Nicola Specchia

Cytokines and growth factors in the protruded intervertebral disc of the lumbar spine

Abstract. Nerve root irritation induced by factors produced by the intervertebral disc may play a crucial role in the pathophysiology of sciatic pain production. In this study we used immunohistochemistry to investigate the presence of transforming growth factor-β1 (TGF-β1), insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6), IL-6-receptor (IL-6R) and fibronectin in lumbar disc bioptic specimens from 30 patients with disc herniation (protrusion type). Chondrocytes of herniated discs stained positive for TGF-β1, IGF-1, IL-6 and fibronectin. We demonstrated for the first time the presence of IL-6-R in the chondrocytes of herniated tissue. Specimens from autoptic healthy tissue were used as controls. In these sections no immunoreaction for TGF-β1, IL-6, or IL-6R was found, while they expressed IGF-1 and fibronectin, but in lower quantities than herniated discs. These results demonstrated the production of factors such as TGF-β1, IGF-1, IL-6, IL-6R and fibronectin at the site of lumbar disc herniation.

Novel concepts in the evaluation and treatment of high-dysplastic spondylolisthesis

The classification system of spondylolisthesis proposed by Marchetti and Bartolozzi is the most practical regarding prognosis and treatment and includes the description of both low- and high-dysplastic developmental spondylolisthesis (HDDS). Unfortunately, it does not provide strict criteria on how to differentiate between these two subtypes. The accepted treatment for HDDS is surgical. However, there is no consensus on how to surgically stabilize this subtype of spondylolisthesis, and although the concept of reducing spinal deformity before fusion is attractive, the issue of surgical reduction versus in situ fusion remains controversial, especially for HDDS (Meyerding Grades III and IV). The purpose of this study was (1) to describe the severity index (SI) as a simple method that can be used in the identification of low-dysplastic developmental spondylolisthesis from HDDS allowing earlier surgical stabilization to prevent slip progression, (2) to provide guidelines for using the unstable zone for the inclusion of L4 in stabilization, and (3) to describe a surgical technique in the reduction and stabilization of this challenging surgical entity in an attempt to decrease the risk of iatrogenic L5 neurologic injury. The concepts of SI and unstable zone in the evaluation and treatment of HDDS are relatively new. In our study, patients with an SI value >20% were classified as having HDDS and surgical stabilization was offered. In addition, all vertebrae that were contained in the defined unstable zone were surgically instrumented and fused with attempts at anatomic reduction. This case series involved the retrospective radiological review of 25 consecutive patients surgically treated for HDDS between April 2000 and September 2004 by two senior surgeons. All 25 patients had a minimum 3-year follow-up. Reduction of slip, lumbosacral kyphosis, sacral inclination, fusion rate, maintenance of reduction, and iatrogenic L5 neurologic injury were evaluated. Twenty-two patients underwent a single-level L5–S1 fusion. Three patients had extension of the L5–S1 fusion to include L4 because it fell into the unstable zone. Slip improved from 67.2 to 13.6%, focal L5–S1 kyphosis improved from +17.5° to −6.4°. There were no pseudoarthroses and all patients had radiographic evidence of solid bony fusion at latest follow-up. To date, there have been no re-operations secondary to progression of deformity or loss of fixation. Two re-operations were performed, one for a superficial wound infection, the other for further laparoscopic decompression for continued L5 nerve root symptoms after the index surgery. One patient developed an iatrogenic L5 radiculopathy with dysaesthesiae 3 days postoperatively which completely resolved over 6 weeks. HDDS is best treated surgically. Early identification and stabilization of this challenging surgical entity could prevent the progression of slip and deformity making the index surgery less technically demanding. Vertebrae that are contained in the unstable zone can be instrumented and stabilized so that progression of the deformity and re-operation might be avoided. The authors suggested surgical technique can provide a way to restore sagittal balance, provide an environment for successful fusion, and decrease the risk of iatrogenic L5 neurologic injury.

A Prospective, Randomized, Controlled, Multicenter Study of Osteogenic Protein-1 in Instrumented Posterolateral Fusions Report on Safety and Feasibility

Study Design. A prospective, randomized, controlled, multicenter clinical study. Objective. To evaluate the safety and feasibility of osteogenic protein (OP)-1 in 1-level lumbar spine instrumented posterolateral fusions. Summary of Background Data. Instrumented posterolateral fusion with the use of autograft is a commonly performed procedure for a variety of spinal disorders. However, harvesting of bone from the iliac crest is associated with complications. A promising alternative for autograft are bone morphogenetic proteins. Methods. As part of a larger prospective, randomized, multicenter study, 36 patients were included, who received a 1-level instrumented posterolateral fusion of the lumbar spine. All patients had a degenerative or isthmic spondylolisthesis with symptoms of neurologic compression. There were 2 treatment arms: OP-1 combined with locally available bone from laminectomy (OP-1 group) or iliac crest autograft (autograft group). The primary outcome was the fusion rate based on a computed tomography scan after 1-year follow-up. The clinical outcome was measured using the Oswestry Disability Index. Additionally, the safety of OP-1 was evaluated by comparing the number and severity of adverse events that occurred between both groups. Results. Using strict criteria, fusion rates of 63% were found in the OP-1 group and 67% in the control group (P = 0.95). There was a decrease in Oswestry scores at subsequent postoperative time points compared with preoperative values (P > 0.001). There were no significant differences in the mean Oswestry scores between the study group and control group at any time point (P = 0.56). No product-related adverse events occurred. Conclusion. The results demonstrate that OP-1 combined with locally obtained autograft is a safe and effective alternative for iliac crest autograft in instrumented single-level posterolateral fusions of the lumbar spine. The main advantage of OP-1 is that it avoids morbidity associated with the harvesting of autogenous bone grafts from the iliac crest.

Endoscopic transnasal odontoid resection to decompress the bulbo-medullary junction: a reliable anterior minimally invasive technique without posterior fusion

PurposeAnterior decompression of the craniovertebral junction is reserved to patients with irreducible ventral bulbo-medullary lesions and rapidly deteriorating neurological functions. Classically performed through the transoral approach, the exposure of this region can be now achieved by a minimally invasive endonasal endoscopic approach (EEA).MethodsFour patients with irreducible, anterior bulbo-medullary compression due to rheumatoid pannus and basilar invagination were enrolled. The imaged-guided EEA was used to resect the odontoid process, trying to preserve the C1 anterior arch.ResultsNeurological improvement and adequate bulbo-medullary decompression were obtained in all patients. In two cases, anterior C1 ring was preserved. These patients did not required a posterior fusion.ConclusionsCompared with the standard transoral technique, the EEA provides the same good exposure but with potentially less complications. The preservation of the anterior C1 arch can contribute to avoid cranial settling and posterior fusion with its related risk of subaxial instability.

Endoscopic endonasal odontoidectomy with anterior C1 arch preservation in elderly patients affected by rheumatoid arthritis

BACKGROUND CONTEXT Rheumatoid arthritis is the most common inflammatory disease involving the spine with predilection for the craniovertebral segment. Surgery is usually reserved to patients with symptomatic craniovertebral junction (CVJ) instability, basilar invagination, or upper spinal cord compression by rheumatoid pannus. Anterior approaches are indicated in cases of irreducible ventral bulbo-medullary compression. Classically performed through the transoral approach, the exposure of this region can be now achieved by a minimally invasive endonasal endoscopic approach (EEA). PURPOSE The aim of this article is to demonstrate the feasibility of performing an odontoidectomy and a rheumatoid pannus removal by a minimally invasive EEA, preserving the anterior C1 arch continuity and avoiding a posterior fixation procedure. STUDY DESIGN Technical description and cohort report. METHODS We report three cases of elderly patients with a long history of rheumatoid arthritis and irreducible anterior bulbo-medullary compression secondary to basilar invagination and/or rheumatoid pannus. Anterior decompression was achieved by an endonasal image-guided fully endoscopic approach. RESULTS Neurological improvement and adequate bulbo-medullary decompression were obtained in all cases. The anterior C1 arch continuity was preserved, and none of the patients required a subsequent posterior fixation. CONCLUSIONS Anterior decompression by a minimally invasive EEA could represent an innovative option for the treatment of irreducible ventral CVJ lesions in elderly patients with rheumatoid arthritis. This approach permits the preservation of the anterior C1 arch and the avoidance of a posterior fixation, thus preserving the rotational movement at C0-C2 segment and reducing the risk of a subaxial instability development.

Responsiveness of Dupuytren’s disease fibroblasts to 5α-dihydrotestosterone

Abstract Purpose We recently showed that androgen receptors are expressed in Dupuytrens contracture. The aim of the present work was to test the responsiveness of Dupuytrens fibroblasts to 5α-dihydrotestosterone (5α-DHT), the active form of testosterone. Methods Cultured palmar fascia cells from 10 patients with Dupuytrens contracture and 4 normal subjects were exposed to 5α-DHT (10 or 100 ng/mL) for 1, 3, 7, and 15 days. Their phenotype was analyzed immunohistochemically for α-smooth muscle actin and androgen receptor expression and proliferation rates were studied. Results At 15 days the higher concentration of 5α-DHT induced an increase in Dupuytrens fibroblast proliferation, whereas anti-α-smooth muscle actin exhibited the strongest expression. At the same time point androgen receptor expression decreased with the lower concentration and disappeared altogether with the higher dose of 5α-DHT. Conclusions The palmar fascia is a target tissue for androgen action via androgen receptors. Further studies are required to determine whether control of androgen receptor may control the evolution of Dupuytrens disease.

OP-1 compared with iliac crest autograft in instrumented posterolateral fusion a randomized, multicenter non-inferiority trial

BACKGROUND Spinal fusion with the use of autograft is a commonly performed procedure. However, harvesting of bone from the iliac crest is associated with complications. Bone morphogenetic proteins (BMPs) are extensively used as alternatives, often without sufficient evidence of safety and efficacy. The purpose of this study was to investigate non-inferiority of osteogenic protein-1 (OP-1, also known as BMP-7) in comparison with iliac crest bone graft in posterolateral fusions. METHODS This study was a randomized, controlled multicenter trial. Patients who underwent a single-level instrumented posterolateral fusion of the lumbar spine for degenerative or isthmic spondylolisthesis with symptoms of neurological compression were randomized to receive OP-1 combined with local bone (OP-1 group) or autologous bone graft from the iliac crest combined with local bone (autograft group). The primary outcome was overall success, defined as a combination of clinical success and evidence of fusion on computed tomography (CT) scans, at one year postoperatively. RESULTS One hundred and nineteen patients were included in the study, and analysis of the overall outcome was performed for 113. Non-inferiority of OP-1 compared with iliac crest autograft was not found at one year, with a success rate of 40% in the OP-1 group versus 54% in the autograft group (risk difference = -13.3%, 90% confidence interval [CI] = -28.6% to +2.10%). This was due to the lower rate of fusion (the primary aim of OP-1 application) seen on the CT scans in the OP-1 group (54% versus 74% in the autograft group, p = 0.03). There were no adverse events that could be directly related to the use of OP-1. CONCLUSIONS OP-1 with a collagen carrier was not as effective as autologous iliac crest bone for achieving fusion and cannot be recommended in instrumented posterolateral lumbar fusion procedures. LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Endoscopic Transnasal Odontoidectomy With Anterior C1 Arch Preservation and Anterior Vertebral Column Reconstruction in Patients With Irreducible Bulbomedullary Compression by Complex Craniovertebral Junction Abnormalities: Operative Nuance

BACKGROUND: During the past decades, the transoral transpharyngeal approach has been advocated as the standard route for the removal of odontoid causing an irreducible symptomatic neural compression. However, it may be potentially associated with a significant built-in morbidity because of the splitting of the soft palate for an adequate working angle, tracheostomy, and incision of the oral mucosa, causing exposure to a higher risk of infection by oral flora. OBJECTIVE: To describe our experience with the minimally invasive pure endoscopic transnasal odontoidectomy in patients with bulbomedullary compression affected by complex anterior craniovertebral junction abnormalities. METHODS: Five patients underwent a pure endoscopic neuronavigation-assisted transnasal odontoidectomy with anterior C1 arch preservation. Moreover, the anterior cervical spine column was reconstructed by filling the gap between the C1 arch and the residual C2 body with autologous/artificial bone. Neither tracheostomy nor enteral tube feeding were needed in any case. RESULTS: A postoperative neurological improvement was observed in all patients. Postoperative imaging confirmed a satisfactory spinal cord decompression with cervical anterior column arthrodesis, and without evidence of instability at follow-up, so far. CONCLUSION: The endoscopic transnasal approach seems to represent an efficient and safe alternative to the transoral route for the resection of odontoid process causing irreducible bulbomedullary compression. It provides a straightforward and minimally invasive natural surgical corridor to the anterior craniocervical junction, allowing a better working angle with preservation of spine biomechanics, while minimizing potential comorbidities.

Is posterior fixation alone effective to prevent the late kyphosis after T-L fracture?

IntroductionThe posterior transpedicular fixation technique is a standard procedure for stabilizing the injured thoracolumbar spine but the long-term results of this approach are controversial. Clear guidelines are missing and the literature shows complete disagreement regarding indications, approaches, surgical techniques, and type of fixation.Material and methodThe objective of this study is to investigate if the surgical treatment by posterior approach alone is always enough to prevent the late kyphotic deformity through the retrospective analysis of 219 patients affected with a thoracolumbar injury. Follow-up examinations included radiographic measurements of the sagittal index (SI) and the sagittal plane kyphosis (SPK).ResultResults show that, at the follow-up, the SI remains almost stable after the surgical correction, while the SPK (which describes the eventual injury of the affected intervertebral disc) decreases indicating a progressive regional kyphotic deformity. Thus, in some cases posterior fixation alone is not sufficient for long-term spinal stabilization and often can be not effective to prevent the late kyphotic deformity.

Endoscopic Endonasal Odontoidectomy with Anterior C1 Arch Preservation in Rheumatoid Arthritis: Long-Term Follow-Up and Further Technical Improvement by Anterior Endoscopic C1-C2 Screw Fixation and Fusion

OBJECTIVE To examine the long-term outcomes (minimum of 4.5 years) of endoscopic endonasal odontoidectomy (EEO) with preservation of anterior C1 ring to treat irreducible ventral bulbo-medullary compressions in rheumatoid arthritis (RA) and to illustrate a novel technique of anterior pure endoscopic craniovertebral junction (CVJ) reconstruction and fusion. In fact, long-term clinical studies are still lacking to elucidate the effective role of EEO and whether it can obviate the need for posterior fixation. METHODS From November 2008 to January 2012, clinical and radiologic data of 7 patients presenting with RA and associated irreducible bulbo-medullary compression treated with EEO were analyzed retrospectively. In all patients, decompression was achieved by EEO with anterior C1 arch preservation. In the last 2 patients, after EEO, we used the spared anterior C1 arch for reconstruction of anterior column of CVJ by positioning, under pure endoscopic guidance, autologous bone and 2 tricortical screws between the anterior arch of C1 and the residual odontoid. All patients were examined clinically with Ranawat classification and radiographically with computed tomography, magnetic resonance imaging, and dynamic radiography immediately after surgery and during follow-up. RESULTS Adequate bulbo-medullary decompression with anterior C1 arch preservation was obtained in all cases. At follow-up (average, 66.2 months; range, 51-91 months) all patients experienced an improvement at least of one Ranawat classification level and presented no clinical or radiologic signs of instability. CONCLUSIONS EEO with anterior C1 arch sparing provides satisfying long-term results for irreducible ventral CVJ lesions in RA. The preservation of anterior C1 arch and, when possible, the reconstruction of anterior CVJ can prevent the need for posterior fusion.