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Concept: Paraplegia


Brain-machine interfaces (BMIs) provide a new assistive strategy aimed at restoring mobility in severely paralyzed patients. Yet, no study in animals or in human subjects has indicated that long-term BMI training could induce any type of clinical recovery. Eight chronic (3-13 years) spinal cord injury (SCI) paraplegics were subjected to long-term training (12 months) with a multi-stage BMI-based gait neurorehabilitation paradigm aimed at restoring locomotion. This paradigm combined intense immersive virtual reality training, enriched visual-tactile feedback, and walking with two EEG-controlled robotic actuators, including a custom-designed lower limb exoskeleton capable of delivering tactile feedback to subjects. Following 12 months of training with this paradigm, all eight patients experienced neurological improvements in somatic sensation (pain localization, fine/crude touch, and proprioceptive sensing) in multiple dermatomes. Patients also regained voluntary motor control in key muscles below the SCI level, as measured by EMGs, resulting in marked improvement in their walking index. As a result, 50% of these patients were upgraded to an incomplete paraplegia classification. Neurological recovery was paralleled by the reemergence of lower limb motor imagery at cortical level. We hypothesize that this unprecedented neurological recovery results from both cortical and spinal cord plasticity triggered by long-term BMI usage.

Concepts: Spinal cord, Sensory system, Sense, Somatosensory system, Spinal cord injury, Virtual reality, Proprioception, Paraplegia


Spinal cord injuries disrupt bidirectional communication between the patient’s brain and body. Here, we demonstrate a new approach for reproducing lower limb somatosensory feedback in paraplegics by remapping missing leg/foot tactile sensations onto the skin of patients' forearms. A portable haptic display was tested in eight patients in a setup where the lower limbs were simulated using immersive virtual reality (VR). For six out of eight patients, the haptic display induced the realistic illusion of walking on three different types of floor surfaces: beach sand, a paved street or grass. Additionally, patients experienced the movements of the virtual legs during the swing phase or the sensation of the foot rolling on the floor while walking. Relying solely on this tactile feedback, patients reported the position of the avatar leg during virtual walking. Crossmodal interference between vision of the virtual legs and tactile feedback revealed that patients assimilated the virtual lower limbs as if they were their own legs. We propose that the addition of tactile feedback to neuroprosthetic devices is essential to restore a full lower limb perceptual experience in spinal cord injury (SCI) patients, and will ultimately, lead to a higher rate of prosthetic acceptance/use and a better level of motor proficiency.

Concepts: Skin, Sense, Somatosensory system, Spinal cord injury, Virtual reality, Proprioception, Human leg, Paraplegia


Cell transplantation in patients suffering spinal cord injury (SCI) is in its initial stages, but currently there is confusion about the results because of the disparity in the techniques used, the route of administration, and the criteria for selecting patients.

Concepts: Pharmacology, Medicine, Spinal cord, Clinical trial,, Spinal cord injury, Paraplegia


Excessive reliance on wheelchairs in individuals with tetraplegia or paraplegia due to spinal cord injury (SCI) leads to many medical co-morbidities, such as cardiovascular disease, metabolic derangements, osteoporosis, and pressure ulcers. Treatment of these conditions contributes to the majority of SCI health care costs. Restoring able-body-like ambulation in this patient population can potentially reduce the incidence of these medical co-morbidities, in addition to increasing independence and quality of life. However, no biomedical solution exists that can reverse this loss of neurological function, and hence novel methods are needed. Brain-computer interface (BCI) controlled lower extremity prostheses may constitute one such novel approach.

Concepts: Health care, Medicine, Health, Disease, Illness, Spinal cord injury, Ibn al-Nafis, Paraplegia


Background/Aims: To describe the epidemiology of spinal cord injury (SCI) in the developing world. Methods: Developing countries were selected based on the definition proposed by the International Monetary Fund. A literature search was performed in July 2012 in Medline and Embase. Further article procurement was obtained via the reference lists of the identified articles, websites, and direct contact with the authors of the identified studies. We designed search strategies using the key words: SCI, epidemiology, incidence, and prevalence. According to the inclusion criteria, 64 studies from 28 countries were included. Results: The incidence of SCI in developing countries is 25.5/million/year (95% CI: 21.7-29.4/million/year) and ranges from 2.1 to 130.7/million/year. Males comprised 82.8% (95% CI: 80.3-85.2) of all SCIs with a mean age of 32.4 years (95% CI: 29.7-35.2). The two leading causes of SCI were found to be motor vehicle crashes (41.4%; 95% CI: 35.4-47.4) and falls (34.9%; 95% CI: 26.7-43.1). Complete SCIs were found to be more common than incomplete injuries (complete SCI: 56.5%; 95% CI: 47.6-65.3; incomplete SCI: 43.0%; 95% CI: 34.1-52.0). Similarly, paraplegia was found to be more common than tetraplegia (paraplegia: 58.7%; 95% CI: 51.5-66.0; tetraplegia: 40.6%; 95% CI: 33.3-48.0). Conclusion: Through an understanding of the epidemiology of SCI in developing countries, appropriate preventative strategies and resource allocation may decrease the incidence and improve the care of these injuries.

Concepts: Incidence, Developing country, Spinal cord injury, World Bank, Brazil, United Nations, Paraplegia, International Monetary Fund


OBJECTIVE:Numerous studies in animals have shown the unique property of olfactory ensheathing cells tostimulate regeneration of lesioned axons in the spinal cord. In a Phase I clinical trial, weassessed the safety and feasibility of transplantation of autologous mucosal olfactoryensheathing cells and olfactory nerve fibroblasts in patients with complete spinal cord injury.METHODS:Six patients with chronic thoracic paraplegia (American Spinal Injury Association class AASIA A) were enrolled for the study. Three patients were operated and three served as acontrol group. The trial protocol consisted of pre- and postoperative neuro-rehabilitation,olfactory mucosal biopsy, culture of olfactory ensheathing cells, and intraspinal cell grafting.Patient’s clinical state was evaluated by clinical, neurophysiological and radiological tests.RESULTS:There were no adverse findings related to olfactory mucosa biopsy or transplantation of olfactory ensheathing cells at one year after surgery. There was no evidence of neurologicaldeterioration, neuropathic pain, neuroinfection or tumorigenesis. In one cell-grafted patient an asymptomatic syringomyelia was observed. Neurological improvement was observed only intransplant recipients. The first 2 operated patients improved from ASIA A to ASIA C andASIA B. Diffusion tensor imaging showed restitution of continuity of some white mattertracts throughout the focus of spinal cord injury in these patients. The third operated patientalthough remained ASIA A, showed improved motor and sensory function of the first spinalcords segments below the level of injury. Neurophysiological examinations showedimprovement in spinal cord transmission and activity of lower extremity muscles in surgicallytreated patients but not in patients receiving only neuro-rehabilitation.CONCLUSIONS:Observations at 1 year indicate that the obtaining, culture and intraspinal transplantation ofautologous olfactory ensheathing cells was safe and feasible. The significance of theneurological improvement in the transplant recipients and the extent to which the celltransplants contributed to it will require larger numbers of patients.

Concepts: Spinal cord, Pain, Olfactory bulb, Olfactory system, Spinal cord injury, Imaging, Paraplegia, Antenna


Cooling strategies that help prevent a reduction in exercise capacity whilst exercising in the heat have received considerable research interest over the past 3 decades, especially in the lead up to a relatively hot Olympic and Paralympic Games. Progressing into the next Olympic/Paralympic cycle, the host, Rio de Janeiro, could again present an environmental challenge for competing athletes. Despite the interest and vast array of research into cooling strategies for the able-bodied athlete, less is known regarding the application of these cooling strategies in the thermoregulatory impaired spinal cord injured (SCI) athletic population. Individuals with a spinal cord injury (SCI) have a reduced afferent input to the thermoregulatory centre and a loss of both sweating capacity and vasomotor control below the level of the spinal cord lesion. The magnitude of this thermoregulatory impairment is proportional to the level of the lesion. For instance, individuals with high-level lesions (tetraplegia) are at a greater risk of heat illness than individuals with lower-level lesions (paraplegia) at a given exercise intensity. Therefore, cooling strategies may be highly beneficial in this population group, even in moderate ambient conditions (~21 °C). This review was undertaken to examine the scientific literature that addresses the application of cooling strategies in individuals with an SCI. Each method is discussed in regards to the practical issues associated with the method and the potential underlying mechanism. For instance, site-specific cooling would be more suitable for an athlete with an SCI than whole body water immersion, due to the practical difficulties of administering this method in this population group. From the studies reviewed, wearing an ice vest during intermittent sprint exercise has been shown to decrease thermal strain and improve performance. These garments have also been shown to be effective during exercise in the able-bodied. Drawing on additional findings from the able-bodied literature, the combination of methods used prior to and during exercise and/or during rest periods/half-time may increase the effectiveness of a strategy. However, due to the paucity of research involving athletes with an SCI, it is difficult to establish an optimal cooling strategy. Future studies are needed to ensure that research outcomes can be translated into meaningful performance enhancements by investigating cooling strategies under the constraints of actual competition. Cooling strategies that meet the demands of intermittent wheelchair sports need to be identified, with particular attention to the logistics of the sport.

Concepts: Method acting, Spinal cord injury, Ablative brain surgery, Strategy, Lesion, Rio de Janeiro, Paraplegia, Paralympic Games


OBJECTIVE:: To investigate the link between infection-related risk factors for cerebral palsy subtypes in children born at term. METHODS:: A case-control study was performed in a population-based series of children with cerebral palsy born at term (n=309) matched with a control group (n=618). The cases were divided into cerebral palsy subtypes: spastic hemiplegia, spastic diplegia, spastic tetraplegia, and dyskinetic cerebral palsy. All forms of spastic cerebral palsy were also analyzed together. All records were examined for maternal and neonatal signs of infection. Univariate and adjusted analyses were performed. RESULTS:: Infection-related risk factors were shown to be independent risk factors for spastic cerebral palsy in the adjusted analyses. This was especially pronounced in the subgroup with spastic hemiplegia in which bacterial growth in urine during pregnancy (n=11 [7.5%], odds ratio [OR] 4.7, 95% confidence interval [CI] 1.5-15.2), any infectious disease during pregnancy (n=57 [39.0%], OR 2.9, 95% CI 1.7-4.8), severe infection during pregnancy (n=12 [8.2%], OR 15.4, 95% CI 3.0-78.1), antibiotic therapy once during pregnancy (n=33 [22.6%], OR 6.3, 95% CI 3.0-15.2) as well as several times during pregnancy (n=9 [6.2%], OR 15.6, 95% CI 1.8-134.2) constituted strong independent risk factors. However, only neonatal infection (n=11 [9.1%], OR 14.7, 95% CI 1.7-126.5) was independently significantly associated with an increased risk of spastic diplegia and tetraplegia. CONCLUSIONS:: Infection-related factors are strong independent risk factors for the subgroup with spastic hemiplegia in children with cerebral palsy born at term. The finding is less pronounced in the subgroups with spastic diplegia or tetraplegia. LEVEL OF EVIDENCE:: II.

Concepts: Pregnancy, Epidemiology, Infectious disease, Infection, Cerebral palsy, Spastic diplegia, Spasticity, Paraplegia


BACKGROUND The aim of this study was to explore the relationship between the α2-HS glycoprotein concentrations in serum and the occurrence of neurogenic heterotopic ossification (NHO) in patients with spinal cord injury (SCI). MATERIAL AND METHODS During the period between January 2011 and January 2012, 75 patients (67 male) with paraplegia caused by spinal cord injury were enrolled. The patients were divided into 2 groups in accordance with the occurrence of heterotopic ossification based on the results high-frequency ultrasound on the bilateral hip joint. The levels of α2-HS glycoprotein, C-reactive protein (CRP), D-dimer, and bone morphogenetic protein (BMP) were detected by ELISA. RESULTS We found a significant decrease of α2-HS glycoprotein in SCI patients with NHO compared to SCI patients without NHO. In contrast, a significant elevation of serum calcium, D-dimer, BMP, and CRP was observed in SCI patients with NHO. The degree of maturity of NHO did not influence the level of α2-HS glycoprotein. Multivariate liner regression analysis showed that the level of serum α2-HS glycoprotein was correlated with CRP and spasticity. CONCLUSIONS The decreased level of α2-HS glycoprotein may be related to the formation of neurogenic heterotopic ossification in patients with spinal cord injury. Our results suggest that α2-HS glycoprotein might be a risk factor for NHO in patients with SCI.

Concepts: Antibody, Regression analysis, Bone, Neuron, Hip, C-reactive protein, Spinal cord injury, Paraplegia


The aim of this study was to investigate upper airway anatomy in quadriplegics with obstructive sleep apnea. Fifty subjects were recruited from three hospitals in Australia: people with quadriplegia due to spinal cord injury and obstructive sleep apnea (n = 11), able-bodied people with obstructive sleep apnea (n = 18), and healthy, able-bodied controls (n = 19). All underwent 3-Tesla magnetic resonance imaging of their upper airway. A subgroup (n = 34) received a topical vasoconstrictor, phenylephrine and post-phenylephrine magnetic resonance imaging. Mixed-model analysis indicated no significant differences in total airway lumen volume between the three groups (P = 0.086). Spinal cord injury-obstructive sleep apnea subjects had a significantly larger volume of soft palate (P = 0.020) and retroglossal lateral pharyngeal walls (P = 0.043) than able-bodied controls. Able-bodied-obstructive sleep apnea subjects had a smaller mandible volume than spinal cord injury-obstructive sleep apnea subjects and able-bodied control subjects (P = 0.036). No differences were seen in airway length between groups when controlling for height (P = 0.055). There was a marginal increase in velopharyngeal volume across groups post-phenylephrine (P = 0.050), and post hoc testing indicated the difference was confined to the able-bodied-obstructive sleep apnea group (P < 0.001). No other upper airway structures showed significant changes with phenylephrine administration. In conclusion, people with obstructive sleep apnea and quadriplegia do not have a structurally smaller airway than able-bodied subjects. They did, however, have greater volumes of soft palate and lateral pharyngeal walls, possibly due to greater neck fat deposition. The acute response to upper airway topical vasoconstriction was not enhanced in those with obstructive sleep apnea and quadriplegia. Changes in upper airway anatomy likely contribute to the high incidence in obstructive sleep apnea in quadriplegic subjects.

Concepts: Nuclear magnetic resonance, Magnetic resonance imaging, Sleep apnea, Obstructive sleep apnea, Paralysis, Paraplegia, Quadriplegia, Soft palate