK ( p = 0.203), respectively. Intermediate-dose spillage characterized by D2cm was lower for RA than for CK; however, R50% was not statistically different. Even though both systems can create highly conformal volumetric dose distributions, the current study shows that RA demonstrates lower high- and intermediate-dose spillages than CK. Therefore, RA plans for spinal SBRT may be superior to CK plans.

Elevated Levels of Calcitonin Gene-Related Peptide in Upper Spinal Cord Promotes Sensitization of Primary Trigeminal Nociceptive Neurons

PubMed Central

Cornelison, Lauren E.; Hawkins, Jordan L.; Durham, Paul L.

2016-01-01

Orofacial pain conditions including temporomandibular joint disorder and migraine are characterized by peripheral and central sensitization of trigeminal nociceptive neurons. Although calcitonin gene-related peptide (CGRP) is implicated in the development of central sensitization, the pathway by which elevated spinal cord CGRP levels promote peripheral sensitization of primary trigeminal nociceptive neurons is not well understood. The goal of this study was to investigate the role of CGRP in promoting bidirectional signaling within the trigeminal system to mediate sensitization of primary trigeminal ganglion nociceptive neurons. Adult male Sprague Dawley rats were injected in the upper spinal cord with CGRP or co-injected with the receptor antagonist CGRP8-37 or KT 5720, an inhibitor of protein kinase A (PKA). Nocifensive head withdrawal response to mechanical stimulation of trigeminal nerves was investigated using von Frey filaments. Expression of PKA, GFAP, and Iba1 in the spinal cord and P-ERK in the trigeminal ganglion was studied using immunohistochemistry. Some animals were co-injected intracisternally with CGRP and Fast Blue dye and trigeminal ganglion imaged using fluorescent microscopy. Intracisternal CGRP increased nocifensive responses to mechanical stimulation when compared to control levels. Co-injection of CGRP8-37 or KT 5720 with CGRP inhibited the nocifensive response. CGRP stimulated expression of PKA and GFAP in the spinal cord, and P-ERK in trigeminal ganglion neurons. Seven days post injection, Fast Blue was observed in trigeminal ganglion neurons and satellite glial cells. Our results demonstrate that elevated levels of CGRP in the upper spinal cord promote sensitization of primary trigeminal nociceptive neurons via a mechanism that involves activation of PKA centrally and P-ERK in trigeminal ganglion neurons. Our findings provide evidence of bidirectional signaling within the trigeminal system that can facilitate increased neuron-glia communication within the trigeminal ganglion associated with peripheral sensitization. PMID:27746346

Internal validation of the prognostic index for spine metastasis (PRISM) for stratifying survival in patients treated with spinal stereotactic radiosurgery.

PubMed

Jensen, Garrett; Tang, Chad; Hess, Kenneth R; Bishop, Andrew J; Pan, Hubert Y; Li, Jing; Yang, James N; Tannir, Nizar M; Amini, Behrang; Tatsui, Claudio; Rhines, Laurence; Brown, Paul D; Ghia, Amol J

2017-01-01

We sought to validate the Prognostic Index for Spinal Metastases (PRISM), a scoring system that stratifies patients into subgroups by overall survival.Methods and materials: The PRISM was previously created from multivariate Cox regression with patients enrolled in prospective single institution trials of stereotactic spine radiosurgery (SSRS) for spinal metastasis. We assess model calibration and discrimination within a validation cohort of patients treated off-trial with SSRS for metastatic disease at the same institution. The training and validation cohorts consisted of 205 and 249 patients respectively. Similar survival trends were shown in the 4 PRISM. Survival was significantly different between PRISM subgroups (P<0.0001). C-index for the validation cohort was 0.68 after stratification into subgroups. We internally validated the PRISM with patients treated off-protocol, demonstrating that it can distinguish subgroups by survival, which will be useful for individualizing treatment of spinal metastases and stratifying patients for clinical trials.

Cortical control of intraspinal microstimulation: Toward a new approach for restoration of function after spinal cord injury.

PubMed

Shahdoost, Shahab; Frost, Shawn; Dunham, Caleb; DeJong, Stacey; Barbay, Scott; Nudo, Randolph; Mohseni, Pedram

2015-08-01

Approximately 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress toward developing a miniaturized brain-machine-spinal cord interface (BMSI) that converts in real time the neural command signals recorded from the cortical motor regions to electrical stimuli delivered to the spinal cord below the injury level. Using a combination of custom integrated circuit (IC) technology for corticospinal interfacing and field-programmable gate array (FPGA)-based technology for embedded signal processing, we demonstrate proof-of-concept of distinct muscle pattern activation via intraspinal microstimulation (ISMS) controlled in real time by intracortical neural spikes in an anesthetized laboratory rat.

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

PubMed Central

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

2015-01-01

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

M.I.T./Canadian vestibular experiments on the Spacelab-1 mission: 3. Effects of prolonged weightlessness on a human otolith-spinal reflex

NASA Technical Reports Server (NTRS)

Watt, D. G.; Money, K. E.; Tomi, L. M.

1986-01-01

Reflex responses that depend on human otolith organ sensitivity were measured before, during and after a 10 day space flight. Otolith-spinal reflexes were elicited by means of sudden, unexpected falls. In weightlessness, "falls" were achieved using elastic cords running from a torso harness to the floor. Electromyographic (EMG) activity was recorded from gastrocnemius-soleus. The EMG response occurring in the first 100-120 ms of a fall, considered to be predominantly otolith-spinal in origin, decreased in amplitude immediately upon entering weightlessness, and continued to decline throughout the flight, especially during the first two mission days. The response returned to normal before the first post-flight testing session. The results suggest that information coming from the otolith organs is gradually ignored by the nervous system during prolonged space flight, although the possibility that otolith-spinal reflexes are decreased independent of other otolith output pathways cannot be ruled out.

M.I.T./Canadian vestibular experiments on the Spacelab-1 mission. III - Effects of prolonged weightlessness on a human otolith-spinal reflex

NASA Technical Reports Server (NTRS)

Watt, D. G. D.; Money, K. E.; Tomi, L. M.

1986-01-01

Reflex responses that depend on human otolith organ sensitivity were measured before, during and after a 10 day space flight. Otolith-spinal reflexes were elicited by means of sudden, unexpected falls. In weightlessness, 'falls' were achieved using elastic cords running from a torso harness to the floor. Electromyographic (EMG) activity was recorded from gastrocnemius-soleus. The EMG response occurring in the first 100-120 ms of a fall, considered to be predominantly otolith-spinal in origin, decreased in amplitude immediately upon entering weightlessness, and continued to decline throughout the flight, especially during the first two mission days. The response returned to normal before the first post-flight testing session. The results suggest that information coming from the otolith organs is gradually ignored by the nervous system during prolonged space flight, although the possibility that otolith-spinal reflexes are decreased independent of other otolith output pathways cannot by ruled out.

Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury

PubMed Central

Fairbanks, Carolyn A.; Schreiber, Kristin L.; Brewer, Kori L.; Yu, Chen-Guang; Stone, Laura S.; Kitto, Kelley F.; Nguyen, H. Oanh; Grocholski, Brent M.; Shoeman, Don W.; Kehl, Lois J.; Regunathan, Soundararajan; Reis, Donald J.; Yezierski, Robert P.; Wilcox, George L.

2000-01-01

Antagonists of glutamate receptors of the N-methyl-d-aspartate subclass (NMDAR) or inhibitors of nitric oxide synthase (NOS) prevent nervous system plasticity. Inflammatory and neuropathic pain rely on plasticity, presenting a clinical opportunity for the use of NMDAR antagonists and NOS inhibitors in chronic pain. Agmatine (AG), an endogenous neuromodulator present in brain and spinal cord, has both NMDAR antagonist and NOS inhibitor activities. We report here that AG, exogenously administered to rodents, decreased hyperalgesia accompanying inflammation, normalized the mechanical hypersensitivity (allodynia/hyperalgesia) produced by chemical or mechanical nerve injury, and reduced autotomy-like behavior and lesion size after excitotoxic spinal cord injury. AG produced these effects in the absence of antinociceptive effects in acute pain tests. Endogenous AG also was detected in rodent lumbosacral spinal cord in concentrations similar to those previously detected in brain. The evidence suggests a unique antiplasticity and neuroprotective role for AG in processes underlying persistent pain and neuronal injury. PMID:10984543

Dissection and lateral mounting of zebrafish embryos: analysis of spinal cord development.

PubMed

Beck, Aaron P; Watt, Roland M; Bonner, Jennifer

2014-02-28

The zebrafish spinal cord is an effective investigative model for nervous system research for several reasons. First, genetic, transgenic and gene knockdown approaches can be utilized to examine the molecular mechanisms underlying nervous system development. Second, large clutches of developmentally synchronized embryos provide large experimental sample sizes. Third, the optical clarity of the zebrafish embryo permits researchers to visualize progenitor, glial, and neuronal populations. Although zebrafish embryos are transparent, specimen thickness can impede effective microscopic visualization. One reason for this is the tandem development of the spinal cord and overlying somite tissue. Another reason is the large yolk ball, which is still present during periods of early neurogenesis. In this article, we demonstrate microdissection and removal of the yolk in fixed embryos, which allows microscopic visualization while preserving surrounding somite tissue. We also demonstrate semipermanent mounting of zebrafish embryos. This permits observation of neurodevelopment in the dorso-ventral and anterior-posterior axes, as it preserves the three-dimensionality of the tissue.

Dissection and Lateral Mounting of Zebrafish Embryos: Analysis of Spinal Cord Development

PubMed Central

Beck, Aaron P.; Watt, Roland M.; Bonner, Jennifer

2014-01-01

The zebrafish spinal cord is an effective investigative model for nervous system research for several reasons. First, genetic, transgenic and gene knockdown approaches can be utilized to examine the molecular mechanisms underlying nervous system development. Second, large clutches of developmentally synchronized embryos provide large experimental sample sizes. Third, the optical clarity of the zebrafish embryo permits researchers to visualize progenitor, glial, and neuronal populations. Although zebrafish embryos are transparent, specimen thickness can impede effective microscopic visualization. One reason for this is the tandem development of the spinal cord and overlying somite tissue. Another reason is the large yolk ball, which is still present during periods of early neurogenesis. In this article, we demonstrate microdissection and removal of the yolk in fixed embryos, which allows microscopic visualization while preserving surrounding somite tissue. We also demonstrate semipermanent mounting of zebrafish embryos. This permits observation of neurodevelopment in the dorso-ventral and anterior-posterior axes, as it preserves the three-dimensionality of the tissue. PMID:24637734

Control of cancer pain by epidural infusion of morphine.

PubMed

Waterman, N G; Hughes, S; Foster, W S

1991-10-01

Pain that cannot be controlled by traditional oral and parenteral methods in those patients with advanced cancer can be alleviated by spinal administration of narcotics. Epidural and intrathecal infusion with morphine causes analgesia by blocking spinal receptors without significant long-term central nervous, gastrointestinal, and genitourinary system effects. Of the total of 33 patients, epidural catheters inserted in 20 patients then connected by a subcutaneous tunnel to a continuous infusion system. Implanted pumps were used in each of these patients. Because of the cost and limitations of the implanted pumps, epidural catheters were connected, either directly or by subcutaneous reservoirs, to external ambulatory infusion pumps in the remaining 13 patients. Patient assessment by a linear analogue scale to measure pain levels determined that 23 of the 33 total patients (70%) had excellent or good relief of pain. The delivery of spinal administration of narcotics to treat intractable cancer pain in patients is safe. Most importantly, this method of delivery can be used in community hospitals, in outpatient settings, and in home health care programs.

A computer-controlled, closed-loop infusion system for infusing muscle relaxants: its use during motor-evoked potential monitoring.

PubMed

Stinson, L W; Murray, M J; Jones, K A; Assef, S J; Burke, M J; Behrens, T L; Lennon, R L

1994-02-01

A microcomputer-controlled closed-loop infusion system (MCCLIS) has been developed that provides stable intraoperative levels of partial neuromuscular blockade. Complete neuromuscular blockade interferes with intraoperative motor-evoked potential (MEP) monitoring used for patients undergoing surgical procedures that place them at risk for spinal cord ischemia. Nine patients were studied during which the MCCLIS maintained stable levels of partial neuromuscular blockade and allowed transcranial magnetic motor-evoked potential (TcM-MEP) monitoring during thoracoabdominal aortic aneurysmectomy. The use of TcM-MEP for monitoring intraoperative spinal cord function was balanced against surgical considerations for muscle relaxation with 80% to 90% neuromuscular blockade fulfilling each requirement. Intraoperative adjustment of partial neuromuscular blockade to facilitate TcM-MEP monitoring was also possible with the MCCLIS. The MCCLIS should allow for further investigation into the sensitivity, specificity, and predictability of TcM-MEP monitoring for any patient at risk for intraoperative spinal cord ischemia including those undergoing thoracoabdominal aortic aneurysmectomy.

Response properties of nucleus reticularis lateralis neurons after electroacupuncture stimulation in rats.

PubMed

Moritaka, Kentaro; Zeredo, Jorge L; Kimoto, Mari; Nasution, Fajar H; Hirano, Takafumi; Toda, Kazuo

2010-01-01

A descending inhibitory mechanism from the periaqueductal gray (PAG) to the spinal cord through the nucleus raphe magnus (NRM) is strongly involved in endogenous analgesic system produced by acupuncture stimulation. In addition to the PAG to NRM system which descends in the medial pathway of the brain stem, the nucleus reticularis lateralis (NRL) situated in the lateral part of the brain stem is reported to play an important role in modulating centrifugal antinociceptive action. In the present study, to clarify the role of NRL in acupuncture analgesia, we investigated the response properties of NRL neurons to acupuncture stimulation. The majority of NRM-projecting NRL neurons were inhibited by electroacupuncture stimulation. This effect was antagonized by ionophoretic application of naloxone, indicating that endogenous opioids act directly onto these NRL neurons. By contrast, about half of spinal projecting NRL neurons were excited by electroacupuncture stimulation, suggesting that part of the NRL neurons may modulate pain transmission directly at the spinal level.

Monitorization of the effects of spinal anaesthesia on cerebral oxygen saturation in elder patients using near-infrared spectroscopy.

PubMed

Kusku, Aysegul; Demir, Guray; Cukurova, Zafer; Eren, Gulay; Hergunsel, Oya

2014-01-01

Central blockage provided by spinal anaesthesia enables realization of many surgical procedures, whereas hemodynamic and respiratory changes influence systemic oxygen delivery leading to the potential development of series of problems such as cerebral ischemia, myocardial infarction and acute renal failure. This study was intended to detect potentially adverse effects of hemodynamic and respiratory changes on systemic oxygen delivery using cerebral oxymetric methods in patients who underwent spinal anaesthesia. Twenty-five ASA I-II Group patients aged 65-80 years scheduled for unilateral inguinal hernia repair under spinal anaesthesia were included in the study. Following standard monitorization baseline cerebral oxygen levels were measured using cerebral oximetric methods. Standardized Mini Mental Test (SMMT) was applied before and after the operation so as to determine the level of cognitive functioning of the cases. Using a standard technique and equal amounts of a local anaesthetic drug (15mg bupivacaine 5%) intratechal blockade was performed. Mean blood pressure (MBP), maximum heart rate (MHR), peripheral oxygen saturation (SpO2) and cerebral oxygen levels (rSO2) were preoperatively monitored for 60min. Pre- and postoperative haemoglobin levels were measured. The variations in data obtained and their correlations with the cerebral oxygen levels were investigated. Significant changes in pre- and postoperative measurements of haemoglobin levels and SMMT scores and intraoperative SpO2 levels were not observed. However, significant variations were observed in intraoperative MBP, MHR and rSO2 levels. Besides, a correlation between variations in rSO2, MBP and MHR was determined. Evaluation of the data obtained in the study demonstrated that post-spinal decline in blood pressure and also heart rate decreases systemic oxygen delivery and adversely effects cerebral oxygen levels. However, this downward change did not result in deterioration of cognitive functioning. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[Monitorization of the effects of spinal anaesthesia on cerebral oxygen saturation in elder patients using near-infrared spectroscopy].

PubMed

Kusku, Aysegul; Demir, Guray; Cukurova, Zafer; Eren, Gulay; Hergunsel, Oya

2014-01-01

Central blockage provided by spinal anaesthesia enables realization of many surgical procedures, whereas hemodynamic and respiratory changes influence systemic oxygen delivery leading to the potential development of series of problems such as cerebral ischemia, myocardial infarction and acute renal failure. This study was intended to detect potentially adverse effects of hemodynamic and respiratory changes on systemic oxygen delivery using cerebral oxymetric methods in patients who underwent spinal anaesthesia. Twenty-five ASA I-II Group patients aged 65-80 years scheduled for unilateral inguinal hernia repair under spinal anaesthesia were included in the study. Following standard monitorization baseline cerebral oxygen levels were measured using cerebral oximetric methods. Standardized Mini Mental Test (SMMT) was applied before and after the operation so as to determine the level of cognitive functioning of the cases. Using a standard technique and equal amounts of a local anaesthetic drug (15mg bupivacaine 5%) intratechal blockade was performed. Mean blood pressure (MBP), maximum heart rate (MHR), peripheral oxygen saturation (SpO2) and cerebral oxygen levels (rSO2) were preoperatively monitored for 60min. Pre- and postoperative haemoglobin levels were measured. The variations in data obtained and their correlations with the cerebral oxygen levels were investigated. Significant changes in pre- and postoperative measurements of haemoglobin levels and SMMT scores and intraoperative SpO2 levels were not observed. However, significant variations were observed in intraoperative MBP, MHR and rSO2 levels. Besides, a correlation between variations in rSO2, MBP and MHR was determined. Evaluation of the data obtained in the study demonstrated that post-spinal decline in blood pressure and also heart rate decreases systemic oxygen delivery and adversely effects cerebral oxygen levels. However, this downward change did not result in deterioration of cognitive functioning. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Autonomic cardiovascular control and sports classification in Paralympic athletes with spinal cord injury.

PubMed

West, Christopher R; Krassioukov, Andrei V

2017-01-01

Purpose To investigate the relationship between the classification systems used in wheelchair sports and cardiovascular function in Paralympic athletes with spinal cord injury (SCI). Methods 26 wheelchair rugby (C3-C8) and 14 wheelchair basketball (T3-L1) were assessed for their International Wheelchair Rugby and Basketball Federation sports classification. Next, athletes were assessed for resting and reflex cardiovascular and autonomic function via the change (delta) in systolic blood pressure (SBP) and heart rate (HR) in response to sit-up, and sympathetic skin responses (SSRs), respectively. Results There were no differences in supine, seated, or delta SBP and HR between different sport classes in rugby or basketball (all p > 0.23). Athletes with autonomically complete injuries (SSR score 0-1) exhibited a lower supine SBP, seated SBP and delta SBP compared to those with autonomically incomplete injuries (SSR score >1; all p < 0.010), independent of sport played. There was no association between self-report OH and measured OH (χ 2  =   1.63, p = 0.20). Conclusion We provide definitive evidence that sports specific classification is not related to the degree of remaining autonomic cardiovascular control in Paralympic athletes with SCI. We suggest that testing for remaining autonomic function, which is closely related to the degree of cardiovascular control, should be incorporated into sporting classification. Implications for Rehabilitation Spinal cord injury is a debilitating condition that affects the function of almost every physiological system. It is becoming increasingly apparent that spinal cord injury induced changes in autonomic and cardiovascular function are important determinants of sports performance in athletes with spinal cord injury. This study shows that the current sports classification systems used in wheelchair rugby and basketball do not accurately reflect autonomic and cardiovascular function and thus are placing some athletes at a distinct disadvantage/advantage within their respective sport.

Nucleus reticularis gigantocellularis and nucleus raphe magnus in the brain stem exert opposite effects on behavioral hyperalgesia and spinal Fos protein expression after peripheral inflammation.

PubMed

Wei, F; Dubner, R; Ren, K

1999-03-01

Previous findings indicate that the brain stem descending system becomes more active in modulating spinal nociceptive processes during the development of persistent pain. The present study further identified the supraspinal sites that mediate enhanced descending modulation of behavior hyperalgesia and dorsal horn hyperexcitability (as measured by Fos-like immunoreactivity) produced by subcutaneous complete Freund's adjuvant (CFA). Selective chemical lesions were produced in the nucleus raphe magnus (NRM), the nuclei reticularis gigantocellularis (NGC), or the locus coeruleus/subcoeruleus (LC/SC). Compared to vehicle-injected animals with injection of vehicle alone, microinjection of a serotoninergic neurotoxin 5,7-dihydroxytryptamine into the NRM significantly increased thermal hyperalgesia and Fos protein expression in lumbar spinal cord after hindpaw inflammation. In contrast, the selective bilateral destruction of the NGC with a soma-selective excitotoxic neurotoxin, ibotenic acid, led to an attenuation of hyperalgesia and a reduction of inflammation-induced spinal Fos expression. Furthermore, if the NGC lesion was extended to involve the NRM, the behavioral hyperalgesia and CFA-induced Fos expression were similar to that in vehicle-injected rats. Bilateral LC/SC lesions were produced by microinjections of a noradrenergic neurotoxin, DSP-4. There was a significant increase in inflammation-induced spinal Fos expression, especially in the ipsilateral superficial dorsal horn following LC/SC lesions. These results demonstrated that multiple specific brain stem sites are involved in descending modulation of inflammatory hyperalgesia. Both NRM and LC/SC descending pathways are major sources of enhanced inhibitory modulation in inflamed animals. The persistent hyperalgesia and neuronal hyperexcitability may be mediated in part by a descending pain facilitatory system involving NGC. Thus, the intensity of perceived pain and hyperalgesia is fine-tuned by descending pathways. The imbalance of these modulating systems may be one mechanism underlying variability in acute and chronic pain conditions.

[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.

Semaphorin6A acts as a gate keeper between the central and the peripheral nervous system

PubMed Central

Mauti, Olivier; Domanitskaya, Elena; Andermatt, Irwin; Sadhu, Rejina; Stoeckli, Esther T

2007-01-01

Background During spinal cord development, expression of chicken SEMAPHORIN6A (SEMA6A) is almost exclusively found in the boundary caps at the ventral motor axon exit point and at the dorsal root entry site. The boundary cap cells are derived from a population of late migrating neural crest cells. They form a transient structure at the transition zone between the peripheral nervous system (PNS) and the central nervous system (CNS). Ablation of the boundary cap resulted in emigration of motoneurons from the ventral spinal cord along the ventral roots. Based on its very restricted expression in boundary cap cells, we tested for a role of Sema6A as a gate keeper between the CNS and the PNS. Results Downregulation of Sema6A in boundary cap cells by in ovo RNA interference resulted in motoneurons streaming out of the spinal cord along the ventral roots, and in the failure of dorsal roots to form and segregate properly. PlexinAs interact with class 6 semaphorins and are expressed by both motoneurons and sensory neurons. Knockdown of PlexinA1 reproduced the phenotype seen after loss of Sema6A function both at the ventral motor exit point and at the dorsal root entry site of the lumbosacral spinal cord. Loss of either PlexinA4 or Sema6D function had an effect only at the dorsal root entry site but not at the ventral motor axon exit point. Conclusion Sema6A acts as a gate keeper between the PNS and the CNS both ventrally and dorsally. It is required for the clustering of boundary cap cells at the PNS/CNS interface and, thus, prevents motoneurons from streaming out of the ventral spinal cord. At the dorsal root entry site it organizes the segregation of dorsal roots. PMID:18088409

Spinal curves and health: a systematic critical review of the epidemiological literature dealing with associations between sagittal spinal curves and health.

PubMed

Christensen, Sanne Toftgaard; Hartvigsen, Jan

2008-01-01

The purposes of this study were to (1) determine whether sagittal spinal curves are associated with health in epidemiological studies, (2) estimate the strength of such associations, and (3) consider whether these relations are likely to be causal. A systematic critical literature review of epidemiological (cross-sectional, case-control, cohort) studies published before 2008 including studies identified in the CINAHL, EMBASE, Mantis, and Medline databases was performed using a structured checklist and a quality assessment. Level of evidence analysis was performed as outlined by van Tulder et al (Spine. 2003;28:1290-9), and the strength of associations were determined using the procedure outlined by Hemingway and Marmot (BMJ. 1999;318:1460-7). Quality of the included articles were assessed by our own scoring system based on the STrengthening the Reporting of OBservational studies in Epidemiology checklist. Studies scoring maximum points (4/4 or 3/3) were considered to be of higher quality. Fifty-four original studies were included. We found no strong evidence for any association between sagittal spinal curves and any health outcomes including spinal pain. The included studies were generally of low methodological quality. There is moderate evidence for association between sagittal spinal curves and 4 health outcomes as follows: temporomandibular disorders (no odds ratios [ORs] provided), pelvic organ prolapse (OR, 3.18; 95% confidence interval [CI], 1.46-96.93), daily function (OR range, 1.8-3.7; 95% CI range, 1.1-6.3), and death (OR, 1.40; 95% CI, 1.08-1.91). These associations are however unlikely to be causal. Evidence from epidemiological studies does not support an association between sagittal spinal curves and health including spinal pain. Further research of better methodological quality may affect this conclusion, and causal effects cannot be determined in a systematic review.

Noninvasive Optoelectronic Assessment of Induced Sagittal Imbalance Using the Vicon System.

PubMed

Ould-Slimane, Mourad; Latrobe, Charles; Michelin, Paul; Chastan, Nathalie; Dujardin, Franck; Roussignol, Xavier; Gauthé, Rémi

2017-06-01

Spinal diseases often induce gait disorders with multifactorial origins such as lumbar pain, radicular pain, neurologic complications, or spinal deformities. However, radiography does not permit an analysis of spinal dynamics; therefore, sagittal balance dynamics during gait remain largely unexplored. This prospective and controlled pilot study assessed the Vicon system for detecting sagittal spinopelvic imbalance, to determine the correlations between optoelectronic and radiographic parameters. Reversible anterior sagittal imbalance was induced in 24 healthy men using a thoracolumbar corset. Radiographic, optoelectronic, and comparative analyses were conducted. Corset wearing induced significant variations in radiographic parameters indicative of imbalance; the mean C7-tilt and d/D ratio increased by 15° ± 7.4° and 359%, respectively, whereas the mean spinosacral angle decreased by 16.8° ± 8° (all P < 0.001). The Vicon system detected the imbalance; the mean spinal angle increased by 15.4° ± 5.6° (P < 0.01), the mean floor projection of the C7S1 vector (C7'S1') increased by 126.3 ± 51.9 mm (P < 0.001), and the mean C7-T10-S1 angle decreased by 9.8° ± 3° (P < 0.001). Variations in C7'S1' were significantly correlated with d/D ratio (ρ = 0.58; P < 0.05) and C7-tilt (ρ = 0.636; P < 0.05) variations. Corset wearing induced radiographically confirmed anterior sagittal imbalance detected using the Vicon system. Optoelectronic C7'S1' correlated with radiographic C7-tilt and d/D ratio. Copyright © 2017 Elsevier Inc. All rights reserved.

Cost of Surgery for Symptomatic Spinal Metastases in the United Kingdom.

PubMed

Turner, Isobel; Minhas, Zulfiqar; Kennedy, Joanne; Morris, Stephen; Crockard, Alan; Choi, David

2015-11-01

Spinal metastases represent a significant health and economic burden. The average cost of surgical management varies between institutions and countries, partially a result of differences in health care system billing. This study assessed hospital costs from a single institute in the United Kingdom National Healthcare Service and identified patient factors associated with these costs. This prospective study recruited patients with confirmed symptomatic spinal metastases who presented for surgical treatment. The primary outcome was cost of inpatient treatment collected using the Patient Level Costing and Information System; preoperative details collected included patient demographics, primary tumor type, Tomita and Tokuhashi scores, pain level, EuroQol 5 dimension score, Frankel, Karnofsky, and American Society of Anesthesiologists' physical status classification system scores, and operative details. Costs were analyzed for 74 patients. The mean cost of treatment (standard deviation, SD) per patient was £ 16,885 (£ 10,687); which was mainly comprised of operating theater (25% of the total) and ward costs (27%). Better health status at presentation significantly increased total and ward costs (Frankel score P = 0.006, and EuroQol 5 dimension index P = 0.014 respectively); male sex also increased total and ward costs (P < 0.01 and P = 0.06). Operation cost showed a trend to increased costs with less impairment on American Society of Anesthesiologists' physical status classification system scores. The cost of surgical management of spinal metastases is associated with several factors but is greater in patients presenting with better health status, probably because of their suitability for larger operations, whereas those with poor health status undergo smaller, palliative operations, resulting in shorter inpatient postoperative recovery. Copyright © 2015 Elsevier Inc. All rights reserved.

Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics.

PubMed

Finkel, Richard S; Mercuri, Eugenio; Meyer, Oscar H; Simonds, Anita K; Schroth, Mary K; Graham, Robert J; Kirschner, Janbernd; Iannaccone, Susan T; Crawford, Thomas O; Woods, Simon; Muntoni, Francesco; Wirth, Brunhilde; Montes, Jacqueline; Main, Marion; Mazzone, Elena S; Vitale, Michael; Snyder, Brian; Quijano-Roy, Susana; Bertini, Enrico; Davis, Rebecca Hurst; Qian, Ying; Sejersen, Thomas

2018-03-01

This is the second half of a two-part document updating the standard of care recommendations for spinal muscular atrophy published in 2007. This part includes updated recommendations on pulmonary management and acute care issues, and topics that have emerged in the last few years such as other organ involvement in the severe forms of spinal muscular atrophy and the role of medications. Ethical issues and the choice of palliative versus supportive care are also addressed. These recommendations are becoming increasingly relevant given recent clinical trials and the prospect that commercially available therapies will likely change the survival and natural history of this disease. Copyright © 2017. Published by Elsevier B.V.

Comprehensive management of pressure ulcers in spinal cord injury: Current concepts and future trends

PubMed Central

Kruger, Erwin A.; Pires, Marilyn; Ngann, Yvette; Sterling, Michelle; Rubayi, Salah

2013-01-01

Pressure ulcers in spinal cord injury represent a challenging problem for patients, their caregivers, and their physicians. They often lead to recurrent hospitalizations, multiple surgeries, and potentially devastating complications. They present a significant cost to the healthcare system, they require a multidisciplinary team approach to manage well, and outcomes directly depend on patients' education, prevention, and compliance with conservative and surgical protocols. With so many factors involved in the successful treatment of pressure ulcers, an update on their comprehensive management in spinal cord injury is warranted. Current concepts of local wound care, surgical options, as well as future trends from the latest wound healing research are reviewed to aid medical professionals in treating patients with this difficult problem. PMID:24090179

Crosstalk between p38, Hsp25 and Akt in spinal motor neurons after sciatic nerve injury

NASA Technical Reports Server (NTRS)

Murashov, A. K.; Ul Haq, I.; Hill, C.; Park, E.; Smith, M.; Wang, X.; Wang, X.; Goldberg, D. J.; Wolgemuth, D. J.

2001-01-01

The p38 stress-activated protein kinase pathway is involved in regulation of phosphorylation of Hsp25, which in turn regulates actin filament dynamic in non-neuronal cells. We report that p38, Hsp25 and Akt signaling pathways were specifically activated in spinal motor neurons after sciatic nerve axotomy. The activation of the p38 kinase was required for induction of Hsp25 expression. Furthermore, Hsp25 formed a complex with Akt, a member of PI-3 kinase pathway that prevents neuronal cell death. Together, our observations implicate Hsp25 as a central player in a complex system of signaling that may both promote regeneration of nerve fibers and prevent neuronal cell death in the injured spinal cord.

RAR/RXR and PPAR/RXR Signaling in Spinal Cord Injury

PubMed Central

van Neerven, Sabien; Mey, Jörg

2007-01-01

The retinoid acid receptors (RAR) and peroxisome proliferator-activated receptors (PPAR) have been implicated in the regulation of inflammatory reactions. Both receptor families contain ligand-activated transcription factors which form heterodimers with retinoid X receptors (RXR). We review data that imply RAR/RXR and PPAR/RXR pathways in physiological reactions after spinal cord injury. Experiments show how RAR signaling may improve axonal regeneration and modulate reactions of glia cells. While anti-inflammatory properties of PPAR are well documented in the periphery, their possible roles in the central nervous system have only recently become evident. Due to its anti-inflammatory function this transcription factor family promises to be a useful target after spinal cord or brain lesions. PMID:18060014

Improving the Efficiency and Efficacy of Glibenclamide in Limiting Progressive Hemorrhagic Necrosis Following Traumatic Spinal Cord Injury

DTIC Science & Technology

2014-12-01

functional recovery improved in spinal injured rats using glibenclamide (Glib), an FDA approved anti-diabetic drug that targets SUR1 receptors on... protocols in rat model of SCI. • Established that glibenclamide is neuroprotective across different types of SCI but that efficacy is related to the location...the relative efficacy of glibenclamide with other neuroprotective drugs (Riluzole, systemic hypothermia). Data show that glibenclamide has superior

Repair of Nerve Cell Membrance Damage by Calcium-Dependent, Membrane-Binding Proteins

DTIC Science & Technology

2013-09-01

In acute spinal cord injury the plasma membranes of spinal neurons are torn allowing high concentrations of calcium to enter the cytoplasm, activating...repairing the cell membrane as soon as the increase in intracellular calcium is sensed by calcium -binding proteins. If these repair mechanisms can be...testing the hypothesis that the action of copine, a human calcium -dependent-membrane-binding protein, in model systems can promote a stable repair of

Magnetic Resonance Imaging of the Codman Microsensor Transducer Used for Intraspinal Pressure Monitoring: Findings From the Injured Spinal Cord Pressure Evaluation Study.

PubMed

Phang, Isaac; Mada, Marius; Kolias, Angelos G; Newcombe, Virginia F J; Trivedi, Rikin A; Carpenter, Adrian; Hawkes, Rob C; Papadopoulos, Marios C

2016-05-01

Laboratory and human study. To test the Codman Microsensor Transducer (CMT) in a cervical gel phantom. To test the CMT inserted to monitor intraspinal pressure in a patient with spinal cord injury. We recently introduced the technique of intraspinal pressure monitoring using the CMT to guide management of traumatic spinal cord injury [Werndle et al. Crit Care Med 2014;42:646]. This is analogous to intracranial pressure monitoring to guide management of patients with traumatic brain injury. It is unclear whether magnetic resonance imaging (MRI) of patients with spinal cord injury is safe with the intraspinal pressure CMT in situ. We measured the heating produced by the CMT placed in a gel phantom in various configurations. A 3-T MRI system was used with the body transmit coil and the spine array receive coil. A CMT was then inserted subdurally at the injury site in a patient who had traumatic spinal cord injury and MRI was performed at 1.5 T. In the gel phantom, heating of up to 5°C occurred with the transducer wire placed straight through the magnet bore. The heating was abolished when the CMT wire was coiled and passed away from the bore. We then tested the CMT in a patient with an American Spinal Injuries Association grade C cervical cord injury. The CMT wire was placed in the configuration that abolished heating in the gel phantom. Good-quality T1 and T2 images of the cord were obtained without neurological deterioration. The transducer remained functional after the MRI. Our data suggest that the CMT is MR conditional when used in the spinal configuration in humans. Data from a large patient group are required to confirm these findings. N/A.

Metal levels in corrosion of spinal implants

PubMed Central

Beguiristain, Jose; Duart, Julio

2007-01-01

Corrosion affects spinal instrumentations and may cause local and systemic complications. Diagnosis of corrosion is difficult, and nowadays it is performed almost exclusively by the examination of retrieved instrumentations. We conducted this study to determine whether it is possible to detect corrosion by measuring metal levels on patients with posterior instrumented spinal fusion. Eleven asymptomatic patients, with radiological signs of corrosion of their stainless steel spinal instrumentations, were studied by performing determinations of nickel and chromium in serum and urine. Those levels were compared with the levels of 22 patients with the same kind of instrumentation but without evidence of corrosion and to a control group of 22 volunteers without any metallic implants. Statistical analysis of our results revealed that the patients with spinal implants without radiological signs of corrosion have increased levels of chromium in serum and urine (P < 0.001) compared to volunteers without implants. Corrosion significantly raised metal levels, including nickel and chromium in serum and urine when compared to patients with no radiological signs of corrosion and to volunteers without metallic implants (P < 0.001). Metal levels measured in serum have high sensibility and specificity (area under the ROC curve of 0.981). By combining the levels of nickel and chromium in serum we were able to identify all the cases of corrosion in our series of patients. The results of our study confirm that metal levels in serum and urine are useful in the diagnosis of corrosion of spinal implants and may be helpful in defining the role of corrosion in recently described clinical entities such as late operative site pain or late infection of spinal implants. PMID:17256156

Decreased spinal synaptic inputs to phrenic motor neurons elicit localized inactivity-induced phrenic motor facilitation

PubMed Central

Streeter, K.A.; Baker-Herman, T.L.

2014-01-01

Phrenic motor neurons receive rhythmic synaptic inputs throughout life. Since even brief disruption in phrenic neural activity is detrimental to life, on-going neural activity may play a key role in shaping phrenic motor output. To test the hypothesis that spinal mechanisms sense and respond to reduced phrenic activity, anesthetized, ventilated rats received micro-injections of procaine in the C2 ventrolateral funiculus (VLF) to transiently (~30 min) block axon conduction in bulbospinal axons from medullary respiratory neurons that innervate one phrenic motor pool; during procaine injections, contralateral phrenic neural activity was maintained. Once axon conduction resumed, a prolonged increase in phrenic burst amplitude was observed in the ipsilateral phrenic nerve, demonstrating inactivity-induced phrenic motor facilitation (iPMF). Inhibition of tumor necrosis factor alpha (TNFα) and atypical PKC (aPKC) activity in spinal segments containing the phrenic motor nucleus impaired ipsilateral iPMF, suggesting a key role for spinal TNFα and aPKC in iPMF following unilateral axon conduction block. A small phrenic burst amplitude facilitation was also observed contralateral to axon conduction block, indicating crossed spinal phrenic motor facilitation (csPMF). csPMF was independent of spinal TNFα and aPKC. Ipsilateral iPMF and csPMF following unilateral withdrawal of phrenic synaptic inputs were associated with proportional increases in phrenic responses to chemoreceptor stimulation (hypercapnia), suggesting iPMF and csPMF increase phrenic dynamic range. These data suggest that local, spinal mechanisms sense and respond to reduced synaptic inputs to phrenic motor neurons. We hypothesize that iPMF and csPMF may represent compensatory mechanisms that assure adequate motor output is maintained in a physiological system in which prolonged inactivity ends life. PMID:24681155

Grafting of fetal brainstem 5-HT neurons into the sublesional spinal cord of paraplegic rats restores coordinated hindlimb locomotion.

PubMed

Sławińska, Urszula; Miazga, Krzysztof; Cabaj, Anna M; Leszczyńska, Anna N; Majczyński, Henryk; Nagy, James I; Jordan, Larry M

2013-09-01

In rodent models of spinal cord injury, there is increasing evidence that activation of the locomotor central pattern generator (CPG) below the site of injury with 5-hydroxytryptamine (5-HT) agonists improves locomotor recovery and restores coordination. A promising means of replacing 5-HT control of locomotion is to graft brainstem 5-HT neurons into the spinal cord below the level of the spinal cord injury. However, it is not known whether this approach improves limb coordination because recovery of coordinated stepping has not been documented in detail in previous studies employing this transplantation strategy. Here, adult rats with complete spinal cord transections at the T9/10 level were grafted with E14 fetal neurons from the medulla at the T10/11 vertebra level one month after injury. The B1, B2 and B3 fetal anlagen of brainstem 5-HT neurons, a grouping that included the presumed precursors of recently described 5-HT locomotor command neurons, were used in these grafts. EMG and video recordings of treadmill locomotion evoked by tail stimulation showed full recovery of inter- and intralimb coordination in the grafted rats. We showed, using systemically applied antagonists, that 5-HT₂ and 5-HT₇ receptors mediate the improved locomotion after grafting, but through actions on different populations of spinal locomotor neurons. Specifically, 5-HT₂ receptors control CPG activation as well as motoneuron output, while 5-HT₇ receptors contribute primarily to activity of the locomotor CPG. These results are consistent with the roles for these receptors during locomotion in intact rodents and in rodent brainstem-spinal cord in vitro preparations. Copyright © 2013 Elsevier Inc. All rights reserved.

Sensory processing of deep tissue nociception in the rat spinal cord and thalamic ventrobasal complex.

PubMed

Sikandar, Shafaq; West, Steven J; McMahon, Stephen B; Bennett, David L; Dickenson, Anthony H

2017-07-01

Sensory processing of deep somatic tissue constitutes an important component of the nociceptive system, yet associated central processing pathways remain poorly understood. Here, we provide a novel electrophysiological characterization and immunohistochemical analysis of neural activation in the lateral spinal nucleus (LSN). These neurons show evoked activity to deep, but not cutaneous, stimulation. The evoked responses of neurons in the LSN can be sensitized to somatosensory stimulation following intramuscular hypertonic saline, an acute model of muscle pain, suggesting this is an important spinal relay site for the processing of deep tissue nociceptive inputs. Neurons of the thalamic ventrobasal complex (VBC) mediate both cutaneous and deep tissue sensory processing, but in contrast to the lateral spinal nucleus our electrophysiological studies do not suggest the existence of a subgroup of cells that selectively process deep tissue inputs. The sensitization of polymodal and thermospecific VBC neurons to mechanical somatosensory stimulation following acute muscle stimulation with hypertonic saline suggests differential roles of thalamic subpopulations in mediating cutaneous and deep tissue nociception in pathological states. Overall, our studies at both the spinal (lateral spinal nucleus) and supraspinal (thalamic ventrobasal complex) levels suggest a convergence of cutaneous and deep somatosensory inputs onto spinothalamic pathways, which are unmasked by activation of muscle nociceptive afferents to produce consequent phenotypic alterations in spinal and thalamic neural coding of somatosensory stimulation. A better understanding of the sensory pathways involved in deep tissue nociception, as well as the degree of labeled line and convergent pathways for cutaneous and deep somatosensory inputs, is fundamental to developing targeted analgesic therapies for deep pain syndromes. © 2017 University College London. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Neuro-Magnetic Resonance Imaging in Hand, Foot, and Mouth Disease: Finding in 412 Patients and Prognostic Features.

PubMed

Lian, Zhou-Yang; Li, He-Hong; Zhang, Bin; Dong, Yu-Hao; Deng, Wu-Xu; Liu, Jing; Luo, Xiao-Ning; Huang, Biao; Liang, Chang-Hong; Zhang, Shui-Xing

The aims of this study were to describe the neuroimaging findings in hand, foot, and mouth disease and determine those who may provide prognosis. Magnetic resonance imaging scans in 412 severe hand, foot, and mouth disease between 2009 and 2014 were retrospectively evaluated. The patients who had the neurological signs were followed for 6 months to 1 year. According to the good or poor prognosis, 2 groups were categorized. The incidence of lesions in different sites between the 2 groups was compared, and multivariate analysis was used to look for risk factors. The major sites of involvement for all patients with percentages were the medulla oblongata (16.1%), spinal anterior nerve roots (12.4%), thoracic segments (11.1%), brain or spinal meninges (8.3%), and so on. There were 347 patients (84.2%) with good prognosis and 65 (15.8%) with poor prognosis in the follow-up. There was a significantly higher rate of lesions involving the cerebral white substance, thalamus, medulla oblongata, pons, midbrain, and spinal cord in the group with poor prognosis. Multivariate analysis showed 2 independent risk factors associated with poor prognosis: lesions located in the medulla oblongata (P < 0.015) and spinal cord (P < 0.001) on magnetic resonance imaging; the latter was the most significant prognostic factor (odds ratio, 29.11; P < 0.001). We found that the distribution patterns for all patients mainly involved the medulla oblongata, spinal anterior nerve roots, thoracic segments, and brain or spinal meninges. Our findings suggested that patients with lesions located in the medulla oblongata and spinal cord may be closely monitored for early intervention and meticulous management. For children with the symptom of nervous system, they are strongly recommended for magnetic resonance examination.

Nonreciprocal mechanisms in up- and downregulation of spinal motoneuron excitability by modulators of KCNQ/Kv7 channels.

PubMed

Lombardo, Joseph; Harrington, Melissa A

2016-11-01

KCNQ/K v 7 channels form a slow noninactivating K + current, also known as the M current. They activate in the subthreshold range of membrane potentials and regulate different aspects of excitability in neurons of the central nervous system. In spinal motoneurons (MNs), KCNQ/K v 7 channels have been identified in the somata, axonal initial segment, and nodes of Ranvier, where they generate a slow, noninactivating, K + current sensitive to both muscarinic receptor-mediated inhibition and KCNQ/K v 7 channel blockers. In this study, we thoroughly reevaluated the function of up- and downregulation of KCNQ/K v 7 channels in mouse immature spinal MNs. Using electrophysiological techniques together with specific pharmacological modulators of the activity of KCNQ/K v 7 channels, we show that enhancement of the activity of these channels decreases the excitability of spinal MNs in mouse neonates. This action on MNs results from a combination of hyperpolarization of the resting membrane potential, a decrease in the input resistance, and depolarization of the voltage threshold. On the other hand, the effect of inhibition of KCNQ/K v 7 channels suggested that these channels play a limited role in regulating basal excitability. Computer simulations confirmed that pharmacological enhancement of KCNQ/K v 7 channel activity decreases excitability and also suggested that the effects of inhibition of KCNQ/K v 7 channels on the excitability of spinal MNs do not depend on a direct effect in these neurons but likely on spinal cord synaptic partners. These results indicate that KCNQ/K v 7 channels have a fundamental role in the modulation of the excitability of spinal MNs acting both in these neurons and in their local presynaptic partners. Copyright © 2016 the American Physiological Society.

Nonreciprocal mechanisms in up- and downregulation of spinal motoneuron excitability by modulators of KCNQ/Kv7 channels

PubMed Central

Lombardo, Joseph

2016-01-01

KCNQ/Kv7 channels form a slow noninactivating K+ current, also known as the M current. They activate in the subthreshold range of membrane potentials and regulate different aspects of excitability in neurons of the central nervous system. In spinal motoneurons (MNs), KCNQ/Kv7 channels have been identified in the somata, axonal initial segment, and nodes of Ranvier, where they generate a slow, noninactivating, K+ current sensitive to both muscarinic receptor-mediated inhibition and KCNQ/Kv7 channel blockers. In this study, we thoroughly reevaluated the function of up- and downregulation of KCNQ/Kv7 channels in mouse immature spinal MNs. Using electrophysiological techniques together with specific pharmacological modulators of the activity of KCNQ/Kv7 channels, we show that enhancement of the activity of these channels decreases the excitability of spinal MNs in mouse neonates. This action on MNs results from a combination of hyperpolarization of the resting membrane potential, a decrease in the input resistance, and depolarization of the voltage threshold. On the other hand, the effect of inhibition of KCNQ/Kv7 channels suggested that these channels play a limited role in regulating basal excitability. Computer simulations confirmed that pharmacological enhancement of KCNQ/Kv7 channel activity decreases excitability and also suggested that the effects of inhibition of KCNQ/Kv7 channels on the excitability of spinal MNs do not depend on a direct effect in these neurons but likely on spinal cord synaptic partners. These results indicate that KCNQ/Kv7 channels have a fundamental role in the modulation of the excitability of spinal MNs acting both in these neurons and in their local presynaptic partners. PMID:27512022

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

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

PubMed Central

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

2011-01-01

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

[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.

Do Not Resonate with Actions: Sentence Polarity Modulates Cortico-Spinal Excitability during Action-Related Sentence Reading

PubMed Central

Liuzza, Marco Tullio; Candidi, Matteo; Aglioti, Salvatore Maria

2011-01-01

Background Theories of embodied language suggest that the motor system is differentially called into action when processing motor-related versus abstract content words or sentences. It has been recently shown that processing negative polarity action-related sentences modulates neural activity of premotor and motor cortices. Methods and Findings We sought to determine whether reading negative polarity sentences brought about differential modulation of cortico-spinal motor excitability depending on processing hand-action related or abstract sentences. Facilitatory paired-pulses Transcranial Magnetic Stimulation (pp-TMS) was applied to the primary motor representation of the right-hand and the recorded amplitude of induced motor-evoked potentials (MEP) was used to index M1 activity during passive reading of either hand-action related or abstract content sentences presented in both negative and affirmative polarity. Results showed that the cortico-spinal excitability was affected by sentence polarity only in the hand-action related condition. Indeed, in keeping with previous TMS studies, reading positive polarity, hand action-related sentences suppressed cortico-spinal reactivity. This effect was absent when reading hand action-related negative polarity sentences. Moreover, no modulation of cortico-spinal reactivity was associated with either negative or positive polarity abstract sentences. Conclusions Our results indicate that grammatical cues prompting motor negation reduce the cortico-spinal suppression associated with affirmative action sentences reading and thus suggest that motor simulative processes underlying the embodiment may involve even syntactic features of language. PMID:21347305

Ultraclean air for prevention of postoperative infection after posterior spinal fusion with instrumentation: a comparison between surgeries performed with and without a vertical exponential filtered air-flow system.

PubMed

Gruenberg, Marcelo F; Campaner, Gustavo L; Sola, Carlos A; Ortolan, Eligio G

2004-10-15

This study retrospectively compared infection rates between adult patients after posterior spinal instrumentation procedures performed in a conventional versus an ultraclean air operating room. To evaluate if the use of ultraclean air technology could decrease the infection rate after posterior spinal arthrodesis with instrumentation. Postoperative wound infection after posterior arthrodesis remains a feared complication in spinal surgery. Although this frequent complication results in a significant problem, the employment of ultraclean air technology, as it is commonly used for arthroplasty, has not been reported as a possible alternative to reduce the infection rate after complex spine surgery. One hundred seventy-nine patients having posterior spinal fusion with instrumentation were divided into 2 groups: group I included 139 patients operated in a conventional operating room, and group II included 40 patients operated in a vertical laminar flow operating room. Patient selection was performed favoring ultraclean air technology for elective cases in which high infection risk was considered. A statistical analysis of the infection rate and its associated risk factors between both groups was assessed. We observed 18 wound infections in group I and 0 in group II. Comparison of infection rates using the chi-squared test showed a statistically significant difference (P <0.017). The use of ultraclean air technology reduced the infection rate after complex spinal procedures and appears to be an interesting alternative that still needs to be prospectively studied with a randomized protocol.

Towards a miniaturized brain-machine-spinal cord interface (BMSI) for restoration of function after spinal cord injury.

PubMed

Shahdoost, Shahab; Frost, Shawn; Van Acker, Gustaf; DeJong, Stacey; Dunham, Caleb; Barbay, Scott; Nudo, Randolph; Mohseni, Pedram

2014-01-01

Nearly 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress towards developing a miniaturized brain-machine-spinal cord interface (BMSI) that is envisioned to convert in real time the neural command signals recorded from the brain to electrical stimuli delivered to the spinal cord below the injury level. Specifically, the paper reports on a corticospinal interface integrated circuit (IC) as a core building block for such a BMSI that is capable of low-noise recording of extracellular neural spikes from the cerebral cortex as well as muscle activation using intraspinal microstimulation (ISMS) in a rat with contusion injury to the thoracic spinal cord. The paper further presents results from a neurobiological study conducted in both normal and SCI rats to investigate the effect of various ISMS parameters on movement thresholds in the rat hindlimb. Coupled with proper signal-processing algorithms in the future for the transformation between the cortically recorded data and ISMS parameters, such a BMSI has the potential to facilitate functional recovery after an SCI by re-establishing corticospinal communication channels lost due to the injury.

Posterior Vertebral Column Resection for Severe and Rigid Spinal Deformity Associated With Neurological Deficit After Implant Removal Following Posterior Instrumented Fusion: A Case Report and Literature Review.

PubMed

Tao, Youping; Wu, Jigong; Ma, Huasong; Zhang, Lele; Shao, Shuilin; Si, Zebing; Gao, Bo; Ji, Yong; Li, Haixia; Tao, Feifei

2015-07-01

Case report. To investigate the safety and efficacy of posterior vertebral column resection for severe and rigid spinal deformity associated with neurological deficit after implant removal following posterior instrumented fusion. Loss of correction after implant removal in patients with posterior instrumented fusion has been previously reported. However, to our knowledge, posterior vertebral column resection (PVCR) for severe and rigid spinal deformity associated with neurological deficit after implant removal following posterior instrumented fusion has not been reported. An 18-year-old female with severe and rigid spinal deformity associated with neurological deficit was classified as Frankel C, according to the Frankel grading system. She underwent posterior spinal fusion with pedicle screw fixation at 16 years, and her implants were removed after 1 year due to back pain. Seven months after removal of the implants, she began to experience weakness in her lower limbs but did not seek any treatment. She was unable to stand and had to use a wheelchair. The patient successfully underwent PVCR and posterior reinstrumentation. Within 3 months, her neurological status improved to Frankel E. The patient had no neurological deterioration and infections. There was no instrumentation failure and loosening correction at the 32 months follow-up. Our results suggest that PVCR and pedicle screw fixation is a safe and efficacious option for severe and rigid spinal deformity associated with neurological deficit after implant removal following posterior instrumented fusion. N/A.

Imbalance in Multiple Sclerosis: A Result of Slowed Spinal Somatosensory Conduction

PubMed Central

Cameron, Michelle H.; Horak, Fay B.; Herndon, Robert R.; Bourdette, Dennis

2009-01-01

Balance problems and falls are common in people with multiple sclerosis (MS) but their cause and nature are not well understood. It is known that MS affects many areas of the central nervous system that can impact postural responses to maintain balance, including the cerebellum and the spinal cord. Cerebellar balance disorders are associated with normal latencies but reduced scaling of postural responses. We therefore examined the latency and scaling of automatic postural responses, and their relationship to somatosensory evoked potentials (SSEPs), in 10 people with MS and imbalance and 10 age-, sex-matched, healthy controls. The latency and scaling of postural responses to backward surface translations of 5 different velocities and amplitudes, and the latency of spinal and supraspinal somatosensory conduction, were examined. Subjects with MS had large, but very delayed automatic postural response latencies compared to controls (161ms ± 31 vs 102 ± 21, p < 0.01) and these postural response latencies correlated with the latencies of their spinal SSEPs (r=0.73, p< 0.01). Subjects with MS also had normal or excessive scaling of postural response amplitude to perturbation velocity and amplitude. Longer latency postural responses were associated with less velocity scaling and more amplitude scaling. Balance deficits in people with MS appear to be caused by slowed spinal somatosensory conduction and not by cerebellar involvement. People with MS appear to compensate for their slowed spinal somatosensory conduction by increasing the amplitude scaling and the magnitude of their postural responses. PMID:18570015

Hospitalization for partial nephrectomy was not associated with intrathecal opioid analgesia: Retrospective analysis.

PubMed

Weingarten, Toby N; Del Mundo, Serena B; Yeoh, Tze Yeng; Scavonetto, Federica; Leibovich, Bradley C; Sprung, Juraj

2014-10-01

The aim of this retrospective study is to test the hypothesis that the use of spinal analgesia shortens the length of hospital stay after partial nephrectomy. We reviewed all patients undergoing partial nephrectomy for malignancy through flank incision between January 1, 2008, and June 30, 2011. We excluded patients who underwent tumor thrombectomy, used sustained-release opioids, or had general anesthesia supplemented by epidural analgesia. Patients were grouped into "spinal" (intrathecal opioid injection for postoperative analgesia) versus "general anesthetic" group, and "early" discharge group (within 3 postoperative days) versus "late" group. Association between demographics, patient physical status, anesthetic techniques, and surgical complexity and hospital stay were analyzed using multivariable logistic regression analysis. Of 380 patients, 158 (41.6%) were discharged "early" and 151 (39.7%) were "spinal" cases. Both spinal and early discharge groups had better postoperative pain control and used less postoperative systemic opioids. Spinal analgesia was associated with early hospital discharge, odds ratio 1.52, (95% confidence interval 1.00-2.30), P = 0.05, but in adjusted analysis was no longer associated with early discharge, 1.16 (0.73-1.86), P = 0.52. Early discharge was associated with calendar year, with more recent years being associated with early discharge. Spinal analgesia combined with general anesthesia was associated with improved postoperative pain control during the 1(st) postoperative day, but not with shorter hospital stay following partial nephrectomy. Therefore, unaccounted practice changes that occurred during more recent times affected hospital stay.

The association of socio-economic factors with physical fitness and activity behaviours, spinal posture and retinal vessel parameters in first graders in urban Switzerland.

PubMed

Imhof, Katharina; Faude, Oliver; Donath, Lars; Bean-Eisenhut, Salome; Hanssen, Henner; Zahner, Lukas

2016-01-01

Socio-economic status during childhood has been shown to be a strong predictor of adult health outcome. Therefore, we examined associations of parental educational level, household income and migrant background with physical fitness, spinal flexibility, spinal posture as well as retinal vessel diameters in children of an urban Swiss region. A total of 358 first graders of the Swiss canton Basel-Stadt (age: 7.3, SD: 0.4) were examined. Physical fitness (20 m shuttle run test, 20 m sprint, jumping sidewards and balancing backwards), spinal flexibility and spinal posture (MediMouse®, Idiag, Fehraltdorf, Switzerland) and retinal microcirculation (Static Retinal Vessel Analyzer, Imedos Systems UG, Jena, Germany) were assessed. Parental education, household income, migrant background and activity behaviour were evaluated with a questionnaire. Parental education was associated with child aerobic fitness (P = 0.03) and screen time (P < 0.001). Household income was associated with jumping sidewards (P = 0.009), balancing backwards (P = 0.03) and sports club participation (P = 0.02). Migrant background was associated with BMI (P = 0.001), body fat (P = 0.03), aerobic fitness (P = 0.007), time spent playing outdoors (P < 0.001) and screen time (P < 0.001). For spinal flexibility and retinal vessel diameter, no associations were found (0.06 < P < 0.8). Low parental education, low household income and a migrant background are associated with poor physical fitness, higher BMI and body fat percentage and low-activity behaviour.

Intratumoral hemorrhage because of primary spinal mixed germ cell tumor presenting with atypical radiological features in an adult.

PubMed

Yamamoto, Junkoh; Takahashi, Mayu; Nakano, Yoshiteru; Saito, Takeshi; Kitagawa, Takehiro; Ueta, Kunihiro; Miyaoka, Ryo; Nakamura, Eiichiro; Nishizawa, Shigeru

2013-10-01

Germ cell tumors are known to arise in the central nervous system, usually in the intracranial regions. However, primary spinal mixed germ cell tumors are extremely rare. This is the first reported case of intratumoral hemorrhage because of a primary spinal mixed germ cell tumor consisting of germinoma and immature teratoma in the conus medullaris of an adult patient that presented with rapid changes on magnetic resonance image (MRI). We report this rare case and discuss the clinical manifestations of an intramedullary spinal mixed germ cell tumor in adult. A case report. A 42-year-old woman experienced buttock numbness, and a spinal cord tumor was observed on the conus medullaris on MRI. The patient was scheduled for an operation in 1 month, but she developed sudden-onset neurologic deterioration. Rapid progression of the tumor was observed on follow-up MRI. The tumor was removed by emergency surgery and was identified as a primary mixed germinoma and immature teratoma. The patient received adjuvant chemotherapy and radiotherapy after gross total resection. The neurologic deficit of the patient was relieved, and recurrence of the tumor was not observed 26 months after the surgery. We present this rare case and emphasize the necessity of precise diagnosis and early treatment of primary spinal germ cell tumor. Close observation on MRI is required after surgery, and adjuvant chemotherapy and radiotherapy should be considered according to the pathologic features. Copyright © 2013 Elsevier Inc. All rights reserved.

Laparoscopic cholecystectomy under segmental thoracic spinal anaesthesia: a feasibility study.

PubMed

van Zundert, A A J; Stultiens, G; Jakimowicz, J J; Peek, D; van der Ham, W G J M; Korsten, H H M; Wildsmith, J A W

2007-05-01

Laparoscopic surgery is normally performed under general anaesthesia, but regional techniques have been found beneficial, usually in the management of patients with major medical problems. Encouraged by such experience, we performed a feasibility study of segmental spinal anaesthesia in healthy patients. Twenty ASA I or II patients undergoing elective laparoscopic cholecystectomy received a segmental (T10 injection) spinal anaesthetic using 1 ml of bupivacaine 5 mg ml-1 mixed with 0.5 ml of sufentanil 5 microg ml-1. Other drugs were only given (systemically) to manage patient anxiety, pain, nausea, hypotension, or pruritus during or after surgery. The patients were reviewed 3 days postoperatively by telephone. The spinal anaesthetic was performed easily in all patients, although one complained of paraesthesiae which responded to slight needle withdrawal. The block was effective for surgery in all 20 patients, six experiencing some discomfort which was readily treated with small doses of fentanyl, but none requiring conversion to general anaesthesia. Two patients required midazolam for anxiety and two ephedrine for hypotension. Recovery was uneventful and without sequelae, only three patients (all for surgical reasons) not being discharged home on the day of operation. This preliminary study has shown that segmental spinal anaesthesia can be used successfully and effectively for laparoscopic surgery in healthy patients. However, the use of an anaesthetic technique involving needle insertion into the vertebral canal above the level of termination of the spinal cord requires great caution and should be restricted in application until much larger numbers of patients have been studied.

Spinal anesthesia: an evergreen technique.

PubMed

Di Cianni, Simone; Rossi, Maria; Casati, Andrea; Cocco, Caterina; Fanelli, Guido

2008-04-01

Spinal anesthesia is a simple technique that provides a deep and fast surgical block through the injection of small doses of local anesthetic solution into the subarachnoid space. The purpose of this review is to provide an overview on recent developments on local anesthetic drugs, side effects, and special techniques of intrathecal anesthesia. Spinal anesthesia can be considered adequately safe, and severe complications are reasonably rare. The cardiovascular effects associated with sympathetic block are more frequent, but successfully treated with volume expansion and administration of vasoactive drugs. It is clear that the total dose of local anesthetic injected into the subarachnoid space is the most important determinant of both therapeutic and unwanted effects of spinal anesthesia. Several studies have also demonstrated the efficacy and safety of using small doses of long acting agents, such as bupivacaine or ropivacaine, to produce an adequately short spinal block in outpatients. Levopivacaine, the pure S(-)-enantiomer of racemic bupivacaine showed a lower risk of cardiovascular and central nervous system (CNS) toxicity than bupivacaine. In the last years we have assisted important changes in the health care organization, with most of the surgical procedures performed on outpatients or on elderly patients with concomitant diseases. This forced us to change the indications and clinical use of intrathecal anesthesia techniques, which have been modified according to the changing needs of surgery. The development of new drugs and special techniques for spinal anesthesia will further improve the clinical use of this old but evergreen technique.

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.

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.

[The Role of Imaging in Central Nervous System Infections].

PubMed

Yokota, Hajime; Tazoe, Jun; Yamada, Kei

2015-07-01

Many infections invade the central nervous system. Magnetic resonance imaging (MRI) is the main tool that is used to evaluate infectious lesions of the central nervous system. The useful sequences on MRI are dependent on the locations, such as intra-axial, extra-axial, and spinal cord. For intra-axial lesions, besides the fundamental sequences, including T1-weighted images, T2-weighted images, and fluid-attenuated inversion recovery (FLAIR) images, advanced sequences, such as diffusion-weighted imaging, diffusion tensor imaging, susceptibility-weighted imaging, and MR spectroscopy, can be applied. They are occasionally used as determinants for quick and correct diagnosis. For extra-axial lesions, understanding the differences among 2D-conventional T1-weighted images, 2D-fat-saturated T1-weighted images, 3D-Spin echo sequences, and 3D-Gradient echo sequence after the administration of gadolinium is required to avoid wrong interpretations. FLAIR plus gadolinium is a useful tool for revealing abnormal enhancement on the brain surface. For the spinal cord, the sequences are limited. Evaluating the distribution and time course of the spinal cord are essential for correct diagnoses. We summarize the role of imaging in central nervous system infections and show the pitfalls, key points, and latest information in them on clinical practices.

Investigations of the Effects of Altered Vestibular System Function on Hindlimb Anti-Gravity Muscles

NASA Technical Reports Server (NTRS)

Lowery, Mary Sue

1998-01-01

Exposure to different gravitational environments, both the microgravity of spaceflight and the hypergravity of centrifugation, result in altered vestibulo-spinal function which can be reversed by reacclimation to earth gravity (2). Control of orientation, posture, and locomotion are functions of the vestibular system which are altered by changes in gravitational environment. Not only is the vestibular system involved with coordination and proprioception, but the gravity sensing portion of the vestibular system also plays a major role in maintaining muscle tone through projections to spinal cord motoneurons that control anti-gravity muscles. I have been involved with investigations of several aspects of the link between vestibular inputs and muscle morphology and function during my work with Dr. Nancy Daunton this summer and the previous summer. We have prepared a manuscript for submission (4) to Aviation, Space, and Environmental Medicine based on work that I performed last summer in Dr. Daunton's lab. Techniques developed for that project will be utilized in subsequent experiments begun in the summer of 1998. I have been involved with the development of a pilot project to test the effects of vestibular galvanic stimulation (VGS) on anti-gravity muscles and in another project testing the effects of the ototoxic drug streptomycin on the otolith-spinal reflex and anti-gravity muscle morphology.

Tramadol and Tramadol+Caffeine Synergism in the Rat Formalin Test Are Mediated by Central Opioid and Serotonergic Mechanisms

PubMed Central

Carrillo-Munguía, Norma; González-Trujano, Ma. Eva; Huerta, Miguel; Trujillo, Xochitl; Díaz-Reval, M. Irene

2015-01-01

Different analgesic combinations with caffeine have shown this drug to be capable of increasing the analgesic effect. Many combinations with nonsteroidal anti-inflammatory drugs (NSAIDs) have been carried out, but, in regard to opioids, only combinations with morphine and tramadol have been reported. The antinociceptive synergism mechanism of these combinations is not well understood. The purpose of the present study was to determine the participation of spinal and supraspinal opioidergic and serotonergic systems in the synergic effect of the tramadol+caffeine combination in the rat formalin test. At the supraspinal level, the opioid antagonist, naloxone, completely reversed the effect of the drug combination, whereas ketanserin, a 5-HT2 receptor antagonist, inhibited the effect by 60%; however, ondansetron, a 5-HT3 receptor antagonist, did not alter the combination effect. When the antagonists were intrathecally administered, there was a significant reduction in all tramadol-caffeine combination effects. With respect to tramadol alone, there was significant participation of the opioid system at the supraspinal level, whereas it was the serotonergic system that participated at the spinal level by means of the two receptors studied. In conclusion, the tramadol+caffeine combination synergically activated the opioid and serotonergic systems at the supraspinal level, as well as at the spinal level, to produce the antinociception. PMID:26146627

Assessment of an updated double-vasopressor automated system using Nexfin for the maintenance of haemodynamic stability to improve peri-operative outcome during spinal anaesthesia for caesarean section.

PubMed

Sng, B L; Wang, H; Assam, P N; Sia, A T

2015-06-01

Hypotension occurs commonly during spinal anaesthesia for caesarean section, associated with maternal and fetal adverse effects. We developed a double-vasopressor automated system with a two-step algorithm and continuous non-invasive haemodynamic monitoring using the Nexfin device. The system delivered 25 μg phenylephrine every 30 s when systolic blood pressure was between 90% and 100% of baseline, or 2 mg ephedrine at this blood pressure range and heart rate < 60 beats.min(-1) ; and 50 μg phenylephrine or 4 mg ephedrine when systolic blood pressure was < 90% of baseline with the same heart rate criterion. Fifty-seven women received standardised spinal anaesthesia. Twenty-seven (47.4%) had at least one reading of hypotension defined as systolic blood pressure < 80% baseline. Systolic blood pressure was within 20% of the baseline in a mean (SD) of 79.8 (20.9)% of measurements. Fifty-three (93.0%) women required phenylephrine before delivery while 10 (17.5%) required ephedrine. Six women (10.5%) experienced nausea and three (5.3%) vomited. The system was able to achieve a low incidence of maternal hypotension with good maternal and fetal outcomes. © 2015 The Association of Anaesthetists of Great Britain and Ireland.

Spine Stereotactic Body Radiotherapy: Indications, Outcomes, and Points of Caution

PubMed Central

Eppinga, Wietse; Charest-Morin, Raphaele; Soliman, Hany; Myrehaug, Sten; Maralani, Pejman Jabehdar; Campbell, Mikki; Lee, Young K.; Fisher, Charles; Fehlings, Michael G.; Chang, Eric L.; Lo, Simon S.; Sahgal, Arjun

2017-01-01

Study Design: A broad narrative review. Objectives: The objective of this article is to provide a technical review of spine stereotactic body radiotherapy (SBRT) planning and delivery, indications for treatment, outcomes, complications, and the challenges of response assessment. The surgical approach to spinal metastases is discussed with an overview of emerging minimally invasive techniques. Methods: A comprehensive review of the literature was conducted on the techniques, outcomes, and developments in SBRT and surgery for spinal metastases. Results: The optimal management of patients with spinal metastases is complex and requires multidisciplinary assessment from an oncologic team that is familiar with the shifting paradigm as a consequence of evolving techniques in surgery and stereotactic radiation, as well as new developments in systemic agents. The Spinal Instability Neoplastic Score and the epidural spinal cord compression (Bilsky) grading system are useful tools that facilitate communication among oncologic team members and can direct management by providing a baseline assessment of risks prior to therapy. The combined multimodality approach with “separation surgery” followed by postoperative spine SBRT achieves thecal sac decompression, improves tumor control, and avoids complications that may be associated with more extensive surgery. Conclusion: Spine SBRT is a highly effective treatment that is capable of delivering ablative doses to the target while sparing the critical organs-at-risk, chiefly the critical neural tissues, within a short and manageable schedule. At the same time, surgery occupies an important role in select patients, particularly with the expanding availability and expertise in minimally invasive techniques. With rapid adoption of spine SBRT in centers outside of the academic setting, it is imperative for the practicing oncologist to understand the relevance and application of these evolving concepts. PMID:28507888

Electrospun fiber surface nanotopography influences astrocyte-mediated neurite outgrowth.

PubMed

Johnson, Christopher D; D'Amato, Anthony R; Puhl, Devan L; Wich, Douglas M; Vespermann, Amanda; Gilbert, Ryan J

2018-05-15

Aligned, electrospun fiber scaffolds provide topographical guidance for regenerating neurons and glia after central nervous system injury. To date, no study has explored how fiber surface nanotopography affects astrocyte response to fibrous scaffolds. Astrocytes play important roles in the glial scar, the blood brain barrier, and in maintaining homeostasis in the central nervous system. In this study, electrospun poly L-lactic acid fibers were engineered with smooth, pitted, or divoted surface nanotopography. Cortical or spinal cord primary rat astrocytes were cultured on the surfaces for either 1 or 3 days to examine the astrocyte response over time. The results showed that cortical astrocytes were significantly shorter and broader on the pitted and divoted fibers compared to those on smooth fibers. However, spinal cord astrocyte morphology was not significantly altered by the surface features. These findings indicate that astrocytes from unique anatomical locations respond differently to the presence of nanotopography. Western Blot results show that the differences in morphology were not associated with significant changes in GFAP or vinculin in either astrocyte population, suggesting that surface pits and divots do not induce a reactive phenotype in either cortical or spinal cord astrocytes. Finally, astrocytes were co-cultured with dorsal root ganglia to determine how the surfaces affected astrocyte-mediated neurite outgrowth. Astrocytes cultured on the fibers for shorter periods of time (1 day) generally supported longer neurite outgrowth. Pitted and divoted fibers restricted spinal cord astrocyte-mediated neurite outgrowth, while smooth fibers increased 3 day spinal cord astrocyte-mediated neurite outgrowth. In total, fiber surface nanotopography can influence astrocyte elongation and influence the capability of astrocytes to direct neurites. Therefore, fiber surface characteristics should be carefully controlled to optimize astrocyte-mediated axonal regeneration. . © 2018 IOP Publishing Ltd.

Apoptosis and proliferation of oligodendrocyte progenitor cells in the irradiated rodent spinal cord

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

Atkinson, Shelley L.; Li Yuqing; Wong, C. Shun

2005-06-01

Purpose: Oligodendrocytes undergo early apoptosis after irradiation. The aim of this study was to determine the relationship between oligodendroglial apoptosis and proliferation of oligodendrocyte progenitor cells (OPC) in the irradiated central nervous system. Methods and Materials: Adult rats and p53 transgenic mice were given single doses of 2 Gy, 8 Gy, or 22 Gy to the cervical spinal cord. Apoptosis was assessed using TUNEL (Tdt-mediated dUTP terminal nick-end labeling) staining or by examining nuclear morphology. Oligodendrocyte progenitor cells were identified with an NG2 antibody or by in situ hybridization for platelet-derived growth factor receptor {alpha}. Proliferation of OPC was assessedmore » by in vivo bromodeoxyuridine (BrdU) labeling and subsequent immunohistochemistry. Because radiation-induced apoptosis of oligodendroglial cells is p53 dependent, p53 transgenic mice were used to study the relationship between apoptosis and cell proliferation. Results: Oligodendrocyte progenitor cells underwent apoptosis within 24 h of irradiation in the rat. That did not result in a change in OPC density at 24 h. Oligodendrocyte progenitor cell density was significantly reduced by 2-4 weeks, but showed recovery by 6 weeks after irradiation. An increase in BrdU-labeled cells was observed at 2 weeks after 8 Gy or 22 Gy, and proliferating cells in the rat spinal cord were immunoreactive for NG2. The mouse spinal cord showed a similar early cell proliferation after irradiation. No difference was observed in the proliferation response in the spinal cord of p53 -/- mice compared with wild type animals. Conclusions: Oligodendroglial cells undergo early apoptosis and OPC undergo early proliferation after ionizing radiation. However, apoptosis is not likely to be the trigger for early proliferation of OPC in the irradiated central nervous system.« less

Subdural Thoracolumbar Spine Hematoma after Spinal Anesthesia: A Rare Occurrence and Literature Review of Spinal Hematomas after Spinal Anesthesia.

PubMed

Maddali, Prasanthi; Walker, Blake; Fisahn, Christian; Page, Jeni; Diaz, Vicki; Zwillman, Michael E; Oskouian, Rod J; Tubbs, R Shane; Moisi, Marc

2017-02-16

Spinal hematomas are a rare but serious complication of spinal epidural anesthesia and are typically seen in the epidural space; however, they have been documented in the subdural space. Spinal subdural hematomas likely exist within a traumatically induced space within the dural border cell layer, rather than an anatomical subdural space. Spinal subdural hematomas present a dangerous clinical situation as they have the potential to cause significant compression of neural elements and can be easily mistaken for spinal epidural hematomas. Ultrasound can be an effective modality to diagnose subdural hematoma when no epidural blood is visualized. We have reviewed the literature and present a full literature review and a case presentation of an 82-year-old male who developed a thoracolumbar spinal subdural hematoma after spinal epidural anesthesia. Anticoagulant therapy is an important predisposing risk factor for spinal epidural hematomas and likely also predispose to spinal subdural hematomas. It is important to consider spinal subdural hematomas in addition to spinal epidural hematomas in patients who develop weakness after spinal epidural anesthesia, especially in patients who have received anticoagulation.

Reliability analysis of the AOSpine thoracolumbar spine injury classification system by a worldwide group of naïve spinal surgeons.

PubMed

Kepler, Christopher K; Vaccaro, Alexander R; Koerner, John D; Dvorak, Marcel F; Kandziora, Frank; Rajasekaran, Shanmuganathan; Aarabi, Bizhan; Vialle, Luiz R; Fehlings, Michael G; Schroeder, Gregory D; Reinhold, Maximilian; Schnake, Klaus John; Bellabarba, Carlo; Cumhur Öner, F

2016-04-01

The aims of this study were (1) to demonstrate the AOSpine thoracolumbar spine injury classification system can be reliably applied by an international group of surgeons and (2) to delineate those injury types which are difficult for spine surgeons to classify reliably. A previously described classification system of thoracolumbar injuries which consists of a morphologic classification of the fracture, a grading system for the neurologic status and relevant patient-specific modifiers was applied to 25 cases by 100 spinal surgeons from across the world twice independently, in grading sessions 1 month apart. The results were analyzed for classification reliability using the Kappa coefficient (κ). The overall Kappa coefficient for all cases was 0.56, which represents moderate reliability. Kappa values describing interobserver agreement were 0.80 for type A injuries, 0.68 for type B injuries and 0.72 for type C injuries, all representing substantial reliability. The lowest level of agreement for specific subtypes was for fracture subtype A4 (Kappa = 0.19). Intraobserver analysis demonstrated overall average Kappa statistic for subtype grading of 0.68 also representing substantial reproducibility. In a worldwide sample of spinal surgeons without previous exposure to the recently described AOSpine Thoracolumbar Spine Injury Classification System, we demonstrated moderate interobserver and substantial intraobserver reliability. These results suggest that most spine surgeons can reliably apply this system to spine trauma patients as or more reliably than previously described systems.

A Brain-Machine-Muscle Interface for Restoring Hindlimb Locomotion after Complete Spinal Transection in Rats

PubMed Central

Alam, Monzurul; Chen, Xi; Zhang, Zicong; Li, Yan; He, Jufang

2014-01-01

A brain-machine interface (BMI) is a neuroprosthetic device that can restore motor function of individuals with paralysis. Although the feasibility of BMI control of upper-limb neuroprostheses has been demonstrated, a BMI for the restoration of lower-limb motor functions has not yet been developed. The objective of this study was to determine if gait-related information can be captured from neural activity recorded from the primary motor cortex of rats, and if this neural information can be used to stimulate paralysed hindlimb muscles after complete spinal cord transection. Neural activity was recorded from the hindlimb area of the primary motor cortex of six female Sprague Dawley rats during treadmill locomotion before and after mid-thoracic transection. Before spinal transection there was a strong association between neural activity and the step cycle. This association decreased after spinal transection. However, the locomotive state (standing vs. walking) could still be successfully decoded from neural recordings made after spinal transection. A novel BMI device was developed that processed this neural information in real-time and used it to control electrical stimulation of paralysed hindlimb muscles. This system was able to elicit hindlimb muscle contractions that mimicked forelimb stepping. We propose this lower-limb BMI as a future neuroprosthesis for human paraplegics. PMID:25084446

Gap Junctions Contribute to the Regulation of Walking-Like Activity in the Adult Mudpuppy (Necturus Maculatus).

PubMed

Lavrov, Igor; Fox, Lyle; Shen, Jun; Han, Yingchun; Cheng, Jianguo

2016-01-01

Although gap junctions are widely expressed in the developing central nervous system, the role of electrical coupling of neurons and glial cells via gap junctions in the spinal cord in adults is largely unknown. We investigated whether gap junctions are expressed in the mature spinal cord of the mudpuppy and tested the effects of applying gap junction blocker on the walking-like activity induced by NMDA or glutamate in an in vitro mudpuppy preparation. We found that glial and neural cells in the mudpuppy spinal cord expressed different types of connexins that include connexin 32 (Cx32), connexin 36 (Cx36), connexin 37 (Cx37), and connexin 43 (Cx43). Application of a battery of gap junction blockers from three different structural classes (carbenexolone, flufenamic acid, and long chain alcohols) substantially and consistently altered the locomotor-like activity in a dose-dependent manner. In contrast, these blockers did not significantly change the amplitude of the dorsal root reflex, indicating that gap junction blockers did not inhibit neuronal excitability nonselectively in the spinal cord. Taken together, these results suggest that gap junctions play a significant modulatory role in the spinal neural networks responsible for the generation of walking-like activity in the adult mudpuppy.

Intrinsic and Extrinsic Contributions to Seated Balance in the Sagittal and Coronal Planes: Implications for Trunk Control After Spinal Cord Injury.

PubMed

Audu, Musa L; Triolo, Ronald J

2015-08-01

The contributions of intrinsic (passive) and extrinsic (active) properties of the human trunk, in terms of the simultaneous actions about the hip and spinal joints, to the control of sagittal and coronal seated balance were examined. Able-bodied (ABD) and spinal-cord-injured (SCI) volunteers sat on a moving platform which underwent small amplitude perturbations in the anterior-posterior (AP) and medial-lateral (ML) directions while changes to trunk orientation were measured. A linear parametric model that related platform movement to trunk angle was fit to the experimental data by identifying model parameters in the time domain. The results showed that spinal cord injury leads to a systematic reduction in the extrinsic characteristics, while most of the intrinsic characteristics were rarely affected. In both SCI and ABD individuals, passive characteristics alone were not enough to maintain seated balance. Passive stiffness in the ML direction was almost 3 times that in the AP direction, making more extrinsic mechanisms necessary for balance in the latter direction. Proportional and derivative terms of the extrinsic model made the largest contribution to the overall output from the active system, implying that a simple proportional plus derivative (PD) controller structure will suffice for restoring seated balance after spinal cord injury.

Spatial Elucidation of Spinal Cord Lipid- and Metabolite- Regulations in Amyotrophic Lateral Sclerosis

NASA Astrophysics Data System (ADS)

Hanrieder, Jörg; Ewing, Andrew G.

2014-06-01

Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressing disease of the central nervous system that is characterized by motor neuron degeneration in the brain stem and the spinal cord. We employed time of flight secondary ion mass spectrometry (ToF-SIMS) to profile spatial lipid- and metabolite- regulations in post mortem human spinal cord tissue from ALS patients to investigate chemical markers of ALS pathogenesis. ToF-SIMS scans and multivariate analysis of image and spectral data were performed on thoracic human spinal cord sections. Multivariate statistics of the image data allowed delineation of anatomical regions of interest based on their chemical identity. Spectral data extracted from these regions were compared using two different approaches for multivariate statistics, for investigating ALS related lipid and metabolite changes. The results show a significant decrease for cholesterol, triglycerides, and vitamin E in the ventral horn of ALS samples, which is presumably a consequence of motor neuron degeneration. Conversely, the biogenic mediator lipid lysophosphatidylcholine and its fragments were increased in ALS ventral spinal cord, pointing towards neuroinflammatory mechanisms associated with neuronal cell death. ToF-SIMS imaging is a promising approach for chemical histology and pathology for investigating the subcellular mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis.

Differential expression of ryanodine receptor isoforms after spinal cord injury.

PubMed

Pelisch, Nicolas; Gomes, Cynthia; Nally, Jacqueline M; Petruska, Jeffrey C; Stirling, David P

2017-11-01

Ryanodine receptors (RyRs) are highly conductive intracellular Ca 2+ release channels and are widely expressed in many tissues, including the central nervous system. RyRs have been implicated in intracellular Ca 2+ overload which can drive secondary damage following traumatic injury to the spinal cord (SCI), but the spatiotemporal expression of the three isoforms of RyRs (RyR1-3) after SCI remains unknown. Here, we analyzed the gene and protein expression of RyR isoforms in the murine lumbar dorsal root ganglion (DRG) and the spinal cord lesion site at 1, 2 and 7 d after a mild contusion SCI. Quantitative RT PCR analysis revealed that RyR3 was significantly increased in lumbar DRGs and at the lesion site at 1 and 2 d post contusion compared to sham (laminectomy only) controls. Additionally, RyR2 expression was increased at 1 d post injury within the lesion site. RyR2 and -3 protein expression was localized to lumbar DRG neurons and their spinal projections within the lesion site acutely after SCI. In contrast, RyR1 expression within the DRG and lesion site remained unaltered following trauma. Our study shows that SCI initiates acute differential expression of RyR isoforms in DRG and spinal cord. Copyright © 2017 Elsevier B.V. All rights reserved.

Responses of dorsal spinal cord blood flow to noxious mechanical stimulation of the skin in anesthetized rats.

PubMed

Toda, Hiroko; Maruyama, Hitoshi; Budgell, Brian; Kurosawa, Mieko

2008-08-01

In urethane-anesthetized, artificially ventilated rats, alterations in dorsal spinal cord blood flow (SCBF) at the L4-6 level were measured with laser Doppler flowmetry in response to noxious mechanical cutaneous stimulation (pinching) of either a forepaw or a hindpaw. The stimulation was delivered ipsilaterally or contralaterally to the site of blood flow measurement. Pinching of the forepaw or the hindpaw on either side increased mean arterial pressure (MAP) to the same degree. However, the SCBF response to pinching of the ipsilateral hindpaw was significantly greater than that to other stimulations. These responses were not influenced by denervation of the baroreceptors. The responses of SCBF to pinching of the ipsilateral hindpaw persisted both after treatment with phenoxybenzamine and after spinalization at the C1-2 level, whereas the responses to pinching at other sites disappeared. The responses of MAP to stimulation at all four sites became negligible after treatment with phenoxybenzamine and after spinalization at the C1-2 level. These results indicate that noxious mechanical stimulation of the skin produces increases in SCBF via two mechanisms: one is via an elevation of systemic arterial pressure; the other is via a localized spinal mechanism evoked by ipsilateral, segmental inputs.

A brain-machine-muscle interface for restoring hindlimb locomotion after complete spinal transection in rats.

PubMed

Alam, Monzurul; Chen, Xi; Zhang, Zicong; Li, Yan; He, Jufang

2014-01-01

A brain-machine interface (BMI) is a neuroprosthetic device that can restore motor function of individuals with paralysis. Although the feasibility of BMI control of upper-limb neuroprostheses has been demonstrated, a BMI for the restoration of lower-limb motor functions has not yet been developed. The objective of this study was to determine if gait-related information can be captured from neural activity recorded from the primary motor cortex of rats, and if this neural information can be used to stimulate paralysed hindlimb muscles after complete spinal cord transection. Neural activity was recorded from the hindlimb area of the primary motor cortex of six female Sprague Dawley rats during treadmill locomotion before and after mid-thoracic transection. Before spinal transection there was a strong association between neural activity and the step cycle. This association decreased after spinal transection. However, the locomotive state (standing vs. walking) could still be successfully decoded from neural recordings made after spinal transection. A novel BMI device was developed that processed this neural information in real-time and used it to control electrical stimulation of paralysed hindlimb muscles. This system was able to elicit hindlimb muscle contractions that mimicked forelimb stepping. We propose this lower-limb BMI as a future neuroprosthesis for human paraplegics.

A neural circuitry that emphasizes spinal feedback generates diverse behaviours of human locomotion

PubMed Central

Song, Seungmoon; Geyer, Hartmut

2015-01-01

Neural networks along the spinal cord contribute substantially to generating locomotion behaviours in humans and other legged animals. However, the neural circuitry involved in this spinal control remains unclear. We here propose a specific circuitry that emphasizes feedback integration over central pattern generation. The circuitry is based on neurophysiologically plausible muscle-reflex pathways that are organized in 10 spinal modules realizing limb functions essential to legged systems in stance and swing. These modules are combined with a supraspinal control layer that adjusts the desired foot placements and selects the leg that is to transition into swing control during double support. Using physics-based simulation, we test the proposed circuitry in a neuromuscular human model that includes neural transmission delays, musculotendon dynamics and compliant foot–ground contacts. We find that the control network is sufficient to compose steady and transitional 3-D locomotion behaviours including walking and running, acceleration and deceleration, slope and stair negotiation, turning, and deliberate obstacle avoidance. The results suggest feedback integration to be functionally more important than central pattern generation in human locomotion across behaviours. In addition, the proposed control architecture may serve as a guide in the search for the neurophysiological origin and circuitry of spinal control in humans. PMID:25920414

Robust prediction of three-dimensional spinal curve from back surface for non-invasive follow-up of scoliosis

NASA Astrophysics Data System (ADS)

Bergeron, Charles; Labelle, Hubert; Ronsky, Janet; Zernicke, Ronald

2005-04-01

Spinal curvature progression in scoliosis patients is monitored from X-rays, and this serial exposure to harmful radiation increases the incidence of developing cancer. With the aim of reducing the invasiveness of follow-up, this study seeks to relate the three-dimensional external surface to the internal geometry, having assumed that that the physiological links between these are sufficiently regular across patients. A database was used of 194 quasi-simultaneous acquisitions of two X-rays and a 3D laser scan of the entire trunk. Data was processed to sets of datapoints representing the trunk surface and spinal curve. Functional data analyses were performed using generalized Fourier series using a Haar basis and functional minimum noise fractions. The resulting coefficients became inputs and outputs, respectively, to an array of support vector regression (SVR) machines. SVR parameters were set based on theoretical results, and cross-validation increased confidence in the system's performance. Predicted lateral and frontal views of the spinal curve from the back surface demonstrated average L2-errors of 6.13 and 4.38 millimetres, respectively, across the test set; these compared favourably with measurement error in data. This constitutes a first robust prediction of the 3D spinal curve from external data using learning techniques.

X-ray phase-contrast computed tomography visualizes the microstructure and degradation profile of implanted biodegradable scaffolds after spinal cord injury

PubMed Central

Takashima, Kenta; Hoshino, Masato; Uesugi, Kentaro; Yagi, Naoto; Matsuda, Shojiro; Nakahira, Atsushi; Osumi, Noriko; Kohzuki, Masahiro; Onodera, Hiroshi

2015-01-01

Tissue engineering strategies for spinal cord repair are a primary focus of translational medicine after spinal cord injury (SCI). Many tissue engineering strategies employ three-dimensional scaffolds, which are made of biodegradable materials and have microstructure incorporated with viable cells and bioactive molecules to promote new tissue generation and functional recovery after SCI. It is therefore important to develop an imaging system that visualizes both the microstructure of three-dimensional scaffolds and their degradation process after SCI. Here, X-ray phase-contrast computed tomography imaging based on the Talbot grating interferometer is described and it is shown how it can visualize the polyglycolic acid scaffold, including its microfibres, after implantation into the injured spinal cord. Furthermore, X-ray phase-contrast computed tomography images revealed that degradation occurred from the end to the centre of the braided scaffold in the 28 days after implantation into the injured spinal cord. The present report provides the first demonstration of an imaging technique that visualizes both the microstructure and degradation of biodegradable scaffolds in SCI research. X-ray phase-contrast imaging based on the Talbot grating interferometer is a versatile technique that can be used for a broad range of preclinical applications in tissue engineering strategies. PMID:25537600

A web-based neurological pain classifier tool utilizing Bayesian decision theory for pain classification in spinal cord injury patients

NASA Astrophysics Data System (ADS)

Verma, Sneha K.; Chun, Sophia; Liu, Brent J.

2014-03-01

Pain is a common complication after spinal cord injury with prevalence estimates ranging 77% to 81%, which highly affects a patient's lifestyle and well-being. In the current clinical setting paper-based forms are used to classify pain correctly, however, the accuracy of diagnoses and optimal management of pain largely depend on the expert reviewer, which in many cases is not possible because of very few experts in this field. The need for a clinical decision support system that can be used by expert and non-expert clinicians has been cited in literature, but such a system has not been developed. We have designed and developed a stand-alone tool for correctly classifying pain type in spinal cord injury (SCI) patients, using Bayesian decision theory. Various machine learning simulation methods are used to verify the algorithm using a pilot study data set, which consists of 48 patients data set. The data set consists of the paper-based forms, collected at Long Beach VA clinic with pain classification done by expert in the field. Using the WEKA as the machine learning tool we have tested on the 48 patient dataset that the hypothesis that attributes collected on the forms and the pain location marked by patients have very significant impact on the pain type classification. This tool will be integrated with an imaging informatics system to support a clinical study that will test the effectiveness of using Proton Beam radiotherapy for treating spinal cord injury (SCI) related neuropathic pain as an alternative to invasive surgical lesioning.

A novel device for studying weight supported, quadrupedal overground locomotion in spinal cord injured rats

PubMed Central

Hamlin, Marvin; Traughber, Terrance; Reinkensmeyer, David J.; de Leon, Ray D.

2015-01-01

Background Providing weight support facilitates locomotion in spinal cord injured animals. To control weight support, robotic systems have been developed for treadmill stepping and more recently for overground walking. New Method We developed a novel device, the body weight supported ambulatory rodent trainer (i.e. BART). It has a small pneumatic cylinder that moves along a linear track above the rat. When air is supplied to the cylinder, the rats are lifted as they perform overground walking. We tested the BART device in rats that received a moderate spinal cord contusion injury and in normal rats. Locomotor training with the BART device was not performed. Results All of the rats learned to walk in the BART device. In the contused rats, significantly greater paw dragging and dorsal stepping occurred in the hindlimbs compared to normal. Providing weight support significantly raised hip position and significantly reduced locomotor deficits. Hindlimb stepping was tightly coupled to forelimb stepping but only when the contused rats stepped without weight support. Three weeks after the contused rats received a complete spinal cord transection, significantly fewer hindlimb steps were performed. Comparison with Existing Methods Relative to rodent robotic systems, the BART device is a simpler system for studying overground locomotion. The BART device lacks sophisticated control and sensing capability, but it can be assembled relatively easily and cheaply. Conclusions These findings suggest that the BART device is a useful tool for assessing quadrupedal, overground locomotion which is a more natural form of locomotion relative to treadmill locomotion. PMID:25794460

Bilateral Activity-Dependent Interactions in the Developing Corticospinal System

PubMed Central

Friel, Kathleen M.; Martin, John H.

2009-01-01

Activity-dependent competition between the corticospinal (CS) systems in each hemisphere drives postnatal development of motor skills and stable CS tract connections with contralateral spinal motor circuits. Unilateral restriction of motor cortex (M1) activity during an early postnatal critical period impairs contralateral visually guided movements later in development and in maturity. Silenced M1 develops aberrant connections with the contralateral spinal cord whereas the initially active M1, in the other hemisphere, develops bilateral connections. In this study, we determined whether the aberrant pattern of CS tract terminations and motor impairments produced by early postnatal M1 activity restriction could be abrogated by reducing activity-dependent synaptic competition from the initially active M1 later in development. We first inactivated M1 unilaterally between postnatal weeks 5–7. We next inactivated M1 on the other side from weeks 7–11 (alternate inactivation), to reduce the competitive advantage that this side may have over the initially inactivated side. Alternate inactivation redirected aberrant contralateral CS tract terminations from the initially silenced M1 to their normal spinal territories and reduced the density of aberrant ipsilateral terminations from the initially active side. Normal movement endpoint control during visually guided locomotion was fully restored. This reorganization of CS terminals reveals an unsuspected late plasticity after the critical period for establishing the pattern of CS terminations in the spinal cord. Our findings show that robust bilateral interactions between the developing CS systems on each side are important for achieving balance between contralateral and ipsilateral CS tract connections and visuomotor control. PMID:17928450

Experience-dependent development of spinal motor neurons

NASA Technical Reports Server (NTRS)

Inglis, F. M.; Zuckerman, K. E.; Kalb, R. G.; Walton, K. D. (Principal Investigator)

2000-01-01

Locomotor activity in many species undergoes pronounced alterations in early postnatal life, and environmental cues may be responsible for modifying this process. To determine how these events are reflected in the nervous system, we studied rats reared under two different conditions-the presence or absence of gravity-in which the performance of motor operations differed. We found a significant effect of rearing environment on the size and complexity of dendritic architecture of spinal motor neurons, particularly those that are likely to participate in postural control. These results provide evidence that neurons subserving motor function undergo activity-dependent maturation in early postnatal life in a manner analogous to sensory systems.

Brain and spinal cord metabolic activity during propofol anaesthesia.

PubMed

Cavazzuti, M; Porro, C A; Barbieri, A; Galetti, A

1991-04-01

We have investigated the effects of propofol anaesthesia on the metabolic activity pattern of 35 regions of the rat brain and cervical spinal cord using the 14C-2-deoxyglucose technique. Anaesthesia was produced by an i.v. bolus of the commercial preparation of the drug (8 mg kg-1) and maintained with successive bolus administrations of 6 mg kg-1. Functional activity values (expressed as rates of local utilization of glucose) were reduced in 31 grey matter and two white matter structures in a propofol group relative both to saline-injected and vehicle-injected (aqueous emulsion containing 10% soya bean oil, 1.2% egg phosphatide and 2.25% glycerol) controls. Values from the two control groups did not differ significantly. Propofol-induced depression of metabolic activity was present in central nervous system regions belonging to sensory (auditory, visual and somatosensory), motor and limbic systems, including spinal cord grey matter. Mean percentage decreases ranged from 40% (vestibular nuclei) to 76% (cingulate cortex). Although these values may be slightly overestimated because of the modest increase in PaCo2 in the anaesthetized group, propofol appeared to elicit generalized reduction of central nervous system functional activity.

Calculation Of Correction Angles Of 3-Dimensional Vertebral Rotations Based On Bi-Plane X-Ray Photogrammetry

NASA Astrophysics Data System (ADS)

Tamaki, Tamotsu; Umezaki, Eisaku; Yamagata, Masatsune; Inoue, Shun-ichi

1984-10-01

For the therapy of diseases of spinal deformity such as scoliosis, the data of 3-dimensional and correct spinal configuration are needed. Authors developed the system of spinal configuration analysis using bi-plane X-ray photogrammetry which is strong aid for this subject. The idea of correction angle of rotation of vertebra is introduced for this system. Calculated result under this idea has the clinical meaning because the correction angle is the angle which should be corrected on the treatment such as operation or wearing the equipment. Method of 30° oblique projection which gives the apparent X-ray image and eases the measurement of the anatomically characteristic points is presented. The anatomically characteristic bony points whose images should be measured on a- or b-film are of four points. These are centers of upper and lower end plates of each vertebra the center is calculated from two points which are most distant each other on the contour of vertebral end plate ), the lower end points of root of right and left pedicles. Some clinical applications and the effectiveness of this system are presented.

Spinal α2-adrenergic and muscarinic receptors and the NO release cascade mediate supraspinally produced effectiveness of gabapentin at decreasing mechanical hypersensitivity in mice after partial nerve injury

PubMed Central

Takasu, Keiko; Honda, Motoko; Ono, Hideki; Tanabe, Mitsuo

2006-01-01

After partial nerve injury, the central analgesic effect of systemically administered gabapentin is mediated by both supraspinal and spinal actions. We further evaluate the mechanisms related to the supraspinally mediated analgesic actions of gabapentin involving the descending noradrenergic system. Intracerebroventricularly (i.c.v.) administered gabapentin (100 μg) decreased thermal and mechanical hypersensitivity in a murine chronic pain model that was prepared by partial ligation of the sciatic nerve. These effects were abolished by intrathecal (i.t.) injection of either yohimbine (3 μg) or idazoxan (3 μg), α2-adrenergic receptor antagonists. Pretreatment with atropine (0.3 mg kg−1, i.p. or 0.1 μg, i.t.), a muscarinic receptor antagonist, completely suppressed the effect of i.c.v.-injected gabapentin on mechanical hypersensitivity, whereas its effect on thermal hypersensitivity remained unchanged. Similar effects were obtained with pirenzepine (0.1 μg, i.t.), a selective M1-muscarinic receptor antagonist, but not with methoctramine (0.1 and 0.3 μg, i.t.), a selective M2-muscarinic receptor antagonist. The cholinesterase inhibitor neostigmine (0.3 ng, i.t.) potentiated only the analgesic effect of i.c.v. gabapentin on mechanical hypersensitivity, confirming spinal acetylcholine release downstream of the supraspinal action of gabapentin. Moreover, the effect of i.c.v. gabapentin on mechanical but not thermal hypersensitivity was reduced by i.t. injection of L-NAME (3 μg) or L-NMMA (10 μg), both of which are nitric oxide (NO) synthase inhibitors. Systemically administered naloxone (10 mg kg−1, i.p.), an opioid receptor antagonist, failed to suppress the analgesic actions of i.c.v. gabapentin, indicating that opioid receptors are not involved in activation of the descending noradrenergic system by gabapentin. Thus, the supraspinally mediated effect of gabapentin on mechanical hypersensitivity involves activation of spinal α2-adrenergic receptors followed by muscarinic receptors (most likely M1) and the NO cascade. In contrast, the effect of supraspinal gabapentin on thermal hypersensitivity is independent of the spinal cholinergic–NO system. PMID:16582934

Neurologic Diseases

MedlinePlus

... brain, spinal cord, and nerves make up the nervous system. Together they control all the workings of the ... something goes wrong with a part of your nervous system, you can have trouble moving, speaking, swallowing, breathing, ...

Regeneration of the Adult Rat Spinal Cord in Response to Ensheathing Cells and Methylprednisolone

DTIC Science & Technology

2002-01-01

me in academics and research, and also as my friend. I thank Dr. Linda L. Porter, for her continuous efforts on my behalf as the Chairperson of...and Spinal Cord Injury Program. We are grateful to Drs. Barbara S. Bregman and Linda L. Porter for their wonderful suggestions and guidance; to Anna...ES, Pietronigro DD, Seligman ML (1980) The free radical pathology and the microcirculation in the major central nervous system disorders. Acta

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

DTIC Science & Technology

2013-10-01

of this award, we have found that stretching negatively influences locomotor function in animals with both acute (within days) and chronic (after 3...stretching is stopped, and both acute and chronic animals show a similar time course of recovery. Finally, in very preliminary studies, we have found...glove, data acquisition system and software work very well. The results demonstrate that forces about the ankle of the rat during therapeutic

Fisetin exerts antihyperalgesic effect in a mouse model of neuropathic pain: engagement of spinal serotonergic system

PubMed Central

Zhao, Xin; Wang, Chuang; Cui, Wu-Geng; Ma, Qing; Zhou, Wen-Hua

2015-01-01

Fisetin, a natural flavonoid, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential antinociceptive efficacies of fisetin against neuropathic pain and explore mechanism(s). We subjected mice to chronic constriction injury (CCI) by loosely ligating the sciatic nerves, and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic fisetin treatment (5, 15 or 45 mg/kg, p.o.) ameliorated thermal hyperalgesia (but not mechanical allodynia) in CCI mice, concomitant with escalated levels of spinal monoamines and suppressed monoamine oxidase (MAO)-A activity. The antihyperalgesic action of fisetin was abolished by chemical depletion of spinal serotonin (5-HT) but potentiated by co-treatment with 5-HTP, a precursor of 5-HT. Moreover, intraperitoneal (i.p.) or intrathecal (i.t.) co-treatment with 5-HT7 receptor antagonist SB-258719 completely abrogated fisetin's antihyperalgesia. These findings confirm that chronic fisetin treatment exerts antinociceptive effect on thermal hyperalgesia in neuropathic mice, with spinal serotonergic system (coupled with 5-HT7) being critically involved. Of special benefit, fisetin attenuated co-morbidly behavioral symptoms of depression and anxiety (evaluated in forced swim test, novelty suppressed feeding test and light-dark test) evoked by neuropathic pain. PMID:25761874

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.

Uncoupling nicotine mediated motoneuron axonal pathfinding errors and muscle degeneration in zebrafish

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

Welsh, Lillian; Tanguay, Robert L.; Svoboda, Kurt R.

Zebrafish embryos offer a unique opportunity to investigate the mechanisms by which nicotine exposure impacts early vertebrate development. Embryos exposed to nicotine become functionally paralyzed by 42 hpf suggesting that the neuromuscular system is compromised in exposed embryos. We previously demonstrated that secondary spinal motoneurons in nicotine-exposed embryos were delayed in development and that their axons made pathfinding errors (Svoboda, K.R., Vijayaraghaven, S., Tanguay, R.L., 2002. Nicotinic receptors mediate changes in spinal motoneuron development and axonal pathfinding in embryonic zebrafish exposed to nicotine. J. Neurosci. 22, 10731-10741). In that study, we did not consider the potential role that altered skeletalmore » muscle development caused by nicotine exposure could play in contributing to the errors in spinal motoneuron axon pathfinding. In this study, we show that an alteration in skeletal muscle development occurs in tandem with alterations in spinal motoneuron development upon exposure to nicotine. The alteration in the muscle involves the binding of nicotine to the muscle-specific AChRs. The nicotine-induced alteration in muscle development does not occur in the zebrafish mutant (sofa potato, [sop]), which lacks muscle-specific AChRs. Even though muscle development is unaffected by nicotine exposure in sop mutants, motoneuron axonal pathfinding errors still occur in these mutants, indicating a direct effect of nicotine exposure on nervous system development.« less

Dual spinal lesion paradigm in the cat: evolution of the kinematic locomotor pattern.

PubMed

Barrière, Grégory; Frigon, Alain; Leblond, Hugues; Provencher, Janyne; Rossignol, Serge

2010-08-01

The recovery of voluntary quadrupedal locomotion after an incomplete spinal cord injury can involve different levels of the CNS, including the spinal locomotor circuitry. The latter conclusion was reached using a dual spinal lesion paradigm in which a low thoracic partial spinal lesion is followed, several weeks later, by a complete spinal transection (i.e., spinalization). In this dual spinal lesion paradigm, cats can express hindlimb walking 1 day after spinalization, a process that normally takes several weeks, suggesting that the locomotor circuitry within the lumbosacral spinal cord had been modified after the partial lesion. Here we detail the evolution of the kinematic locomotor pattern throughout the dual spinal lesion paradigm in five cats to gain further insight into putative neurophysiological mechanisms involved in locomotor recovery after a partial spinal lesion. All cats recovered voluntary quadrupedal locomotion with treadmill training (3-5 days/wk) over several weeks. After the partial lesion, the locomotor pattern was characterized by several left/right asymmetries in various kinematic parameters, such as homolateral and homologous interlimb coupling, cycle duration, and swing/stance durations. When no further locomotor improvement was observed, cats were spinalized. After spinalization, the hindlimb locomotor pattern rapidly reappeared, but left/right asymmetries in swing/stance durations observed after the partial lesion could disappear or reverse. It is concluded that, after a partial spinal lesion, the hindlimb locomotor pattern was actively maintained by new dynamic interactions between spinal and supraspinal levels but also by intrinsic changes within the spinal cord.

Subdural Thoracolumbar Spine Hematoma after Spinal Anesthesia: A Rare Occurrence and Literature Review of Spinal Hematomas after Spinal Anesthesia

PubMed Central

Maddali, Prasanthi; Walker, Blake; Fisahn, Christian; Page, Jeni; Diaz, Vicki; Zwillman, Michael E; Oskouian, Rod J; Tubbs, R. Shane

2017-01-01

Spinal hematomas are a rare but serious complication of spinal epidural anesthesia and are typically seen in the epidural space; however, they have been documented in the subdural space. Spinal subdural hematomas likely exist within a traumatically induced space within the dural border cell layer, rather than an anatomical subdural space. Spinal subdural hematomas present a dangerous clinical situation as they have the potential to cause significant compression of neural elements and can be easily mistaken for spinal epidural hematomas. Ultrasound can be an effective modality to diagnose subdural hematoma when no epidural blood is visualized. We have reviewed the literature and present a full literature review and a case presentation of an 82-year-old male who developed a thoracolumbar spinal subdural hematoma after spinal epidural anesthesia. Anticoagulant therapy is an important predisposing risk factor for spinal epidural hematomas and likely also predispose to spinal subdural hematomas. It is important to consider spinal subdural hematomas in addition to spinal epidural hematomas in patients who develop weakness after spinal epidural anesthesia, especially in patients who have received anticoagulation. PMID:28357164

Increased intracranial pressure

MedlinePlus

... the membranes covering the brain and spinal cord) Subdural hematoma (bleeding between the covering of the brain and ... intracranial pressure Patient Instructions Ventriculoperitoneal shunt - discharge Images Subdural hematoma Central nervous system and peripheral nervous system References ...

Needle puncture in rabbit functional spinal units alters rotational biomechanics.

PubMed

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

2015-04-01

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

Activity-dependent plasticity in spinal cord injury

PubMed Central

Lynskey, James V.; Belanger, Adam; Jung, Ranu

2008-01-01

The adult mammalian central nervous system (CNS) is capable of considerable plasticity, both in health and disease. After spinal neurotrauma, the degrees and extent of neuroplasticity and recovery depend on multiple factors, including the level and extent of injury, postinjury medical and surgical care, and rehabilitative interventions. Rehabilitation strategies focus less on repairing lost connections and more on influencing CNS plasticity for regaining function. Current evidence indicates that strategies for rehabilitation, including passive exercise, active exercise with some voluntary control, and use of neuroprostheses, can enhance sensorimotor recovery after spinal cord injury (SCI) by promoting adaptive structural and functional plasticity while mitigating maladaptive changes at multiple levels of the neuraxis. In this review, we will discuss CNS plasticity that occurs both spontaneously after SCI and in response to rehabilitative therapies. PMID:18566941

Quadriplegia after parathyroidectomy in a hemodialysis patient.

PubMed

Wang, Yu-Chieh; Huang, Shih-Yu; Lin, Ho-Tien; Hu, Jenkin-S; Chan, Kwok-Hon; Tsou, Mei-Yung

2011-03-01

We present a case of post-operative iatrogenic quadriplegia, which occurred after subtotal parathyroidectomy. This patient was on long-term hemodialysis for 7 years. The need of prolonged neck extension for this procedure was probably the main risk factor for the spinal cord injury. Systemic hypotension which contributed to the injury in this case, should be anticipated and promptly treated to prevent further damage. Spinal deformities associated with end-stage renal disease may make such patients more susceptible. Since appropriate precautions against potential neurologic damage can be undertaken, we suggest that evaluating carefully for the pre-existing spinal stenosis before a procedure requiring prominent and prolonged hyper-extension of the neck, especially in long-term hemodialysis patients is of paramount importance. Copyright © 2011. Published by Elsevier B.V.

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

AxiaLIF system: minimally invasive device for presacral lumbar interbody spinal fusion

PubMed Central

Rapp, Steven M; Miller, Larry E; Block, Jon E

2011-01-01

Lumbar fusion is commonly performed to alleviate chronic low back and leg pain secondary to disc degeneration, spondylolisthesis with or without concomitant lumbar spinal stenosis, or chronic lumbar instability. However, the risk of iatrogenic injury during traditional anterior, posterior, and transforaminal open fusion surgery is significant. The axial lumbar interbody fusion (AxiaLIF) system is a minimally invasive fusion device that accesses the lumbar (L4–S1) intervertebral disc spaces via a reproducible presacral approach that avoids critical neurovascular and musculoligamentous structures. Since the AxiaLIF system received marketing clearance from the US Food and Drug Administration in 2004, clinical studies of this device have reported high fusion rates without implant subsidence, significant improvements in pain and function, and low complication rates. This paper describes the design and approach of this lumbar fusion system, details the indications for use, and summarizes the clinical experience with the AxiaLIF system to date. PMID:22915939

AxiaLIF system: minimally invasive device for presacral lumbar interbody spinal fusion.

PubMed

Rapp, Steven M; Miller, Larry E; Block, Jon E

2011-01-01

Lumbar fusion is commonly performed to alleviate chronic low back and leg pain secondary to disc degeneration, spondylolisthesis with or without concomitant lumbar spinal stenosis, or chronic lumbar instability. However, the risk of iatrogenic injury during traditional anterior, posterior, and transforaminal open fusion surgery is significant. The axial lumbar interbody fusion (AxiaLIF) system is a minimally invasive fusion device that accesses the lumbar (L4-S1) intervertebral disc spaces via a reproducible presacral approach that avoids critical neurovascular and musculoligamentous structures. Since the AxiaLIF system received marketing clearance from the US Food and Drug Administration in 2004, clinical studies of this device have reported high fusion rates without implant subsidence, significant improvements in pain and function, and low complication rates. This paper describes the design and approach of this lumbar fusion system, details the indications for use, and summarizes the clinical experience with the AxiaLIF system to date.

Involvement of the avian song system in reproductive behaviour

PubMed Central

Wild, J. Martin; Botelho, João F.

2015-01-01

The song system of songbirds consists of an interconnected set of forebrain nuclei that has traditionally been regarded as dedicated to the learning and production of song. Here, however, we suggest that the song system could also influence muscles used in reproductive behaviour, such as the cloacal sphincter muscle. We show that the same medullary nucleus, retroambigualis (RAm), that projects upon spinal motoneurons innervating expiratory muscles (which provide the pressure head for vocalization) and upon vocal motoneurons for respiratory–vocal coordination also projects upon cloacal motoneurons. Furthermore, RAm neurons projecting to sacral spinal levels were shown to receive direct projections from nucleus robustus arcopallialis (RA) of the forebrain song system. Thus, by indicating a possible disynaptic relationship between RA and motoneurons innervating the reproductive organ, in both males and females, these results potentially extend the role of the song system to include consummatory as well as appetitive aspects of reproductive behaviour. PMID:26631245

Active uptake of substance P carboxy-terminal heptapeptide (5-11) into rat brain and rabbit spinal cord slices.

PubMed

Nakata, Y; Kusaka, Y; Yajima, H; Segawa, T

1981-12-01

We previously reported that nerve terminals and glial cells lack an active uptake system capable of terminating transmitter action of substance P (SP). In the present study, we demonstrated the existence of an active uptake system for SP carboxy-terminal heptapeptide, (5-11)SP. When the slices from either rat brain or rabbit spinal cord were incubated with [3H](5-11)SP, the uptake of (5-11)SP into slices was observed. The uptake system has the properties of an active transport mechanism: it is dependent on temperature and sensitive to hypoosmotic treatment and is inhibited by ouabain and dinitrophenol (DNP). In the brain, (5-11)SP was accumulated by means of a high-affinity and a low-affinity uptake system. The Km and the Vmax values for the high-affinity system were 4.20 x 10(-8) M and 7.59 fmol/10 mg wet weight/min, respectively, whereas these values for the low-affinity system were 1.00 x 10(-6) M and 100 fmol/10 mg wet weight/min, respectively. In the spinal cord, there was only one uptake system, with a Km value of 2.16 x 10(-7) M and Vmax value of 26.2 fmol/10 mg wet weight/min. These results suggest that when SP is released from nerve terminals, it is hydrolysed into (5-11)SP before or after acting as a neurotransmitter, which is in turn accumulated into nerve terminals. Therefore, the uptake system may represent a possible mechanism for the inactivation of SP.

Adult-onset intradural spinal teratoma: report of 18 consecutive cases and outcomes in a single center.

PubMed

Wan, Wei; Yang, Cheng; Yan, Wangjun; Liu, Tielong; Yang, Xinghai; Song, Dianwen; Xiao, Jianru

2017-07-01

Eighteen consecutive patients with adult-onset intradural spinal teratoma underwent surgical treatment in our center from 1998 to 2013. Teratoma is defined as a neoplasm composed of elements derived from three germ cell layers (ectoderm, endoderm and mesoderm). Intraspinal teratoma is extremely rare and accounts for 0.2-0.5% of all spinal cord tumors. Moreover, teratoma occurs primarily in neonates and young children. Adult-onset intradural spinal teratoma is even rare. The aim of this study was to discuss the clinical characteristics, diagnosis and therapeutic strategies of adult-onset intradural spinal teratoma. This retrospective study included 18 consecutive adult patients with intradural teratoma who were surgically treated in our center between 1998 and 2013. The clinical features, pathogenesis, diagnostic strategies and surgical outcomes were discussed. Neurological function outcomes were evaluated by the JOA scoring system. Of the 18 included patients, 4 patients received subtotal resection and the other 14 patients received total resection. All the 18 cases were diagnosed with mature teratoma. The mean follow-up period was 79.7 (median 60.5; range 27-208) months. Local recurrence occurred in two of the four patients who underwent subtotal resection and in no patient who underwent total resection. The neurologic status improved in 16 cases and remained unchanged in the other two patients. Adult-onset intradural spinal teratoma is extremely rare. To the best of our knowledge, this is the largest series of patients with this disease. Despite the slow-growth and indolent nature, radical resection remains the recommended treatment to reduce tumor recurrence.

Distinct roles of oxidative stress and antioxidants in the nucleus dorsalis and red nucleus following spinal cord hemisection.

PubMed

Xu, Mei; Yip, George Wai-Cheong; Gan, Le-Ting; Ng, Yee-Kong

2005-09-07

Oxidative stress plays an important role in the pathogenesis of neurodegeneration after the acute central nervous system injury. We reported previously that increased nitric oxide (NO) production following spinal cord hemisection tends to lead to neurodegeneration in neurons of the nucleus dorsalis (ND) that normally lacks expression of neuronal NO synthase (nNOS) in opposition to those in the red nucleus (RN) that constitutively expresses nNOS. We wondered whether oxidative stress could be a mechanism underlying this NO involved neurodegeneration. In the present study, we examined oxidative damage evaluated by the presence of 4-hydroxynonenal (HNE) and iron accumulation and expression of putative antioxidant enzymes heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) in neurons of the ND and RN after spinal cord hemisection. We found that HNE expression was induced in neurons of the ipsilateral ND from 1 to 14 days following spinal cord hemisection. Concomitantly, iron staining was seen from 7 to 14 days after lesion. HO-1, however, was only transiently induced in ipsilateral ND neurons between 3 and 7 days after lesion. In contrast to the ND neurons, HNE was undetectable and iron level was unaltered in the RN neurons after spinal cord hemisection. HO-1, SOD-Cu/Zn and SOD-Mn were constitutively expressed in RN neurons, and lesion to the spinal cord did not change their expression. These results suggest that oxidative stress is involved in the degeneration of the lesioned ND neurons; whereas constitutive antioxidant enzymes may protect the RN neurons from oxidative damage.

On-scene treatment of spinal injuries in motor sports.

PubMed

Kreinest, M; Scholz, M; Trafford, P

2017-04-01

Because spinal cord injuries can have fatal consequences for injured race car drivers, prehospital treatment of spinal injuries is a major concern in motor sports. A structured procedure for assessing trauma patients and their treatment should follow established ABCDE principles. Only then, a stable patient could be further examined and appropriate measures can be undertaken. For patients in an acute life-threatening condition, rapid transport must be initiated and should not be delayed by measures that are not indicated. If a competitor must first be extricated from the racing vehicle, the correct method of extrication must be chosen. To avoid secondary injury to the spine after a racing accident, in-line extrication from the vehicle and immobilization of the patient are standard procedures in motor sports and have been used for decades. Since immobilization can be associated with disadvantages and complications, the need for immobilization of trauma patients outside of motor sports medicine has become the subject of an increasing number of reports in the scientific literature. Even in motor sports, where specific safety systems that offer spinal protection are present, the indications for spinal immobilization need to be carefully considered rather than being blindly adopted as a matter of course. The aim of this article is to use recent literature to present an overview about the treatment of spinal injuries in motor sports. Further, we present a new protocol for indications for immobilizing the spine in motor sports that is based on the ABCDE principles and takes into account the condition of the patient.

Comparison of hydrocephalus appearance at spinaldysraphia.

PubMed

Elshani, Besnik; Lenjani, Basri

2013-01-01

Congenital malformation of spinal dysraphism followed by hydrocephalus are phenomenon reveals during intrauterine child growth. Prime objective of this work was to present Comparison of hydrocephalus appearance at spinal dysraphism respectively at its meningocele and myelomeningocele forms in Neurosurgery Clinic in UCC in Prishtina. It is perfected with retrospective and prospective method precisely of its epidemiologic part summarizing notices from patients' histories which in 2000-2006 are hospitalized in Neurosurgery Clinic from (QFLPK)--Pediatric Clinic and Children Box (Department)--Gynecology Clinic and from Sanitary Regional Center throughout Kosova. Our study objects were two groups, as the first group 90 patients with spinal dysraphism where neurosurgery operations were done and classified types of dysraphism. At myelomeningocele hydrocephalus has dominated and in a percent of appearance and as acute of its active form was 97% of hydrocephalus form where subjected to cerebrospinal liquid derivation with ventriculo -peritoneal shunt in comparison with meningocele we do not have involvation of spinal nerve element, hydrocephalus takes active form with intervention indication in 60% of cases. Reflection in shown deficit aspect is totally different at myelomeningoceles where lower paraplegia dominate more than paraparesis. The second patient operative technique developed by hydrocephalus with neurosurgical intervention indication has to do with placing of (VP) ventriculo- peritoneal system (shant) at myelomeningoceles with hydrocephalus 58 cases and 12 cases meningoceles with hydrocephalus. Post operative meningitis (shant meningitis): from 70 operated cases of hydrocephalus with spinal dysraphism shunts complications from all types are just cases. Finally that appearance of hydrocephalus compared at spinal dysraphism dominate at myellomeningoceles as in notice time aspect, it is persisting and further acute, with vital motivation for neurosurgical intervention.

Acute Communicating Hydrocephalus as Spinal Cord Surgery Complication in Patient with Lumbar Lipomyelocele.

PubMed

Prior, Alessandro; Severino, Mariasavina; Rossi, Andrea; Pavanello, Marco; Piatelli, Gianluca; Consales, Alessandro

2018-04-17

A lumbar lipomyelocele is a closed spinal dysraphism that can cause tethered cord syndrome. Between 5% and 15% of spinal dysraphism surgery cases are burdened with complications, the most common being wound infections or dehiscence and cerebrospinal fluid leak. Acute communicating hydrocephalus has never been described as a complication of this type of surgery. A 6-year-old girl who had undergone several surgeries in another institution for lumbar lipomyeloschisis came to our attention for a second opinion about the management of her spinal dysraphism. During the visit, she experienced sudden loss of consciousness. An emergent computed tomography scan revealed an acute communicating hydrocephalus. External ventricular drainage was performed with quick recovery of consciousness. Further craniospinal magnetic resonance imaging revealed small droplets of fat in the intracranial subarachnoid spaces and ventricular system, suggestive of rupture of the lipoma with consequent aseptic meningitis. This is the first description of acute communicating hydrocephalus as a complication of lipomyelocele surgery. We discuss the possible pathophysiologic mechanisms leading to cerebrospinal fluid dynamics alteration. Copyright © 2018 Elsevier Inc. All rights reserved.

Management of acute traumatic spinal cord injuries.

PubMed

Shank, C D; Walters, B C; Hadley, M N

2017-01-01

Acute traumatic spinal cord injury (SCI) is a devastating disease process affecting tens of thousands of people across the USA each year. Despite the increase in primary prevention measures, such as educational programs, motor vehicle speed limits, automobile running lights, and safety technology that includes automobile passive restraint systems and airbags, SCIs continue to carry substantial permanent morbidity and mortality. Medical measures implemented following the initial injury are designed to limit secondary insult to the spinal cord and to stabilize the spinal column in an attempt to decrease devastating sequelae. This chapter is an overview of the contemporary management of an acute traumatic SCI patient from the time of injury through the stay in the intensive care unit. We discuss initial triage, immobilization, and transportation of the patient by emergency medical services personnel to a definitive treatment facility. Upon arrival at the emergency department, we review initial trauma protocols and the evidence-based recommendations for radiographic evaluation of the patient's vertebral column. Finally, we outline closed cervical spine reduction and various aggressive medical therapies aimed at improving neurologic outcome. © 2017 Elsevier B.V. All rights reserved.

Gene Delivery Strategies to Promote Spinal Cord Repair

PubMed Central

Walthers, Christopher M; Seidlits, Stephanie K

2015-01-01

Gene therapies hold great promise for the treatment of many neurodegenerative disorders and traumatic injuries in the central nervous system. However, development of effective methods to deliver such therapies in a controlled manner to the spinal cord is a necessity for their translation to the clinic. Although essential progress has been made to improve efficiency of transgene delivery and reduce the immunogenicity of genetic vectors, there is still much work to be done to achieve clinical strategies capable of reversing neurodegeneration and mediating tissue regeneration. In particular, strategies to achieve localized, robust expression of therapeutic transgenes by target cell types, at controlled levels over defined time periods, will be necessary to fully regenerate functional spinal cord tissues. This review summarizes the progress over the last decade toward the development of effective gene therapies in the spinal cord, including identification of appropriate target genes, improvements to design of genetic vectors, advances in delivery methods, and strategies for delivery of multiple transgenes with synergistic actions. The potential of biomaterials to mediate gene delivery while simultaneously providing inductive scaffolding to facilitate tissue regeneration is also discussed. PMID:25922572

EphrinB3/EphA4-mediated guidance of ascending and descending spinal tracts.

PubMed

Paixão, Sónia; Balijepalli, Aarathi; Serradj, Najet; Niu, Jingwen; Luo, Wenqin; Martin, John H; Klein, Rüdiger

2013-12-18

The spinal cord contains many descending and ascending longitudinal tracts whose development appears to be controlled by distinct guidance systems. We identified a population of dorsal spinal neurons marked by coexpression of the transcription factor Zic2 and the guidance receptor EphA4. Zic2+;EphA4+ neurons are surrounded by mechanosensory terminals, suggesting innervation by mechanoreceptor afferents. Their axons form an ipsilateral ascending pathway that develops during embryogenesis and projects within the ventral aspect of the dorsal funiculus, the same location as the descending corticospinal tract (CST), which develops postnatally. Interestingly, the same guidance mechanism, namely, ephrinB3-induced EphA4 forward signaling, is required for the guidance of both ascending and descending axon tracts. Our analysis of conditional EphA4 mutant mice also revealed that the development of the dorsal funiculus occurs independently of EphA4 expression in descending CST axons and is linked to the distribution of Zic2+;EphA4+ spinal neurons and the formation of the ascending pathway. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of Intrathecal Opioids Use in Cesarean Section on Breastfeeding and Newborns’ Weight Gaining

PubMed Central

Yousefshahi, Fardin; Davari-Tanha, Fatemeh; Najafi, Atabak; Kaveh, Mahbod; Rezaei Hemami, Mohsen; Khashayar, Patricia; Anbarafshan, Mohammad

2016-01-01

Objective: To assess the association between intrapartum intrathecal opioid use and breastfeeding and weight gain following cesarean section. Materials and methods: The prospective double-blinded study was conducted on term pregnant women, undergoing elective cesarean section under spinal anesthesia. They divided into two groups. In the first group, intrathecal Morphine was used to achieve analgesia during or after the operation. The remainder divided into two subgroups, those who did not receive any opioid or those received systemic opioids. Following labor breastfeeding accessed in a follow-up, two month latter. Results: There was no difference between the demographic variables of the mothers and newborns APGAR score and weight at the time of birth. Breastfeeding rate was similar in intrathecal group in compare with other patents (P value = 0.518). While, the infants’ weight at the end of second month was lower in spinal opioid group (P value = 0.036). Conclusion: The present study was the first to suggest that spinal (intrathecal) opioids do not have any impact on breastfeeding. However the relationship between spinal anesthesia on weight gaining needs more investigation. PMID:28546816

Effects of Intrathecal Opioids Use in Cesarean Section on Breastfeeding and Newborns' Weight Gaining.

PubMed

Yousefshahi, Fardin; Davari-Tanha, Fatemeh; Najafi, Atabak; Kaveh, Mahbod; Rezaei Hemami, Mohsen; Khashayar, Patricia; Anbarafshan, Mohammad

2016-12-01

Objective: To assess the association between intrapartum intrathecal opioid use and breastfeeding and weight gain following cesarean section. Materials and methods: The prospective double-blinded study was conducted on term pregnant women, undergoing elective cesarean section under spinal anesthesia. They divided into two groups. In the first group, intrathecal Morphine was used to achieve analgesia during or after the operation. The remainder divided into two subgroups, those who did not receive any opioid or those received systemic opioids. Following labor breastfeeding accessed in a follow-up, two month latter. Results: There was no difference between the demographic variables of the mothers and newborns APGAR score and weight at the time of birth. Breastfeeding rate was similar in intrathecal group in compare with other patents (P value = 0.518). While, the infants' weight at the end of second month was lower in spinal opioid group (P value = 0.036). Conclusion: The present study was the first to suggest that spinal (intrathecal) opioids do not have any impact on breastfeeding. However the relationship between spinal anesthesia on weight gaining needs more investigation.

The Role of Incentives in Changing the Behavior of Spinal Care Providers: A Primer on Behavioral Economics in Health Care.

PubMed

Sharan, Alok D; Schroeder, Gregory D; West, Michael E; Vaccaro, Alexander R

2016-12-01

As spinal care transitions from individual practitioners working in a volume-based reimbursement system toward multidisciplinary health care organizations working in a population-based model with value-based reimbursement, it is critical that insurance companies, administrators, and spine care provider have a clear understanding of how incentives change physician behavior. This article will introduce the concept of behavior economics, and discuss 9 principles relevant to physician decision-making.

Targeting central plasticity: a new direction of finding painkillers.

PubMed

Zhuo, Min

2005-01-01

It is well documented that sensory transmission, including pain, receives endogenous inhibitory modulatory influences at dorsal horn of the spinal cord. Recent results, from behavioral to molecular studies, demonstrate that injury caused plastic changes in forebrain areas. In addition to encoding pain, these supraspinal areas may also affect pain transmission in the spinal cord level by activating "top-down" descending facilitatory systems. In this review, I provide review of evidence related to these new progresses, from human brain imaging to work from genetically mutant mice.

A comparison of 25 gauge Quincke spinal needle with 26 gauge Eldor spinal needle for the elective Caesarian sections: insertion characteristics and complications.

PubMed

Tabedar, S; Maharjan, S K; Shrestha, B R; Shrestha, B M

2003-01-01

The study was designed to compare the insertion characteristics and incidence of PDPH between 25 gauge Quincke needle and 26 gauge Eldor needle for spinal anaesthesia in elective c/s. 60 pregnant women (aged 19-35 yrs and weighing 58 -67 kg) undergoing elective caesarean section were randomized into group A (Quincke spinal needle group) or group B (Eldor spinal needle group). Spinal anaesthesia was performed with 2.9 ml 0.5% heavy bupivacaine using 25 gauge Quincke spinal needle in group A and 26 Gauge Eldor spinal needle in group B. Onset, time of first identification of backflow of CSF, number of attempts, level of sensory and motor blockade, failure of anaesthesia, inadequate anaesthesia and incidence of PDPH were recorded. Quincke spinal needle was found easy at insertion, first attempt was successful in 90% of cases, whereas Eldor spinal needle was successful at first attempt in only 60% of cases. Early identification of CSF was seen in Eldor spinal needle group in 3.5 seconds vs. 5.2 seconds in Quincke spinal needle group. Blood mixed CSF was seen in 8 Quincke spinal needle group vs. none in Eldor spinal needle group. Onset was similar between both groups i.e. in 6 minutes. Failure of anaesthesia was none in Eldor spinal needle group vs. 2 in quincke spinal needle group. Height of sensory block achieved was T4 level in 26 parturients,T6 in 1 ,T8 in 1 and no anaesthesia at all in another 2 parturient as compared to T4 level in 29 and T3 in 1 parturient in Eldor spinal needle group. The degree of motor block with the use of Bromage criteria showed a motor score of 1 or 2 in 26 parturients in Quincke spinal needle group vs. same in all cases in Eldor spinal needle group. The total incidence of PDPH was 8.3 % (5 out of 60 parturient) which occurred all in Quincke spinal needle group. 2 parturient who developed severe PDPH required epidural blood patch. 26 gauge Eldor spinal needle was found to be better than 25 gauge Quincke spinal needle for caesarian sections to decrease the incidence of PDPH, though not all insertion characteristics were in favour of the Eldor needle.

Combined motor cortex and spinal cord neuromodulation promotes corticospinal system functional and structural plasticity and motor function after injury.

PubMed

Song, Weiguo; Amer, Alzahraa; Ryan, Daniel; Martin, John H

2016-03-01

An important strategy for promoting voluntary movements after motor system injury is to harness activity-dependent corticospinal tract (CST) plasticity. We combine forelimb motor cortex (M1) activation with co-activation of its cervical spinal targets in rats to promote CST sprouting and skilled limb movement after pyramidal tract lesion (PTX). We used a two-step experimental design in which we first established the optimal combined stimulation protocol in intact rats and then used the optimal protocol in injured animals to promote CST repair and motor recovery. M1 was activated epidurally using an electrical analog of intermittent theta burst stimulation (iTBS). The cervical spinal cord was co-activated by trans-spinal direct current stimulation (tsDCS) that was targeted to the cervical enlargement, simulated from finite element method. In intact rats, forelimb motor evoked potentials (MEPs) were strongly facilitated during iTBS and for 10 min after cessation of stimulation. Cathodal, not anodal, tsDCS alone facilitated MEPs and also produced a facilitatory aftereffect that peaked at 10 min. Combined iTBS and cathodal tsDCS (c-tsDCS) produced further MEP enhancement during stimulation, but without further aftereffect enhancement. Correlations between forelimb M1 local field potentials and forelimb electromyogram (EMG) during locomotion increased after electrical iTBS alone and further increased with combined stimulation (iTBS+c-tsDCS). This optimized combined stimulation was then used to promote function after PTX because it enhanced functional connections between M1 and spinal circuits and greater M1 engagement in muscle contraction than either stimulation alone. Daily application of combined M1 iTBS on the intact side and c-tsDCS after PTX (10 days, 27 min/day) significantly restored skilled movements during horizontal ladder walking. Stimulation produced a 5.4-fold increase in spared ipsilateral CST terminations. Combined neuromodulation achieves optimal motor recovery and substantial CST outgrowth with only 27 min of daily stimulation compared with 6h, as in our prior study, making it a potential therapy for humans with spinal cord injury. Copyright © 2015 Elsevier Inc. All rights reserved.

Spine detection in CT and MR using iterated marginal space learning.

PubMed

Michael Kelm, B; Wels, Michael; Kevin Zhou, S; Seifert, Sascha; Suehling, Michael; Zheng, Yefeng; Comaniciu, Dorin

2013-12-01

Examinations of the spinal column with both, Magnetic Resonance (MR) imaging and Computed Tomography (CT), often require a precise three-dimensional positioning, angulation and labeling of the spinal disks and the vertebrae. A fully automatic and robust approach is a prerequisite for an automated scan alignment as well as for the segmentation and analysis of spinal disks and vertebral bodies in Computer Aided Diagnosis (CAD) applications. In this article, we present a novel method that combines Marginal Space Learning (MSL), a recently introduced concept for efficient discriminative object detection, with a generative anatomical network that incorporates relative pose information for the detection of multiple objects. It is used to simultaneously detect and label the spinal disks. While a novel iterative version of MSL is used to quickly generate candidate detections comprising position, orientation, and scale of the disks with high sensitivity, the anatomical network selects the most likely candidates using a learned prior on the individual nine dimensional transformation spaces. Finally, we propose an optional case-adaptive segmentation approach that allows to segment the spinal disks and vertebrae in MR and CT respectively. Since the proposed approaches are learning-based, they can be trained for MR or CT alike. Experimental results based on 42 MR and 30 CT volumes show that our system not only achieves superior accuracy but also is among the fastest systems of its kind in the literature. On the MR data set the spinal disks of a whole spine are detected in 11.5s on average with 98.6% sensitivity and 0.073 false positive detections per volume. On the CT data a comparable sensitivity of 98.0% with 0.267 false positives is achieved. Detected disks are localized with an average position error of 2.4 mm/3.2 mm and angular error of 3.9°/4.5° in MR/CT, which is close to the employed hypothesis resolution of 2.1 mm and 3.3°. Copyright © 2012 Elsevier B.V. All rights reserved.

Combined motor cortex and spinal cord neuromodulation promotes corticospinal system functional and structural plasticity and motor function after injury

PubMed Central

Song, Weiguo; Amer, Alzahraa; Ryan, Daniel; Martin, John H.

2016-01-01

An important strategy for promoting voluntary movements after motor system injury is to harness activity-dependent corticospinal tract (CST) plasticity. We combine forelimb motor cortex (M1) activation with co-activation of its cervical spinal targets in rats to promote CST sprouting and skilled limb movement after pyramidal tract lesion (PTX). We used a two-step experimental design in which we first established the optimal combined stimulation protocol in intact rats and then used the optimal protocol in injured animals to promote CST repair and motor recovery. M1 was activated epidurally using an electrical analog of intermittent theta burst stimulation (iTBS). The cervical spinal cord was co-activated by trans-spinal direct current stimulation (tsDCS) that was targeted to the cervical enlargement, simulated from finite element method. In intact rats, forelimb motor evoked potentials (MEPs) were strongly facilitated during iTBS and for 10 minutes after cessation of stimulation. Cathodal, not anodal, tsDCS alone facilitated MEPs and also produced a facilitatory aftereffect that peaked at 10 minutes. Combined iTBS and cathodal tsDCS (c-tsDCS) produced further MEP enhancement during stimulation, but without further aftereffect enhancement. Correlations between forelimb M1 local field potentials and forelimb electromyogram (EMG) during locomotion increased after electrical iTBS alone and further increased with combined stimulation (iTBS + c-tsDCS). This optimized combined stimulation was then used to promote function after PTX because it enhanced functional connections between M1 and spinal circuits and greater M1 engagement in muscle contraction than either stimulation alone. Daily application of combined M1 iTBS on the intact side and c-tsDCS after PTX (10 days, 27 minutes/day) significantly restored skilled movements during horizontal ladder walking. Stimulation produced a 5.4-fold increase in spared ipsilateral CST terminations. Combined neuromodulation achieves optimal motor recovery and substantial CST outgrowth with only 27 minutes of daily stimulation compared with 6 hours, as in our prior study, making it a potential therapy for humans with spinal cord injury. PMID:26708732

The dosimetric impact of implants on the spinal cord dose during stereotactic body radiotherapy.

PubMed

Yazici, Gozde; Sari, Sezin Yuce; Yedekci, Fazli Yagiz; Yucekul, Altug; Birgi, Sumerya Duru; Demirkiran, Gokhan; Gultekin, Melis; Hurmuz, Pervin; Yazici, Muharrem; Ozyigit, Gokhan; Cengiz, Mustafa

2016-05-25

The effects of spinal implants on dose distribution have been studied for conformal treatment plans. However, the dosimetric impact of spinal implants in stereotactic body radiotherapy (SBRT) treatments has not been studied in spatial orientation. In this study we evaluated the effect of spinal implants placed in sawbone vertebra models implanted as in vivo instrumentations. Four different spinal implant reconstruction techniques were performed using the standard sawbone lumbar vertebrae model; 1. L2-L4 posterior instrumentation without anterior column reconstruction (PI); 2. L2-L4 anterior instrumentation, L3 corpectomy, and anterior column reconstruction with a titanium cage (AIAC); 3. L2-L4 posterior instrumentation, L3 corpectomy, and anterior column reconstruction with a titanium cage (PIAC); 4. L2-L4 anterior instrumentation, L3 corpectomy, and anterior column reconstruction with chest tubes filled with bone cement (AIABc). The target was defined as the spinous process and lamina of the lumbar (L) 3 vertebra. A thermoluminescent dosimeter (TLD, LiF:Mg,Ti) was located on the measurement point anterior to the spinal cord. The prescription dose was 8 Gy and the treatment was administered in a single fraction using a CyberKnife® (Accuray Inc., Sunnyvale, CA, USA). We performed two different treatment plans. In Plan A beam interaction with the rod was not limited. In plan B the rod was considered a structure of avoidance, and interaction between the rod and beam was prevented. TLD measurements were compared with the point dose calculated by the treatment planning system (TPS). In plan A, the difference between TLD measurement and the dose calculated by the TPS was 1.7 %, 2.8 %, and 2.7 % for the sawbone with no implant, PI, and PIAC models, respectively. For the AIAC model the TLD dose was 13.8 % higher than the TPS dose; the difference was 18.6 % for the AIABc model. In plan B for the AIAC and AIABc models, TLD measurement was 2.5 % and 0.9 % higher than the dose calculated by the TPS, respectively. Spinal implants may be present in the treatment field in patients scheduled to undergo SBRT. For the types of implants studied herein anterior rod instrumentation resulted in an increase in the spinal cord dose, whereas use of a titanium cage had a minimal effect on dose distribution. While planning SBRT in patients with spinal reconstructions, avoidance of the rod and preventing interaction between the rod and beam might be the optimal solution for preventing unexpectedly high spinal cord doses.

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.

Spinal arteriovenous shunts: accuracy of shunt detection, localization, and subtype discrimination using spinal magnetic resonance angiography and manual contrast injection using a syringe.

PubMed

Unsrisong, Kittisak; Taphey, Siriporn; Oranratanachai, Kanokporn

2016-04-01

The object of this study was to evaluate the accuracy of fast 3D contrast-enhanced spinal MR angiography (MRA) using a manual syringe contrast injection technique for detecting and evaluating spinal arteriovenous shunts (AVSs). This was a retrospective study of 15 patients and 20 spinal MRA and catheter angiography studies. The accuracy of using spinal MRA to detect spinal AVS, localize shunts, and discriminate the subtype and dominant arterial feeder of the AVS were studied. There were 14 pretherapeutic and 6 posttherapeutic follow-up spinal MRA and catheter spinal angiography studies. The spinal AVS was demonstrated in 17 of 20 studies. Spinal MRA demonstrated 100% sensitivity for detecting spinal AVS with no false-negative results. A 97% accuracy rate for AVS subtype discrimination and shunt level localization was achieved using this study's diagnostic criteria. The detection of the dominant arterial feeder was limited to 9 of these 17 cases (53%). The fast 3D contrast-enhanced MRA technique performed using manual syringe contrast injection can detect the presence of a spinal AVS, locate the shunt level, and discriminate AVS subtype in most cases, but is limited when detecting small arterial feeders.

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 ...

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.

Multichannel Detrended Fluctuation Analysis Reveals Synchronized Patterns of Spontaneous Spinal Activity in Anesthetized Cats

PubMed Central

Rodríguez, Erika E.; Hernández-Lemus, Enrique; Itzá-Ortiz, Benjamín A.; Jiménez, Ismael; Rudomín, Pablo

2011-01-01

The analysis of the interaction and synchronization of relatively large ensembles of neurons is fundamental for the understanding of complex functions of the nervous system. It is known that the temporal synchronization of neural ensembles is involved in the generation of specific motor, sensory or cognitive processes. Also, the intersegmental coherence of spinal spontaneous activity may indicate the existence of synaptic neural pathways between different pairs of lumbar segments. In this study we present a multichannel version of the detrended fluctuation analysis method (mDFA) to analyze the correlation dynamics of spontaneous spinal activity (SSA) from time series analysis. This method together with the classical detrended fluctuation analysis (DFA) were used to find out whether the SSA recorded in one or several segments in the spinal cord of the anesthetized cat occurs either in a random or in an organized manner. Our results are consistent with a non-random organization of the sets of neurons involved in the generation of spontaneous cord dorsum potentials (CDPs) recorded either from one lumbar segment (DFA- mean = 1.040.09) or simultaneously from several lumbar segments (mDFA- mean = 1.010.06), where  = 0.5 indicates randomness while 0.5 indicates long-term correlations. To test the sensitivity of the mDFA method we also examined the effects of small spinal lesions aimed to partially interrupt connectivity between neighboring lumbosacral segments. We found that the synchronization and correlation between the CDPs recorded from the L5 and L6 segments in both sides of the spinal cord were reduced when a lesion comprising the left dorsal quadrant was performed between the segments L5 and L6 (mDFA- = 0.992 as compared to initial conditions mDFA- = 1.186). The synchronization and correlation were reduced even further after a similar additional right spinal lesion (mDFA- = 0.924). In contrast to the classical methods, such as correlation and coherence quantification that define a relation between two sets of data, the mDFA method properly reveals the synchronization of multiple groups of neurons in several segments of the spinal cord. This method is envisaged as a useful tool to characterize the structure of higher order ensembles of cord dorsum spontaneous potentials after spinal cord or peripheral nerve lesions. PMID:22046288

Regulated viral BDNF delivery in combination with Schwann cells promotes axonal regeneration through capillary alginate hydrogels after spinal cord injury.

PubMed

Liu, Shengwen; Sandner, Beatrice; Schackel, Thomas; Nicholson, LaShae; Chtarto, Abdelwahed; Tenenbaum, Liliane; Puttagunta, Radhika; Müller, Rainer; Weidner, Norbert; Blesch, Armin

2017-09-15

Grafting of cell-seeded alginate capillary hydrogels into a spinal cord lesion site provides an axonal bridge while physically directing regenerating axonal growth in a linear pattern. However, without an additional growth stimulus, bridging axons fail to extend into the distal host spinal cord. Here we examined whether a combinatory strategy would support regeneration of descending axons across a cervical (C5) lateral hemisection lesion in the rat spinal cord. Following spinal cord transections, Schwann cell (SC)-seeded alginate hydrogels were grafted to the lesion site and AAV5 expressing brain-derived neurotrophic factor (BDNF) under control of a tetracycline-regulated promoter was injected caudally. In addition, we examined whether SC injection into the caudal spinal parenchyma would further enhance regeneration of descending axons to re-enter the host spinal cord. Our data show that both serotonergic and descending axons traced by biotinylated dextran amine (BDA) extend throughout the scaffolds. The number of regenerating axons is significantly increased when caudal BDNF expression is activated and transient BDNF delivery is able to sustain axons after gene expression is switched off. Descending axons are confined to the caudal graft/host interface even with continuous BDNF expression for 8weeks. Only with a caudal injection of SCs, a pathway facilitating axonal regeneration through the host/graft interface is generated allowing axons to successfully re-enter the caudal spinal cord. Recovery from spinal cord injury is poor due to the limited regeneration observed in the adult mammalian central nervous system. Biomaterials, cell transplantation and growth factors that can guide axons across a lesion site, provide a cellular substrate, stimulate axon growth and have shown some promise in increasing the growth distance of regenerating axons. In the present study, we combined an alginate biomaterial with linear channels with transplantation of Schwann cells within and beyond the lesion site and injection of a regulatable vector for the transient expression of brain-derived neurotrophic factor (BDNF). Our data show that only with the full combination axons extend across the lesion site and that expression of BDNF beyond 4weeks does not further increase the number of regenerating axons. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A clinical evaluation of four non-Luer spinal needle and syringe systems.

PubMed

Kinsella, S M; Goswami, A; Laxton, C; Kirkham, L; Wharton, N; Bowen, M

2012-11-01

We performed an evaluation of non-Luer spinal devices supplied by four manufacturers or suppliers: Polymedic; Pajunk; Sarstedt; and Smiths. For each supplier, 100 evaluations were performed using a 25-G 90-mm spinal needle, 3-ml syringe, 5-ml syringe and filter needle; for comparison, 100 evaluations were performed with our standard Luer equipment. The non-Luer devices were associated with more qualitative problems compared with the Luer devices, for example, poor feel of dural puncture (9-32% vs 10%, respectively), poor observation of cerebrospinal fluid in the hub (3-27% vs 0%), and connection problem of the syringe to the spinal needle (7-33% vs 0%). There was also more frequent failure to achieve the spinal injection due to equipment-related causes (4-7% vs 0%, respectively). Median (IQR [range]) numeric satisfaction scores for the spinal needles were: Luer 10 (9-10 [7-10]); Polymedic 7 (4-8 [0-10]; Pajunk 7 (5-8 [0-10]); Sarstedt 7 (6-8 [0-10]); and Smiths 9 (7-10 [0-10]) (p<0.0001). Satisfaction scores for all spinal equipment were: Luer 10 (9-10 [5-10]); Polymedic 8 (6-8 [0-10]); Pajunk 7 (5-7 [1-9]); Sarstedt 8 (6-8 [0-10]); and Smiths 8 (8-9 [2-10]) (p<0.0001). Between 21% and 75% of non-Luer evaluations were rated with satisfaction worse than the usual Luer needle compared with 0-10% rated better, depending on the needle type. Between 22% and 76% of non-Luer evaluations were rated with satisfaction worse than the usual Luer equipment compared with 0-14% rated better. Specific concerns included poor feel of tissue planes and observation of cerebrospinal fluid (Polymedic), difficulty with connection of the syringe to the spinal needle and trocar removal (Pajunk), poor feel of tissue planes and needle flexibility (Sarstedt) and difficulty with connection of the syringe to the spinal needle (Smiths). We could not demonstrate a short-term learning curve for the new devices. Decisions on purchasing and implementation of the new non-Luer equipment will have to acknowledge that clinicians may have greater technical problems and reduced satisfaction compared with the current equipment. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

Effect of locomotor training in completely spinalized cats previously submitted to a spinal hemisection.

PubMed

Martinez, Marina; Delivet-Mongrain, Hugo; Leblond, Hugues; Rossignol, Serge

2012-08-08

After a spinal hemisection in cats, locomotor plasticity occurring at the spinal level can be revealed by performing, several weeks later, a complete spinalization below the first hemisection. Using this paradigm, we recently demonstrated that the hemisection induces durable changes in the symmetry of locomotor kinematics that persist after spinalization. Can this asymmetry be changed again in the spinal state by interventions such as treadmill locomotor training started within a few days after the spinalization? We performed, in 9 adult cats, a spinal hemisection at thoracic level 10 and then a complete spinalization at T13, 3 weeks later. Cats were not treadmill trained during the hemispinal period. After spinalization, 5 of 9 cats were not trained and served as control while 4 of 9 cats were trained on the treadmill for 20 min, 5 d a week for 3 weeks. Using detailed kinematic analyses, we showed that, without training, the asymmetrical state of locomotion induced by the hemisection was retained durably after the subsequent spinalization. By contrast, training cats after spinalization induced a reversal of the left/right asymmetries, suggesting that new plastic changes occurred within the spinal cord through locomotor training. Moreover, training was shown to improve the kinematic parameters and the performance of the hindlimb on the previously hemisected side. These results indicate that spinal locomotor circuits, previously modified by past experience such as required for adaptation to the hemisection, can remarkably respond to subsequent locomotor training and improve bilateral locomotor kinematics, clearly showing the benefits of locomotor training in the spinal state.

Muscle twitching

MedlinePlus

... Some are common and normal. Others are signs of a nervous system disorder. Causes Causes may include: Autoimmune disorders , such ... muscle Spinal muscular atrophy Weak muscles (myopathy) Symptoms of a nervous system disorder include: Loss of, or change in, sensation ...