Effects of Different Doses of Mesenchymal Stem Cells on Functional Recovery After Compressive Spinal-Cord Injury in Mice.

Despite advances in technology and rehabilitation, no effective therapies are available for patients with SCI, which remains a major medical challenge. This study compared the efficacy of 3 different doses of mesenchymal stem cells (MSCs) administered by intraperitoneal injection as a therapeutic strategy for compressive SCI. We used adult female C57BL/6 mice that underwent laminectomy at the T9 level, followed by spinal-cord compression for 1 min with a 30-g vascular clip. The animals received an intraperitoneal (i.p.) injection of MSCs (8 × 104, 8 × 105 or 8 × 106 in 500 µl) or DMEM (500 µl), one week after SCI. The cells of the three MSC doses administered i.p. were able to migrate to the injury site, increase local expression of trophic factors, and enhance fiber sparing and/or regeneration, accompanied by substantial improvement in locomotor performance. Cell transplantation at 8 × 105 density showed the best therapeutic potential, leading to significant tissue and functional improvements compared to the other two doses. These findings indicate that i.p. application of MSCs at the density of 8 × 105 yielded the best results, suggesting that this dose is a good choice for SCI treatment.

A highly reproducible mouse model of compression spinal cord injury.

Experimental spinal cord injury (SCI) can maintain the continuity of the spinal cord, as in the contusion (e.g., weight-fall) or compression models, or not, when there is a partial or a complete transection. The majority of acute human SCI is not followed by complete transection, but there is a combination of contusion, compression, and possibly partial transection. The method described here is a compressive mouse model that presents a combination of contusion and compression components and has many facilities in its execution. This lesion was established by our group and represents a simple, reliable, and inexpensive clip compression model with functional and morphological reproducibility. In this chapter we describe, step by step, the protocol of this experimental SCI.

New approach for graded compression spinal cord injuries in Rhesus macaque: method feasibility and preliminary observations.

BACKGROUND: Current models of spinal cord injury (SCI) have been ineffective for translational research. Primate blunt SCI, which more closely resembles human injury, could be a promising model to fill this gap. METHODS: Graded compression SCI was produced by inflating at T9 an epidural balloon as a function of spinal canal dimensions in a non-uniform group of monkeys. RESULTS: Sham injury and cord compression by canal invasion of 50-75% produced minimal morpho-functional alterations, if at all. Canal invasion of 90-100% resulted in proportional functional deficits. Unexpectedly, these animals showed spontaneous gradual recovery over a 12-week period achieving quadruped walking, although with persistent absence of foot grasping reflex. Histopathology revealed predominance of central cord damage that correlated with functional status. CONCLUSIONS: Our preliminary results suggest that this model could potentially be a useful addition to translational work, but requires further validation by including animals with permanent injuries and expansion of replicates.

Human dental pulp cells: a new source of cell therapy in a mouse model of compressive spinal cord injury.

Strategies aimed at improving spinal cord regeneration after trauma are still challenging neurologists and neuroscientists throughout the world. Many cell-based therapies have been tested, with limited success in terms of functional outcome. In this study, we investigated the effects of human dental pulp cells (HDPCs) in a mouse model of compressive spinal cord injury (SCI). These cells present some advantages, such as the ease of the extraction process, and expression of trophic factors and embryonic markers from both ecto-mesenchymal and mesenchymal components. Young adult female C57/BL6 mice were subjected to laminectomy at T9 and compression of the spinal cord with a vascular clip for 1 min. The cells were transplanted 7 days or 28 days after the lesion, in order to compare the recovery when treatment is applied in a subacute or chronic phase. We performed quantitative analyses of white-matter preservation, trophic-factor expression and quantification, and ultrastructural and functional analysis. Our results for the HDPC-transplanted animals showed better white-matter preservation than the DMEM groups, higher levels of trophic-factor expression in the tissue, better tissue organization, and the presence of many axons being myelinated by either Schwann cells or oligodendrocytes, in addition to the presence of some healthy-appearing intact neurons with synapse contacts on their cell bodies. We also demonstrated that HDPCs were able to express some glial markers such as GFAP and S-100. The functional analysis also showed locomotor improvement in these animals. Based on these findings, we propose that HDPCs may be feasible candidates for therapeutic intervention after SCI and central nervous system disorders in humans.

Is there a difference between narrowing of the spinal canal and neurological deficits comparing Denis and Magerl classifications?

STUDY DESIGN: Retrospective chart review. OBJECTIVES: The objective of the current study was to evaluate the correlation between neurological deficits and the severity of narrowing of the spinal canal in patients with thoracic, thoracolumbar and lumbar burst-type fractures by comparing the classifications of Denis and Magerl. From 1989 to 2005, a total of 227 patients with burst fractures following Denis' criteria were studied. SETTING: Tertiary teaching institution. METHODS: Computed tomographic scans of the fractured spine were analyzed to assess the narrowing of the spinal canal. Following Magerl's criteria, patients were later subdivided into two groups according to the presence of associated ligament injuries, out of which 185 patients had no such injuries and the remaining 42 patients were classified as Megerl group B. RESULTS: Results were evaluated based on the initial neurological status of patients according to Frankel and based on the midsagittal diameter of the fractured vertebra. A significant correlation was found between the narrowing of the spinal canal and neurological deficits in both classifications, with no significant differences between either. CONCLUSION: The percentage of narrowing of the spinal canal proved to be a pre-disposing factor for the severity of the neurological status in thoracolumbar and lumbar burst-type fractures according to the classifications of Denis and Magerl. The greater the bone fragment in the spinal canal, the greater will be the probability of neurological deficits in both fracture classifications, equally.

Predifferentiated embryonic stem cells promote functional recovery after spinal cord compressive injury.

We tested the effects of mouse embryonic stem cells (mES) grafts in mice spinal cord injury (SCI). Young adult female C57/Bl6 mice were subjected to laminectomy at T9 and 1-minute compression of the spinal cord with a vascular clip. Four groups were analyzed: laminectomy (Sham), injured (SCI), vehicle (DMEM), and mES-treated (EST). mES pre-differentiated with retinoic acid were injected (8 x 10(5) cells/2 microl) into the lesion epicenter, 10 min after SCI. Basso mouse scale (BMS) and Global mobility test (GMT) were assessed weekly up to 8 weeks, when morphological analyses were performed. GMT analysis showed that EST animals moved faster (10.73+/-0.9076, +/-SEM) than SCI (5.581+/-0.2905) and DMEM (5.705+/-0.2848), but slower than Sham animals (15.80+/-0.3887, p<0.001). By BMS, EST animals reached the final phase of locomotor recovery (3.872+/-0.7112, p<0.01), while animals of the SCI and DMEM groups improved to an intermediate phase (2.037+/-0.3994 and 2.111+/-0.3889, respectively). White matter area and number of myelinated nerve fibers were greater in EST (46.80+/-1.24 and 279.4+/-16.33, respectively) than the SCI group (39.97+/-0.925 and 81.39+/-8.078, p<0.05, respectively). EST group also presented better G-ratio values when compared with SCI group (p<0.001). Immunohistochemical revealed the differentiation of transplanted cells into astrocytes, oligodendrocytes, and Schwann cells, indicating an integration of transplanted cells with host tissue. Ultrastructural analysis showed, in the EST group, better tissue preservation and more remyelination by oligodendrocytes and Schwann cells than the other groups. Our results indicate that acute transplantation of predifferentiated mES into the injured spinal cord increased the spared white matter and number of nerve fibers, improving locomotor function.

Effectiveness of calcitonin in intermittent claudication treatment of patients with lumbar spinal stenosis: a systematic review.

STUDY DESIGN: Systematic review. OBJECTIVE: Analyze the level of evidence in the effectiveness of calcitonin on the treatment of neurogenic claudication in patients with lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA: One of the most disabling features of lumbar spinal stenosis is neurogenic claudication. There have been proposed different drug therapies for it. The recommendation for calcitonin use in these patients has been sustained on autocontrolled clinical trial (Streifler et al, Neurol Neurosurg Psychiatry 1989;52:543-4), which only included 6 patients. MATERIAL AND METHOD: We performed a search on electronic databases that included Medline and Embase; we recovered 10 original articles, of which only 4 fulfilled the RCT criteria. These articles were reviewed independent and blinded way by 6 previously capacitated reviewers to extract data and score a quality of them by the criteria of Cochrane Handbook (1996) with maximum score of 1.00 and minimum score of 0.33. RESULTS: Score quality vary in the 4 articles: Porter and Millar, Spine 1988;13:1061-4 (score, 0.68), Eskola et al, Calcif Tissue Int 1992;50:400-3 (score, 0.88), Podichetty et al, Spine 2004;29:2343-9 (score, 0.88), and Tafazal et al, Eur Spine J 2007;16:207-12 (score, 0.92). Due to the great heterogenicity observed (sample sizes, selection criteria, doses, frequency, and duration of calcitonin, and outcome measurements), we were unable to perform a meta-analysis. Only one of these studies (Porter and Millar, Spine 1988;13:1061-4; score, 0.68) found favorable results for the use of calcitonin compared with placebo; of the 3 remaining trials none found significative evidence between drug therapy and placebo. CONCLUSION: The present data suggest that calcitonin administration in the treatment for neurogenic claudication has no benefit in patients with lumbar spinal stenosis.

Adamantinoma of the spine: case report.

OBJECTIVE: We report a patient with a cervicothoracic spinal and a mandibular adamantinoma. Adamantinoma is a rare malignant neoplasm of bone and, to our knowledge, there have been only five cases of spinal adamantinoma reported. The pathogenesis of the adamantinoma, as well as the management of this extremely rare spinal tumor, is reviewed. CLINICAL PRESENTATION: A 55-year-old man was admitted to our service with cervical pain and signs of C8 and T1 radiculopathy. On physical examination, cervical spine deformity, swelling in the left mandible region, and signs of C8 and T1 radiculopathy were observed. Neuroradiology examinations showed an osteolytic mass of the C6, C7, and T1 vertebral bodies, extending into the lateral masses and transverse processes. After surgical procedures, the patient had clinical improvement. INTERVENTION: Corpectomy of C6, C7, and T1 was performed through a cervicothoracic anterior approach. Anterior stabilization of the spine was obtained using an autologous iliac crest graft and osteosynthesis with an anterior plate. On a second procedure, posterior tumor resection and spinal stabilization were performed. After the 1-year follow-up examination, a new anterior procedure was performed because of tumor recidivity and spine instability. CONCLUSION: Adamantinoma, an extremely rare lesion, is a locally aggressive tumor with slow growth and the potential to metastasize. Although it is an extremely rare occurrence in the spine, adamantinoma should be considered on the diagnosis of tumors of the vertebrae. Neuroradiological examinations are not specific in the differentiation of this tumor from other conditions. This fact, coupled with the limited experience that most physicians in general have in dealing with this tumor, makes the diagnosis and treatment of adamantinoma challenging.

Cervical spondylotic myelopathy: 10 years of prospective outcome analysis of anterior decompression and fusion.

BACKGROUND: Fifty-one patients with cervical spondylotic myelopathy (CSM) treated by anterior cervical corpectomy with fusion (ACWF) at our institution were included in a study during a period of 10 years to evaluate neurological, anatomical, and functional outcomes including satisfaction levels. METHODS: We have completed a prospective evaluation of 39 patients with spondylotic myelopathy submitted to ACWF during the period of 1989-2000. The data were analyzed for age, duration of symptoms, severity of preoperative neurological deficit, and single-level or multilevel compressive status looking for possible association with prognostic surrogate data and clinical outcome that were evaluated with the Nurick score and a survey of level of satisfaction. RESULTS: Of the 51 patients, 39 fullfilled the intended follow-up being 28 men (71.8%) and 11 women (28.2%). The average age was 63.5 years. Duration of symptoms ranged from 1 to 240 months (mean, 38.1 months). The mean preoperative Nurick scale score was 2.97; the mean postoperative score was 2.1. The most frequently involved vertebral body was C5 (71.7%). The follow-up period was longer than 18 months for all patients. Postoperative nonneurological complications occurred in 8 patients (15.6%). The mortality rate was 1.9% (n = 1). Postoperative results showed improvement in 25 patients (64.1%), no change in 13 (33.3%), and worsening in 1 (2.6%). The correlation coefficient of preoperative and postoperative Nurick scores was 0.733 (R(2) = 0.53). Of the 39 patients, 31 answered the questionnaire for quality of life-19 (61.2%) were very satisfied, 6 were satisfied (19.35%), and 6 were not satisfied (19.35%). CONCLUSION: Most patients (80.6%) were very satisfied or satisfied with the outcome and would decide again for the surgery (87%) if the results were previously known. Anterior cervical corpectomy with fusion was a reliable and rewarding procedure for CSM, with functional improvement in most patients. Excellent long-term outcome results in cervical fusion can be achieved without the use of hardware instrumentation.

Aplicación de la técnica de manejo de la arteria vertebral en la exéresis de un neurinoma espinal C2-C3 de difícil resolución quirúrgica / Transforaminal exceresis of a C2-C3 anterolateral extending spinal neurinoma exposing the vertebral artery

Se presenta el caso de un paciente con un neurinoma espinal C2-C3 de ubicación anterolateral, intra y extracanalicular, con gran compresión medular, que no pudo ser resuelto por la vía tradicional posterior por su alta vascuralización y adherencia a los planos adyacentes, debiendo utilizarse en él un abordamiento anterolateral con exposición y manejo de la arteria vertebral y la exéresis transforaminal del neurinoma con excelentes resultados quirúrgicos y clínicos en el paciente, el cual fue reincorporado a su vida normal a los dos meses de su intervención

Sintomatología, diagnóstico y resultados del tratamiento de los síndromes agudos de compresión medular / Symptomatology, diagnosis and results of treatment in acute spinal cord compression syndromes

Los síndromes agudos de compresión medular en la gran mayoría de los casos (88 por ciento) se deben a tumores espinales, de los cuales dos tercios corresponden a metástasis. El 76 por ciento de los casos presentan un período prodrómico previo a la aparición de déficit neurológicos, caracterizados por dolores, mientras que sólo pocos casos inician su sintomatología con trastornos de la función motora o sensitiva. Aparte de las radiografías simples de columna y la mielografía, la tomografía computarizada y la resonancia magnética ocupan hoy en día una posición destacada en el diagnóstico de esta enfermedad. Independientemente del hecho si se trata de un tumor primario o una metástasis los resultados operatorios son más favorables en aquellos casos que presentan los menores déficit preoperatorios, lo cual subraya la importancia de una interpretación cuidadosa de los síntomas iniciales

Spinal cord injury syndrome with motor sparing in the absence of all sensation.

This paper describes the anatomic basis for the unusual presentation in a spinal cord injured subject of preservation of motor power in the absence of all sensation. The patient was examined at four hours, and daily thereafter, after a motorcycle accident in which he was thrown over the handle bars. He had trace ankle dorsi and plantar flexors, but light touch, pin, position, and vibratory sensation were absent below the level of C4 bilaterally. There was no physical evidence to differentiate whether he suffered a flexion or extension injury. Cervical spine films showed no evidence of fracture or dislocation, but anterior and posterior osteophytes involving C3 to C4, C4 to C5, and C5 to C6 were present. Magnetic resonance imaging showed evidence of cervical cord edema at C3 to C4 with possible hemorrhage and severe spinal stenosis at C3 to C4 and C4 to C5. This patient received a compression injury with resulting classic anterior spinal artery syndrome. Because of his spinal stenosis with a decreased anterior-posterior (AP) diameter of the canal, the posterior circulation was also compromised. The extensive pial anastomotic network provided relative sparing of the most peripheral components of the lateral corticospinal tracts. This case report demonstrates a unique clinical picture that cannot be anatomically classified by current American Spinal Injury Association (ASIA) standards as central cord syndrome. It can be explained by the lamination of the ascending and descending tracts in relation to the vascular supply of the cervical cord in conjunction with the narrowing of the AP diameter of the canal due to spinal stenosis.

Cervicomedullary compression in young patients with achondroplasia: value of comprehensive neurologic and respiratory evaluation.

We studied prospectively 26 young patients with achondroplasia to test two hypotheses: that respiratory problems may be the result of occult spinal cord compression, and that achondroplastic patients with cord compression might have occult respiratory abnormalities. Respiratory abnormalities were present in 85%, the majority caused by a primary problem of the pulmonary system, such as small thoracic cage or obstructed airway. Three patients had hypoxemia, recurrent cyanotic spells, and episodes of respiratory distress explainable only by cervicomedullary cord compression; in each patient, respiratory problems were alleviated by decompressive surgery. Another six patients with cervicomedullary compression had, in addition, at least one primary pulmonary cause of respiratory problems. After decompressive surgery the respiratory problems improved in three and were unchanged in three. Reconstructed sagittal CT images proved the most sensitive technique for detecting craniocervical stenosis as a cause of cervicomedullary cord compression, although some degree of stenosis was present in nearly all of the patients.