No abstract

The potential of adult mesenchymal stem cells (MSCs) to differentiate towards cartilage, bone, adipose tissue, or muscle is well established. However, the capacity of MSCs to differentiate towards intervertebral disc (IVD)-like cells is unknown. The aim of this study was to compare the molecular phenotype of human IVD cells and articular chondrocytes and to analyze whether mesenchymal stem cells can differentiate towards both cell types after transforming growth factor β (TGFβ)-mediated induction in vitro.Bone marrow-derived MSCs were differentiated in spheroid culture towards the chondrogenic lineage in the presence of TGFβ 3 , dexamethasone, and ascorbate. A customized cDNA-array comprising 45 cartilage-, bone-, and stem cell-relevant genes was used to quantify gene expression profiles.After TGFβ-mediated differentiation, MSC spheroids turned positive for collagen type II protein and expressed a large panel of genes characteristic for chondrocytes, including aggrecan, decorin, fibromodulin, and cartilage oligomeric matrix protein, although at levels closer to IVD tissue than to hyaline articular cartilage. Like IVD tissue, the spheroids were strongly positive for collagen type I and osteopontin. MSC spheroids expressed more differentiation markers at higher levels than culture-expanded IVD cells and chondrocytes, which both dedifferentiated in monolayer culture.In conclusion, mesenchymal stem cells adopted a gene expression profile that resembled native IVD tissue more closely than native joint cartilage. Thus, these cells may represent an attractive source from which to obtain IVD-like cells, whereas modification of culture conditions is required to approach the molecular phenotype of chondrocytes in hyaline cartilage. 2005;23:403-411 Stem Cells

ATI335 was well tolerated in humans; efficacy trials using intrathecal antibody administration may be considered in acute SCI.

Background/Objective: To compare symptoms of neurogenic bowel dysfunction in patients with spinal cord injury (SCI) at baseline and after 10 weeks of treatment with transanal irrigation and to identify possible factors that could predict outcome of the treatment. Methods: Sixty-two patients with SCI (45 men and 17 women; mean age, 47.5 6 15.5 [SD] years) from 5 specialized European SCI centers were offered treatment with transanal irrigation for a 10-week period. Bowel function was assessed at baseline and at termination using the Cleveland Clinic Constipation Scoring System (CCCSS; 0-30, 30 ¼ severe symptoms), St. Mark's Fecal Incontinence Grading System (FIGS; 0-24, 24 ¼ severe symptoms), and the Neurogenic Bowel Dysfunction score (NBD; 0-47, 47 severe symptoms). Factors predicting improvement in bowel function scores were identified using a general linear model. Results: Severity of symptoms at termination was significantly reduced compared with baseline values (CCCSS: À3.4; 95% confidence interval [CI], À4.6 to À2.2; FIGS:-4.1; 95% CI, À5.2 to À2.9; NBD: À4.5; 95% CI, À6.6 to À2.4; all P , 0.0001). Although several factors were associated with positive outcome, no consistent and readily explainable pattern could be identified. Surprisingly, hand function, level of dependency, predominant symptom, and colonic transit time were not associated with outcome. Conclusions: Transanal irrigation in patients with SCI reduces constipation, improves anal continence, and improves symptom-related quality of life. No readily obtainable factors could predict outcome, which might be because of the relatively low number of patients. This supports the use of trial and error as a strategy in deciding on a bowel management method for neurogenic bowel dysfunction.

The association of cervical spinal cord injury and swallowing disorders is clinically well recognized. This study was performed to determine the clinical significance and the outcome of deglutition disorders observed in the initial treatment of cervical spinal cord injury in our tertiary care spinal cord injury unit. All patients with cervical spinal cord injury admitted to our facility for initial care between January 1997 and December 2000 were included in our study. Prevalence of dysphagia and frequency of pneumonia were determined. An assessment of deglutition at discharge was performed. Dysphagia was diagnosed in 26 of the 73 patients with cervical spinal cord injury. Tracheostomy and duration of orotracheal intubation are associated with dysphagia. The disorder necessitated dietary restrictions in 18 patients. Six of these patients had to be discharged with a percutaneous enterogastric feeding tube; seven had persistent problems not resulting in dietary restrictions. The incidence of late pneumonia was significantly increased with two associated deaths. Dysphagia is a serious complication associated with prolonged requirement for ventilatory support. Patients have to be monitored closely because the incidence of pneumonia is increased. While the situation improves for most patients, a significant number of patients need a percutaneous enterogastric feeding tube as a permanent solution.

BackgroundParameters of MR imaging play a pivotal role in diagnosing lumbar spinal stenosis (LSS), and serve as an important tool in clinical decision-making. Despite the importance of MR imaging, little is known about the correlation between MRI parameters, objective gait analysis, and clinical presentation of patients with lumbar spinal stenosis.MethodsSixty-three patients from our clinic with symptomatic lumbar spinal stenosis leading to neurogenic claudication were included in this study in accordance with clearly defined inclusion and exclusion criteria. Clinical parameters, the depression status (CES-D), the subjective functional back capacity (FFbH-R), and the absolute walking distance (treadmill gait analysis) were quantitatively evaluated in correlation with morphological data from radiographs and MRI scans, in order to determine the coherence of spinal canal narrowing and clinical affliction.ResultsSixty-three consecutive paents with a median age of 68 years and a mean Body Mass Index (BMI) of 28 were included in the study. The mean FFbH-R score displayed a value of 44 percent. The depression status scored an average of 13.6. Objectively measured walking distances showed a mean value of 172 m until patients stopped due to leg pain. A significant difference was found between the objectively measured and the subjectively estimated walking distance. The mean cross-sectional area of the dural tube at L1/2 was 113 mm2, at L2/3 94 mm2, at L3/4 73 mm2, at L4/5 65 mm2, and at L5/S1 93 mm2. The mean overall cross sectional area of the dural tube of all segments did not correlate with the objectively measured walking distance. However, bivariate analysis found that the BMI (tau b = -0.194), functional back capacity (tau b = -0.225), and the cross sectional area of the dural tube at L1/2 (tau b = -0.188) correlated significantly with the objectively measured walking distance.ConclusionAccording to the results of this study MRI findings failed to show a major clinical relevance when evaluating the walking distance in patients with lumbar spinal stenosis and, therefore, should be treated with some caution as a predictor of walking distance. In determining the disease pattern of spinal stenosis functional back capacity and BMI might play a more active role than previously thought.

BackgroundNeurogenic bladder dysfunction represents one of the most common and devastating sequelae of traumatic spinal cord injury (SCI). As early prediction of bladder outcomes is essential to counsel patients and to plan neurourological management, we aimed to develop and validate a model to predict urinary continence and complete bladder emptying 1 y after traumatic SCI.Methods and FindingsUsing multivariate logistic regression analysis from the data of 1,250 patients with traumatic SCI included in the European Multicenter Spinal Cord Injury study, we developed two prediction models of urinary continence and complete bladder emptying 1 y after traumatic SCI and performed an external validation in 111 patients. As predictors, we evaluated age, gender, and all variables of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) and of the Spinal Cord Independence Measure (SCIM). Urinary continence and complete bladder emptying 1 y after SCI were assessed through item 6 of SCIM. The full model relies on lower extremity motor score (LEMS), light-touch sensation in the S3 dermatome of ISNCSI, and SCIM subscale respiration and sphincter management: the area under the receiver operating characteristics curve (aROC) was 0.936 (95% confidence interval [CI]: 0.922–0.951). The simplified model is based on LEMS only: the aROC was 0.912 (95% CI: 0.895–0.930). External validation of the full and simplified models confirmed the excellent predictive power: the aROCs were 0.965 (95% CI: 0.934–0.996) and 0.972 (95% CI 0.943–0.999), respectively. This study is limited by the substantial number of patients with a missing 1-y outcome and by differences between derivation and validation cohort.ConclusionsOur study provides two simple and reliable models to predict urinary continence and complete bladder emptying 1 y after traumatic SCI. Early prediction of bladder function might optimize counselling and patient-tailored rehabilitative interventions and improve patient stratification in future clinical trials.

Twenty nine spinal cord injury patients were treated by resection of heterotopic ossi®cation in 41 hips. The average follow-up period after surgery was 4.2 years. The mean time to surgery after injury was 82.1 months. The indications for surgery were seating problems, loss of function, pressure sores and pain. The average preoperative motion in¯exion and extension was 21.958, the average intraoperative motion was 94.518. The average motion at follow-up evaluation was 82.688. Clinical relevant recurrence occurred in three patients. Complications excluding recurrence occurred in 10 hips, including deep and super®cial wound infections, fracture, aneurysm and pressure ulcer. The operation was followed by a speci®c regime of physiotherapy and radiation therapy.