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Todd J Albert

Publications and source records attributed to Todd J Albert.

At least 37 records · Page 2Linked to original sources
PubMed2006

Anatomy of the percutaneous presacral space for a novel fusion technique.

OBJECTIVES: Lumbar fusion has been widely used to treat unstable spinal disorders. Methods are evolving from open procedures to less invasive methods to avoid soft tissue trauma. Recently, a soft tissue sparing method to access the axial lumbosacral spine has been developed. It is crucial to determine structures potentially at risk for injury during this fusion technique. The anatomy of the presacral space and safety of the paracoccygeal approach were evaluated through cadaveric dissection and radiographic studies. The objective was to evaluate the safety of a paracoccygeal approach to the axial lumbosacral spine and determine structures that could potentially be injured. METHODS: The paracoccygeal approach was performed on two cadavers, followed by dissection. Distances from the midline trajectory of the approach to surrounding vascular structures were determined. Similar distances were also measured on computed tomography (CT) and magnetic resonance imaging (MRI) of 12 patients, as well as CT images of two additional patients. A "safe zone" was determined using the sagittal length of the presacral space and the distance between the most medial internal iliac vessel on the right and left, respectively. RESULTS: The coronal safe zone averaged 6.9 and 6.0 cm on MRI and CT, respectively. The mean distance from the anterior sacral margin to the rectum at the S3-S4 level was 1.2 and 1.3 cm on MRI and CT, respectively. CONCLUSION: In this study, we defined the "coronal safe zone" within the presacral space. This "safe zone" may guide surgeons when utilizing the percutaneous paracoccygeal approach.

Cadaver↗
PubMed2005

Comparison of OP-1 Putty (rhBMP-7) to iliac crest autograft for posterolateral lumbar arthrodesis: a minimum 2-year follow-up pilot study.

STUDY DESIGN: A prospective, randomized, controlled, multicenter clinical study. OBJECTIVE: To compare the safety and clinical and radiographic outcomes of OP-1 (BMP-7) Putty to autogenous iliac crest bone graft in a population of patients undergoing laminectomy and posterolateral fusion for symptomatic lumbar stenosis associated with degenerative spondylolisthesis. SUMMARY OF BACKGROUND DATA: Although the existing preclinical and clinical data suggest that OP-1 is able to achieve osteoinduction and clinical fusion in a variety of situations, the efficacy of this recombinant protein in a clinical spine fusion population has not been fully elucidated. This study directly compares the efficacy and safety of OP-1 putty to autograft bone for arthrodesis in patients with symptomatic stenosis in association with degenerative spondylolisthesis. METHODS: Thirty-six patients with degenerative lumbar spondylolisthesis and symptoms of neurogenic claudication underwent laminectomy, bilateral medial facetectomy, and posterolateral fusion using either iliac crest autograft or OP-1 Putty. Oswestry scores and SF-36 questionnaires were used to determine the clinical response to treatment. Independent, blinded neuroradiologists reviewed both static and dynamic radiographs to determine the fusion status. Successful fusion was declared whenthe presence of continuous bridging bone between the transverse processes was observed and less than 5 degrees of angular motion and 2 mm of translational movement was measured using digital calipers. RESULTS: Efficacy data were tabulated for 27 patients at the 24-month time point and an additional 4 patients (without evaluable 24-month results) at the 36-month time point. One patient was not evaluable for radiology, so the data reflect clinical information for 31 patients and radiology for 30 patients. Clinical success, defined as a 20% improvement in the preoperative Oswestry score, was achieved by 17 of 20 (85%) OP-1 Putty patients and 7 of 11 (64%) autograft patients. A successful posterolateral fusion was achieved in 11 of 20 (55%) OP-1 Putty patients and 4 of 10 (40%) autograft patients. SF-36 scores showed similar clinical improvement in both groups. No systemic toxicity, ectopic bone formation, recurrent stenosis, or other adverse events specifically related to the use of the OP-1 Putty implant were observed. CONCLUSION: This study represents the first clinical trial to demonstrate the safety and similarity of OP-1 Putty as a replacement for autogenous bone graft in the posterolateral fusion environment with a minimum of 2-year follow-up. OP-1 Putty was able to achieve osteoinduction leading to a radiographically solid fusion in the absence of autogenous iliac crest bone graft in 55% of the patients at 24 and 36 months. These results compare favorably to the historical fusion rates reported for uninstrumented arthrodesis in this challenging clinical scenario.

Adult↗
PubMed2005

Dysphagia after anterior cervical decompression and fusion: prevalence and risk factors from a longitudinal cohort study.

STUDY DESIGN: Retrospective analysis of the incidence and prevalence of dysphagia after anterior cervical decompression and fusion (ACDF). OBJECTIVES: To examine the incidence and prevalence of dysphagia after ACDF, determine possible associated patient and procedural characteristics, and examine dysphagia's impact on long-term health status and function. SUMMARY OF BACKGROUND DATA: Dysphagia is a common early complaint after ACDF, but the risk factors associated with its development are not understood. METHODS: Telephone surveys (Cervical Spine Outcomes Questionnaire) and clinical assessments (Oswestry Neck Disability Scale and SF-36) were used to evaluate 454 patients who had undergone ACDF at one of 23 nationwide sites for individual and procedure characteristics that might contribute to dysphagia. RESULTS: Of the 454 patients, 30% reported dysphagia at the 3-month assessment (incident cases). The incidence of new complaints of dysphagia at each follow-up point was 29.8%, 6.9%, and 6.6% at 3, 6, and 24 months, respectively. Dysphagia persisted at 6 and 24 months in 21.5% and 21.3% of patients, respectively. The risk of dysphagia increased with number of surgical vertebral levels at 3 months: 1 level, 42 of 212 (19.8%); 2 levels, 50 of 150 (33.3%); 3+ levels, 36 of 92 (39.1%). Patients reporting dysphagia at 3 months had a significantly higher self-reported disability and lower physical health status at subsequent assessments. CONCLUSION: Duration of preexisting pain and the number of vertebral levels involved in the surgical procedure appear to influence the likelihood of dysphagia after ACDF.

Aged↗
PubMed2005

Hypoxia activates MAPK activity in rat nucleus pulposus cells: regulation of integrin expression and cell survival.

OBJECTIVE: The aim of the present study was to investigate whether activation of MAPK subtypes ERK and p38 influences integrin expression and promotes nucleus pulposus cell survival in hypoxia. SUMMARY OF BACKGROUND DATA: We have recently shown that in a low oxygen environment, rat nucleus pulposus cells activate phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways. However, the role of these signaling pathways in regulating cell matrix interactions is not known. METHODS: Rat nucleus pulposus cells were cultured in hypoxia (2% O2) or normoxia (20% O2). Western blotting and kinase assay were used to analyze expression of MAPK signaling molecules. Cell attachment to collagen was studied using an adhesion assay, whereas flow cytometry and RT-PCR were performed to quantify integrin receptor expression. RESULTS: In a hypoxic environment (2% O2), rat nucleus pulposus cells showed a persistent phosphorylation of p38 and ERK proteins; pERK catalyzed the phosphorylation of Elk1-Gst fusion protein. When ERK activity was blocked, cell adhesion to Type II collagen, one of the major extracellular matrix proteins in the nucleus pulposus tissue, was impaired. A similar inhibitory effect on collagen adhesion was observed when nucleus pulposus cells were treated with an antibody to alpha2 integrin. Furthermore, when ERK activity was inhibited, there was a decrease in alpha2 integrin mRNA expression. In contrast to ERK, inhibition of p38 activity did not modulate alpha2 integrin subunit mRNA expression. Likewise, inhibition of ERK, but not p38, resulted in downregulation of nucleus pulposus alpha2 integrin protein levels and blocked cell survival in hypoxia. CONCLUSIONS: Hypoxia activated MAPK signaling pathway activity in nucleus pulposus cells. ERK, but not p38, regulated alpha2 integrin expression and cell survival.

Animals↗
PubMed2005

Cellular therapy for disc degeneration.

STUDY DESIGN: Review article regarding the developing field of cellular therapies for symptomatic disc degeneration. OBJECTIVE: To review the rationale and discuss the results of cellular strategies that have been proposed or investigated for disc degeneration. SUMMARY OF BACKGROUND DATA: Disc degeneration is a substantial clinical problem. Disc degeneration begins with a loss of disc cells and alterations in the extracellular matrix of the disc. One promising approach for this problem involves the use of cells transplanted to the degenerative disc to achieve functional tissue repair. METHODS: The rationale for using cellular therapy for disc degeneration is discussed. The basic science studies involving cellular transplantation to the disc are reviewed and future directions of this line of research are discussed. RESULTS: Although substantial work remains, the future of cellular therapies for symptomatic disc degeneration appears promising. CONCLUSION: Continued research is warranted to further define the optimal cell type, scaffolds, and adjuvants that will allow successful disc repair in human patients.

Animals↗
PubMed2005

Acute quadriplegia following closed traction reduction of a cervical facet dislocation in the setting of ossification of the posterior longitudinal ligament: case report.

STUDY DESIGN: A case report of acute quadriplegia resulting from closed traction reduction of traumatic bilateral cervical facet dislocation in a 54-year-old male with concomitant ossification of the posterior longitudinal ligament (OPLL). OBJECTIVES: To report an unusual presentation of a spinal cord injury, examine the approach to reversal of the injury, and review the treatment and management controversies of acute cervical facet dislocations in specific patient subgroups. SUMMARY OF BACKGROUND DATA: The treatment of acute cervical facet dislocations is an area of ongoing controversy, especially regarding the question of the necessity of advanced imaging studies before closed traction reduction of the dislocated cervical spine. The safety of an immediate closed, traction reduction of the cervical spine in awake, alert, cooperative, and appropriately select patients has been reported in several studies. To date, there have been no permanent neurologic deficits resulting from awake, closed reduction reported in the literature. A case of temporary, acute quadriplegia with complete neurologic recovery following successful closed traction reduction of a bilateral cervical facet dislocation in the setting of OPLL is presented. METHODS: The clinical neurologic examination, radiographic, and advanced imaging studies before and after closed, traction reduction of a cervical facet dislocation are evaluated and discussed. A review of the literature regarding the treatment of acute cervical facet dislocations is presented. RESULTS: Radiographs showed approximately 50% subluxation of the fifth on the sixth cervical vertebrae, along with computerized tomography revealing extensive discontinuous OPLL. The cervical facet dislocation was successfully reduced with an awake, closed traction reduction, before magnetic resonance imaging (MRI) evaluation. The patient subsequently had acute quadriplegia develop, with the ensuing MRI study illustrating severe spinal stenosis at the C5, C6 level as a result of OPLL or a large extruded disc herniation. Following an immediate anterior decompression and a posterior stabilization procedure, the patient regained full motor and sensory function. CONCLUSIONS: This case report highlights the advantages and shows some safety concerns regarding immediate, closed traction reduction of cervical facet dislocation with real-time neural monitoring in an awake, alert, oriented, and appropriately select patient before MRI studies in the setting of preexisting central stenosis from OPLL.

Acute Disease↗
PubMed2005

Failure of standard imaging to detect a cervical fracture in a patient with ankylosing spondylitis.

STUDY DESIGN: Retrospective case study of 38-year-old male with ankylosing spondylitis who presented with a Brown-Séquard syndrome following a fall and an occult fracture on initial spinal imaging studies. OBJECTIVE: To review the recommended imaging protocol in a patient with ankylosing spondylitis and a suspected cervical spine fracture. SUMMARY OF BACKGROUND DATA: Plain radiographic imaging using orthogonal views can detect the majority of spinal fractures. However, fracture identification is particularly difficult in patients with ankylosing spondylitis. Of the various contemporary imaging methods, [magnetic resonance imaging (MRI), computed tomography (CT), nuclear scanning] high-definition multidetector CT scanning is the most useful in identifying subtle fractures, but in metabolic bone diseases the utility of these methods is unknown. METHODS: Retrospective radiographic evaluation of imaging studies of ankylosing spondylitis patient with occult fracture by five spine surgeons and neuroradiologists, followed with detailed review and interpretation of literature concerning present radiology techniques and methods to isolate occult fractures. RESULTS: Initial imaging studies, including plain radiographs of the spinal axis, cervical and thoracic single-detector CT with reconstructed images, and MRI, were unremarkable in detecting an occult cervical spine fracture in a patient with ankylosing spondylitis and a spinal cord injury following a fall. The patient was placed empirically in a halo orthosis and a high definition multidetector CT scan was obtained. This study demonstrated a transverse fracture through the fused C6-C7 spinal level. CONCLUSION: Occult fractures in ankylosing spondylitis may not be apparent on routine plain radiographic and MRI studies. In the setting of ankylosing spondylitis, a high index of suspicion must be maintained in all patients presenting with spinal pain following even minor trauma. High-resolution multidetector CT imaging appears to be more sensitive and accurate in the diagnosis of fractures in this patient subgroup than other contemporary imaging methods.

Adult↗
PubMed2005

Industry support and correlation to study outcome for papers published in Spine.

STUDY DESIGN: Retrospective review of articles published in the journal Spine. OBJECTIVES: To evaluate potential correlations between research sponsorship and study outcome. SUMMARY OF BACKGROUND DATA: Industry sponsorship has traditionally been associated with more positive results than non-funded or peer-reviewed funded projects in other areas of medicine. The association of such sponsorship and study outcome has not been addressed previously in spine research. METHODS: Articles from the journal Spine from January 2002 to July 2003 were reviewed. These were examined for the subject evaluated, type of study design, funding source, and conclusion reached. RESULTS: Of 1143 articles, 527 met inclusion criteria of having abstract, materials/methods, and conclusion sections. Industry support was reported for 84 (15.9%), foundation support for 67 (12.7%), government support for 54 (10.2%), institution support for 17 (3.2%), and no funding was reported for 304 (57.9%). The odds ratio of industry funded reporting positive results was 3.3 times that of studies with any other funding sources (P < 0.001). CONCLUSIONS: Industry funded studies demonstrated a statistically greater likelihood to report positive results than studies with other funding sources. Potential explanations for this are biased study design, biased experimental technique, biased result interpretation, or publication bias. Although the expense of research and limited funding sources have forced an increased reliance on industry support for funding basic science and clinical spine research, this does introduce the potential for bias and must be recognized by the reader.

Bibliometrics↗
PubMed2005

Nucleus pulposus cells upregulate PI3K/Akt and MEK/ERK signaling pathways under hypoxic conditions and resist apoptosis induced by serum withdrawal.

STUDY DESIGN: To examine the impact of hypoxia, rat nucleus pulposus cells were maintained in monolayer culture in 2% O2 and survival and signal transduction pathways identified. OBJECTIVE: To elucidate the signaling pathways that allow nucleus pulposus cells to adapt to low oxygen environment. SUMMARY OF BACKGROUND DATA: Mammalian cell function is critically dependent on a continuous supply of oxygen. Interestingly, some specialized cell types that include nucleus pulposus cells of the intervertebral disc reside in a hypoxic environment. However, the mechanism of their adaptation to this low oxygen environment is not known. METHODS: Rat nucleus pulposus cells were harvested from explant cultures and grown to confluence in monolayer. Cells from passage 3-7 were maintained under hypoxia (2% O2) and normoxia (20% O2) for various time periods in complete or serum-free medium. Cells were also treated with pharmacologic agents that block PI3K and MAPK signaling pathways. Cell survival was assessed by MTT assay, annexinV-PI dual-color flow cytometry, and the TUNEL procedure. Expression of signaling proteins was evaluated by Western blot analysis. Cell phenotype was studied by semiquantitative RT-PCR. RESULTS: Under hypoxic conditions, rat nucleus pulposus cells were resistant to apoptosis induced by serum starvation. Protection was also observed after treatment of the nucleus cells by desferrioxamine, a compound that mimics many of the effects of hypoxia. Cell survival in hypoxia was related to activation of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways. Induction of Akt activation and ERK1/2 activationunder hypoxic condition was detected at 12 hours and correlated with inactivation of glycogen synthase kinase-3beta (GSK-3beta), an effector protein involved in regulation of apoptosis. Finally, inhibition of PI3K/Akt and MEK/ERK pathway using the inhibitors LY294002 and PD98059, respectively, impaired cell survival. CONCLUSION: It is concluded that under hypoxic conditions, rat nucleus pulposus cells are adapted for survival by regulation of expression of critical genes, downregulation of apoptosis through activation of the PI3K/Akt and MAPK survival pathways.

Animals↗
PubMed2005

Adult low-grade acquired spondylolytic spondylolisthesis: evaluation and management.

STUDY DESIGN: Literature review. OBJECTIVE: To discuss the presentation and evaluation of adult patients with acquired spondylolytic spondylolisthesis of low-grade severity and to review surgical treatment options. SUMMARY OF BACKGROUND DATA: Low-grade adult acquired spondylolytic spondylolisthesis is one of the most common forms of spondylolisthesis. METHODS: Literature review. RESULTS: Adults with symptomatic low-grade spondylolytic spondylolisthesis are treated predominantly nonoperatively, with activity modification, physiotherapy, nonsteroidal anti-inflammatory agents, and local injections. Surgical treatment is reserved for individuals with intractable back pain and/or radicular symptoms. A number of surgical options exist, including direct pars repair, and fusion with or without decompression. Fusion can be achieved by providing anterior column support alone, posterior support alone, or a combined circumferential approach; the optimal method by which fusion should be achieved has not been established. CONCLUSIONS: The management of low-grade acquired spondylolytic spondylolisthesis requires a thoughtful and individualized approach, recognizing the frequently benign natural history of the deformity and the potentially good clinical outcomes from surgery in those select patients with intolerable back and leg pain. While fusion is the mainstay of surgical management, a prospective randomized study would be extremely useful to delineate the optimal fusion technique.

Adult↗
PubMed2005

Differences in the work-up and treatment of conditions associated with low back pain by patient gender and ethnic background.

STUDY DESIGN: Retrospective review comparing physician workup of degenerative lumbosacral pathologies between different genders and ethnic groups. OBJECTIVES: To investigate whether patient ethnicity and gender influence the workup and treatment of degenerative spinal pathologies. SUMMARY OF BACKGROUND DATA: Data from numerous studies suggest that patient gender and ethnicity play a role in medical decision-making, with white males receiving more frequent interventions than women and minorities. METHODS: Patients enrolled for an "initial visit" in the National Spine Network database with lumbosacral level degenerative diagnosis were reviewed. Variables included patient gender, ethnicity, age, duration of symptoms, patient-graded severity of symptoms, radicular symptom pattern, and work status. RESULTS: We identified 5690 patients with degenerative lumbosacral pathologies. Although females were more likely than males to have imaging tests ordered, male (18.5%) patients were significantly more likely to have surgery recommended than female (16.3%) patients (P < 0.031). Nonwhite females were 52% less likely to have surgery offered at initial visit, as compared to white males (P < 0.005). More imaging tests were ordered or reviewed among whites (76.6%) than among any other ethnic group (P = 0.162). White (18.3%) and Asian (22.5%) patients were significantly more likely to have surgery recommended or prescribed than black (11.1%) and Hispanic (14.5) patients (P < 0.0001). CONCLUSIONS: This study suggests that ethnicity and gender affect the workup and surgical management of degenerative spinal disorders. However, it should be noted that there are a number of confounding factors not identified in the database, including managed care and insurance status and cultural differences, which may affect both test ordering and treatment recommendations. Further study of bias in clinical decision-making is indicated to assure equal delivery of quality care.

Black or African American↗
PubMed2005

A 2-year follow-up pilot study evaluating the safety and efficacy of op-1 putty (rhbmp-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions.

The ability of bone morphogenetic proteins (BMPs) to induce bone formation has led to a multitude of investigations into their use as bone graft substitutes in spinal surgery. The purpose of this multi-center clinical pilot study was to evaluate the safety and efficacy of BMP-7 (osteogenic protein 1, OP-1), in the form of a putty, combined with autograft for intertransverse process fusion of the lumbar spine in patients with symptomatic spinal stenosis and degenerative spondylolisthesis following spinal decompression. Twelve patients with spinal stenosis and degenerative lumbar spondylolisthesis underwent a laminectomy and partial or complete medial facetectomy as required for decompression of the neural elements, followed by an intertransverse process fusion by placing iliac crest autograft and OP-1 putty between the decorticated transverse processes. No instrumentation was used. Patients were followed clinically using the Oswestry scale and SF-36 outcome forms, and radiographically using static and dynamic radiographs to assess their fusion status over a 2-year period. Independent and blinded radiologists assessed the films for the presence of bridging bone between the transverse processes and measured translation and angulation on dynamic films using digital calipers. Radiographic outcome was compared to a historical control (autograft alone fusion without instrumentation for the treatment of degenerative spondylolisthesis). All adverse events were recorded prospectively. The results showed eight of the nine evaluable patients (89%) obtained at least a 20% improvement in their preoperative Oswestry score, while five of ten patients (50%) with radiographic follow-up achieved a solid fusion by the criteria used in this study. Bridging bone on the anteroposterior film was observed in seven of the ten patients (70%). No systemic toxicity, ectopic bone formation, recurrent stenosis or other adverse events related to the OP-1 putty implant were observed. A successful fusion was observed in slightly over half the patients in this study, using stringent criteria without adjunctive spinal instrumentation. This study did not demonstrate the statistical superiority of OP-1 combined with autograft over an autograft alone historical control, in which the fusion rate was 45%. There were no adverse events related to the OP-1 putty implant in this study, which supports findings in other studies suggesting the safety of bone morphogenetic proteins in spinal surgery.

Aged↗
PubMed2005

A critical analysis of the literature regarding surgical approach and outcome for adult low-grade isthmic spondylolisthesis.

OBJECTIVE: A systematic review of the radiographic and clinical outcomes of adult patients undergoing surgery for low-grade isthmic spondylolisthesis was performed to determine whether conclusions could be made regarding the optimal choice of surgically managing adult low-grade isthmic spondylolisthesis. METHODS: We tabulated the radiographic and clinical outcomes of patients who underwent a posterior procedure alone, an anterior procedure alone, or a combined anterior and posterior procedure. We also evaluated the influence of covariates such as laminectomy, spinal internal fixation, smoking, and secondary gain issues on these outcomes. Patients were pooled, and a chi analysis was performed to determine the relationship between surgical approach and patient outcome. A covariate analysis was performed to determine the influence of a laminectomy, spinal fixation, smoking, and secondary gain issues on these outcomes. RESULTS: The available literature consisted primarily of retrospective case series, with only 4 of 34 reports being prospective randomized controlled studies. Patients with combined anterior and posterior procedures were most likely to achieve a solid fusion and a successful clinical outcome. The use of spinal fixation also increased the chance of fusion and successful clinical outcome. CONCLUSIONS: A pooling of the surgical literature on adult low-grade spondylolisthesis indicates that a combined anterior and posterior procedure most reliably achieves fusion and a successful clinical outcome. The literature, however, is primarily retrospective and heterogeneous with respect to indications for surgery and methods of evaluating outcome, providing a compelling rationale for a prospective randomized controlled trial of the various surgical approaches to this problem.

Adult↗
PubMed2005

Timing of surgical stabilization after cervical and thoracic trauma. Invited submission from the Joint Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2004.

Appropriate timing for surgical intervention following destabilizing cervical or thoracic spine trauma remains controversial. Clinical investigators have failed to provide convincing evidence that the timing of surgery significantly affects neurological outcome in most situations. Nevertheless, early surgical stabilization of the injured spine has been shown to provide significant nonneurological benefits such as more rapid patient mobilization, facilitation of treating associated injuries, reduction in rates of pulmonary and pressure sore complications, reduction in duration of intensive care unit and hospital stays, and a decrease in overall medical costs. The findings of basic science studies have improved our understanding of the molecular and cellular events surrounding initial and secondary spinal cord injury (SCI), and analysis of these findings suggests that the early postinjury period may present a unique opportunity for meaningful intervention. This possibility has been supported by results obtained in animal studies that demonstrate the potential for improving functional outcome when surgical intervention is performed within a few hours following experimental SCI. Despite the absence of significant neurological recovery in most clinical studies, the results of most recent clinical studies strongly support the overall clinical benefits of early surgical intervention, particularly in the setting of unstable thoracic spinal column injury with associated SCI. Based on the best available scientific and clinical evidence, the authors report that it is therefore recommended that surgical stabilization be performed in as timely a fashion as possible, particularly for unstable thoracic spine trauma, within the constraints of the patient's overall medical condition and availability of appropriate resources.

Cervical Vertebrae↗
PubMed2005

Nonsurgical and surgical management of lumbar spinal stenosis.

The symptoms associated with lumbar spinal stenosis can decrease quality of life and may cause patients to seek treatment. Except in rare cases of rapid neurologic progression or cauda equina syndrome, nonsurgical modalities should be the initial treatment choice. Activity modification, a variety of medications, epidural steroid injections, and other methods are recommended for pain reduction. A formal physical therapy program, which focuses on flexion-based exercises, may lead to improved patientfunction. Surgery is indicated in patients who remain symptomatic despite a course of nonsurgical therapy and who have advanced imaging studies that correspond to existing .symptoms. Adequate decompression of the neural elements and maintenance of bony stability are necessary for a good surgical outcome for patients with spinal stenosis. Laminectomy has long been the method of choice for thorough lumbar decompression. Preserving at least the lateral half of the facet joints bilaterally and bone in the area of the pars interarticularis minimizes the potential for iatrogenic instability. Numerous other decompression techniques have been described, including multilevel laminotomies, fenestration, distraction laminoplasty, and microscopic decompression. Arthrodesis, either with or without instrumentation, is also indicated in some patients. Several studies report that surgical treatment produces better outcomes than nonsurgical treatment in the short term; however, the results tend to deteriorate with time. Lumbar decompressive surgery can be complicated by epidural hematoma, deep venous thrombosis, dural tear, infection, nerve root injury, and recurrence of symptoms.

Decompression, Surgical↗
PubMed2004

Differentiation of mesenchymal stem cells towards a nucleus pulposus-like phenotype in vitro: implications for cell-based transplantation therapy.

OBJECTIVE: Because mesenchymal stem cells can differentiate into chondrocyte-like cells, we ask the question, can mesenchymal stem cells commit to the nucleus pulposus phenotype? BACKGROUND: Back pain, a significant source of morbidity in our society, is linked to degenerative changes of the intervertebral disc. Absence of suitable graft tissue limits therapeutic approaches for repair of disc tissue. For this reason, there is considerable interest in developing "tissue engineering" strategies for the regeneration of the nucleus pulposus. METHODS: Rat mesenchymal stem cells were immobilized in 3-dimensional alginate hydrogels and cultured in a medium containing transforming growth factor-beta1 under hypoxia (2% O2) and normoxia (20% O2). Mesenchymal stem cells were examined by confocal microscopy to evaluate their viability and metabolic status after labeling with Celltracker green, a thiol sensitive dye, and Mitotracker red, a dye sensitive to the mitochondrial membrane potential. Flow cytometry, semiquantitative reverse transcription polymerase chain reaction and Western blot analysis were carried out to evaluate phenotypic and biosynthetic activities and the signaling pathways involved in the differentiation process. RESULTS: Under hypoxic conditions, mesenchymal stem cells formed large aggregates and exhibited positive Celltracker and Mitotracker signals. Glucose transporter-3, matrix metalloproteinase-2, collagen type II and type XI, and aggrecan mRNA and protein expression was upregulated, whereas there was no change in the levels of decorin, biglycan, fibromodulin, and lumican. Hypoxia maintained the expression of CD44 (hyaluronan receptor), ALCAM (CD166), and endoglin (transforming growth factor-beta receptor). Likewise, expression of beta3 and alpha2 integrin was upregulated. Transforming growth factor-beta treatment increased MAPK activity and Sox-9, aggrecan, and collagen type II gene expression. Basal levels of the phosphorylated MAPK isoform ERK1/2, but not p38, were higher under hypoxic conditions than normoxia, and its activation was further augmented by treatment of cells with transforming growth factor-beta. In hypoxia, transforming growth factor-beta sustained phosphorylated p38 expression for an extended time period. Pharmacological inhibition of ERK1/2 and p38 enzymatic activity resulted in a decrease in Sox-9, aggrecan, and collagen type II mRNA levels. CONCLUSIONS: Our results indicate that hypoxia and transforming growth factor-beta drive mesenchymal stem cell differentiation towards a phenotype consistent with that of the nucleus pulposus. Measurement of selected signaling molecules and response to specific inhibitors suggest involvement of MAPK signaling pathways. It is concluded that mesenchymal stem cells could be used to repopulate the damaged or degenerate intervertebral disc.

Animals↗