Les lésions médullaires traumatiques : épidémiologie et perspectives

AbstractObjectiveSpecify the epidemiological data on the acute spinal cord injuries and define a group of patients that could benefit from cellular transplantation therapy designed with the aim of repair and regeneration of damaged spinal cord tissues.Material and methodsFive years monocentric (Gui-de-Chauliac Hospital, Montpellier, France) retrospective analysis of patients suffering from spinal cord injury (SCI). Spinal cord injured-patients, defined as sensory-motor complete, underwent a clinical evaluation following American Spinal Injury Association (ASIA) and functional type 2 Spinal Cord Independence Measure (SCIM2) scorings as well as radiological evaluation through spinal cord magnetic resonance imaging (MRI).ResultsOne hundred and fifty-seven medical records were reviewed and we selected and re-examined 20 patients with complete thoracic spinal cord lesion. Clinical and radiological evaluations of these patients demonstrated, in 75 % of the cases, an absence of clinical progression after a mean of 49months. Radiological abnormalities were constantly present in the initial (at the admission to hospital) and control (re-evaluation) MRI and no reliable predictive criteria of prognosis had been found.Discussion/ConclusionWe compare our results to the literature and discuss advantages and limits of cellular transplantation strategies for these patients.RésuméObjectifsConnaître les données épidémiologiques de notre région sanitaire sur les traumatismes médullaires. Au sein de cette population, sélectionner les patients susceptibles de bénéficier de thérapie cellulaire dans la moelle épinière lésée dans l’objectif de régénérer le tissu nerveux. Évaluer à distance ces patients.Patients et méthodeAnalyse rétrospective de tous les patients pris en charge pour un traumatisme vertébro-médullaire. Réévaluation clinique et radiologique des patients présentant une atteinte médullaire thoracique sensitivomotrice complète. Réévaluation réalisée par le score de l’American Spinal Injury Association (ASIA), le score fonctionnel Type 2 Spinal Cord Independence Measure (SCIM2) et contrôle radiologique par une IRM médullaire.RésultatsCent cinquante-sept dossiers de patients ont été analysés et 28 patients présentaient une lésion médullaire complète. Une évaluation clinique et radiologique réalisée chez 20 patients sur 28 (71 %) a montré l’absence d’évolution clinique dans 75 % des cas dans un délai moyen de 49 mois. Les anomalies radiologiques étaient présentes dans 100 % des cas sur l’IRM initiale et de contrôle sans qu’aucun critère fiable prédictif de bon pronostic n’est retrouvé.Discussion/conclusionNous présentons ces résultats comparativement à ceux de la littérature et nous discutons chez ces malades les stratégies de transplantation cellulaire, leurs limites actuelles et les progrès nécessaires pour obtenir des résultats

Cervical spine injuries from diving accident: A 10-year retrospective descriptive study on 64 patients

SummaryIntroductionNinety percent of the lesions resulting from diving injuries affect the cervical spine and are potentially associated with spinal cord injuries. The objective is to determine the most frequent lesion mechanisms. Evaluate the therapeutic alternatives and the biomechanical evolution (kyphotic deformation) of diving-induced cervical spine injuries. Define epidemiological characteristics of diving injuries.Materials and methodsA retrospective analysis over a period of 10years was undertaken for patients admitted to the Department of Neurosurgery of Montpellier, France, with cervical spinal injuries due to a diving accident. Patients were re-evaluated and clinical and radiological evaluation follow-ups were done.ResultsThis study included 64 patients. Cervical spine injuries resulting from diving predominantly affect young male subjects. They represent 9.5% of all the cervical spine injuries. In 22% of cases, patients presented severe neurological troubles (ASIA A, B, C) at the time of admission. A surgical treatment was done in 85% of cases, mostly using an anterior cervical approach.DiscussionThis is a retrospective study (type IV) with some limitations. The incidence of diving injuries in our region is one of the highest as compared to reports in the literature. Despite an increase of our surgical indications, 55% of these cases end up with a residual kyphotic deformation but there is no relationship between the severity of late vertebral deformity and high Neck Pain and Disability Scale (NPDS) scores.Level of evidenceLevel IV, retrospective study

Anatomical study of serotonergic innervation and 5-HT1A receptor in the human spinal cord

Serotonergic innervation of the spinal cord in mammals has multiple roles in the control of motor, sensory and visceral functions. In rats, functional consequences of spinal cord injury at thoracic level can be improved by a substitutive transplantation of serotonin (5-HT) neurons or regeneration under the trophic influence of grafted stem cells. Translation to either pharmacological and/or cellular therapies in humans requires the mapping of the spinal cord 5-HT innervation and its receptors to determine their involvement in specific functions. Here, we have performed a preliminary mapping of serotonergic processes and serotonin-lA (5-HT1A) receptors in thoracic and lumbar segments of the human spinal cord. As in rodents and non-human primates, 5-HT profiles in human spinal cord are present in the ventral horn, surrounding motoneurons, and also contact their presumptive dendrites at lumbar level. 5-HT1A receptors are present in the same area, but are more densely expressed at lumbar level. 5-HT profiles are also present in the intermediolateral region, where 5-HT1A receptors are absent. Finally, we observed numerous serotonergic profiles in the superficial part (equivalent of Rexed lamina II) of the dorsal horn, which also displayed high levels of 5-HT1A receptors. These findings pave the way for local specific therapies involving cellular and/or pharmacological tools targeting the serotonergic system

Grafted Human Embryonic Progenitors Expressing Neurogenin-2 Stimulate Axonal Sprouting and Improve Motor Recovery after Severe Spinal Cord Injury

7 p.Background: Spinal cord injury (SCI) is a widely spread pathology with currently no effective treatment for any symptom. Regenerative medicine through cell transplantation is a very attractive strategy and may be used in different non-exclusive ways to promote functional recovery. We investigated functional and structural outcomes after grafting human embryonic neural progenitors (hENPs) in spinal cord-lesioned rats.Methods and Principal Findings: With the objective of translation to clinics we have chosen a paradigm of delayed grafting, i.e., one week after lesion, in a severe model of spinal cord compression in adult rats. hENPs were either naive or engineered to express Neurogenin 2 (Ngn2). Moreover, we have compared integrating and non-integrating lentiviral vectors, since the latter present reduced risks of insertional mutagenesis. We show that transplantation of hENPs transduced to express Ngn2 fully restore weight support and improve functional motor recovery after severe spinal cord compression at thoracic level. This was correlated with partial restoration of serotonin innervations at lumbar level, and translocation of 5HT1A receptors to the plasma membrane of motoneurons. Since hENPs were not detectable 4 weeks after grafting, transitory expression of Ngn2 appears sufficient to achieve motor recovery and to permit axonal regeneration. Importantly, we also demonstrate that transplantation of naive hENPs is detrimental to functional recovery.Conclusions and Significance: Transplantation and short-term survival of Ngn2-expressing hENPs restore weight support after SCI and partially restore serotonin fibers density and 5HT1A receptor pattern caudal to the lesion. Moreover, grafting of naive-hENPs was found to worsen the outcome versus injured only animals, thus pointing to the possible detrimental effect of stem cell-based therapy per se in SCI. This is of major importance given the increasing number of clinical trials involving cell grafting developed for SCI patients.This study was supported by the European Union FP6 "RESCUE" STREP; the "Institut pour la Recherche sur la Moelle Epiniere"; the "Academie de Medecine"; the "Societe Francaise de Neurochirurgie"; "Verticale" and the "Association Demain Debout Aquitaine". The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Pure cervical radiculopathy due to spontaneous spinal epidural haematoma (SSEH): report of a case solved conservatively

Introduction: Spontaneous spinal epidural haematoma (SSEH) is widely recognised throughout the literature as a cause of myelopathy, radicular compression being very rarely reported. Surgical management is almost always recommended, especially in the cases of spinal cord compression. Conservative treatment is reported as a curiosity and only in the case of spontaneous improvement. This report presents the particular case of a 64-year-old patient undergoing anticoagulant therapy that had a cervical radiculopathy due to a SSEH confirmed by MRI. The patient improved spontaneously and symptoms were solved with unconventional conservative treatment and without stopping the anticoagulant therapy. Conclusions: Spontaneous epidural haematoma must be kept in mind when patients undergoing anticoagulant therapy have a sudden onset of cervicobrachialgia. Even though most spinal surgeons advocate surgical treatment, a conservative approach may lead to a complete recovery and may be considered as a good option in the case of radicular involvement. Discontinuation of the anticoagulant therapy may not always be needed, especially when the clinical syndrome improves spontaneously

Conductive Cellulose Composites with Low Percolation Threshold for 3D Printed Electronics

We are reporting a 3D printable composite paste having strong thixotropic rheology. The composite has been designed and investigated with highly conductive silver nanowires. The optimized electrical percolation threshold from both simulation and experiment is shown from 0.7 vol. % of silver nanowires which is significantly lower than other composites using conductive nano-materials. Reliable conductivity of 1.19 × 102 S/cm has been achieved from the demonstrated 3D printable composite with 1.9 vol. % loading of silver nanowires. Utilizing the high conductivity of the printable composites, 3D printing of designed battery electrode pastes is demonstrated. Rheology study shows superior printability of the electrode pastes aided by the cellulose\u27s strong thixotropic rheology. The designed anode, electrolyte, and cathode pastes are sequentially printed to form a three-layered lithium battery for the demonstration of a charging profile. This study opens opportunities of 3D printable conductive materials to create printed electronics with the next generation additive manufacturing process

Spatio-Temporal Progression of Grey and White Matter Damage Following Contusion Injury in Rat Spinal Cord

Cellular mechanisms of secondary damage progression following spinal cord injury remain unclear. We have studied the extent of tissue damage from 15 min to 10 weeks after injury using morphological and biochemical estimates of lesion volume and surviving grey and white matter. This has been achieved by semi-quantitative immunocytochemical methods for a range of cellular markers, quantitative counts of white matter axonal profiles in semi-thin sections and semi-quantitative Western blot analysis, together with behavioural tests (BBB scores, ledged beam, random rung horizontal ladder and DigiGait™ analysis). We have developed a new computer-controlled electronic impactor based on a linear motor that allows specification of the precise nature, extent and timing of the impact. Initial (15 min) lesion volumes showed very low variance (1.92±0.23 mm3, mean±SD, n = 5). Although substantial tissue clearance continued for weeks after injury, loss of grey matter was rapid and complete by 24 hours, whereas loss of white matter extended up to one week. No change was found between one and 10 weeks after injury for almost all morphological and biochemical estimates of lesion size or behavioural methods. These results suggest that previously reported apparent ongoing injury progression is likely to be due, to a large extent, to clearance of tissue damaged by the primary impact rather than continuing cell death. The low variance of the impactor and the comprehensive assessment methods described in this paper provide an improved basis on which the effects of potential treatment regimes for spinal cord injury can be assessed

Endocrinologic, neurologic, and visual morbidity after treatment for craniopharyngioma

Craniopharyngiomas are locally aggressive tumors which typically are focused in the sellar and suprasellar region near a number of critical neural and vascular structures mediating endocrinologic, behavioral, and visual functions. The present study aims to summarize and compare the published literature regarding morbidity resulting from treatment of craniopharyngioma. We performed a comprehensive search of the published English language literature to identify studies publishing outcome data of patients undergoing surgery for craniopharyngioma. Comparisons of the rates of endocrine, vascular, neurological, and visual complications were performed using Pearson’s chi-squared test, and covariates of interest were fitted into a multivariate logistic regression model. In our data set, 540 patients underwent surgical resection of their tumor. 138 patients received biopsy alone followed by some form of radiotherapy. Mean overall follow-up for all patients in these studies was 54 ± 1.8 months. The overall rate of new endocrinopathy for all patients undergoing surgical resection of their mass was 37% (95% CI = 33–41). Patients receiving GTR had over 2.5 times the rate of developing at least one endocrinopathy compared to patients receiving STR alone or STR + XRT (52 vs. 19 vs. 20%, χ2P < 0.00001). On multivariate analysis, GTR conferred a significant increase in the risk of endocrinopathy compared to STR + XRT (OR = 3.45, 95% CI = 2.05–5.81, P < 0.00001), after controlling for study size and the presence of significant hypothalamic involvement. There was a statistical trend towards worse visual outcomes in patients receiving XRT after STR compared to GTR or STR alone (GTR = 3.5% vs. STR 2.1% vs. STR + XRT 6.4%, P = 0.11). Given the difficulty in obtaining class 1 data regarding the treatment of this tumor, this study can serve as an estimate of expected outcomes for these patients, and guide decision making until these data are available