The spinal cord injury-induced immune deficiency syndrome: results of the SCIentinel study.

Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections. The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI. The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures. Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters. Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of -0.43 (95% CI: -0.66; -0.20) at 14 days. Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [-0.27 (95% CI: -0.45; -0.10)] and immunoglobulin A [-0.25 (95% CI: -0.49; -0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery. Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI.

Comparison of sagittal vertical axis and decompression on the clinical outcome of cervical spondylotic myelopathy.

OBJECTIVE: Decompression and cervical balance are major goals in the surgical treatment of cervical spondylotic myelopathy (CSM). Cervical balance is assumed to be a key factor for neurological recovery and pain reduction. Surgical reduction of C2-7 sagittal vertical axis (SVA) correlates with clinical improvement. However, it remains unclear, how much or even if correction is necessary for clinical improvement as long as surgery results in successful decompression. We aim to evaluate the role of radiological cervical balance parameter on the short-term course of CSM. METHODS: This is a retrospective study with prospectively collected data of 90 patients. The authors identified 45 patients suffering from CSM that underwent decompressive surgery and instrumentation and showed an increased C2-7 sagittal vertical axis (SVA) after surgery. 45 consecutive patients with a decreased C2-7 SVA were selected as a control group. RESULTS: Surgery improved the clinical outcome of both groups significantly. No differences could be seen comparing neck pain and neurological improvement between both groups. An increased C2-7 SVA did not correlate with an inferior clinical outcome. T1-slope correlated with the Cobb-angle. CONCLUSIONS: Decompression and stabilization appear to be key elements of surgical treatment of CSM. In short terms, clinical improvement does not appear to affect patients negatively who show a larger C2-7 SVA after surgery. Optimal C2-7 SVA and necessity for a specific C2-7 correction is unclear. The term "balance" remains a complex entity without clear definition.

Degeneration of Lumbar Intervertebral Discs: Characterization of Anulus Fibrosus Tissue and Cells of Different Degeneration Grades.

Intervertebral disc (IVD) herniation and degeneration is a major source of back pain. In order to regenerate a herniated and degenerated disc, closure of the anulus fibrosus (AF) is of crucial importance. For molecular characterization of AF, genome-wide Affymetrix HG-U133plus2.0 microarrays of native AF and cultured cells were investigated. To evaluate if cells derived from degenerated AF are able to initiate gene expression of a regenerative pattern of extracellular matrix (ECM) molecules, cultivated cells were stimulated with bone morphogenetic protein 2 (BMP2), transforming growth factor ß1 (TGFß1) or tumor necrosis factor-α (TNFα) for 24 h. Comparative microarray analysis of native AF tissues showed 788 genes with a significantly different gene expression with 213 genes more highly expressed in mild and 575 genes in severe degenerated AF tissue. Mild degenerated native AF tissues showed a higher gene expression of common cartilage ECM genes, whereas severe degenerated AF tissues expressed genes known from degenerative processes, including matrix metalloproteinases (MMP) and bone associated genes. During monolayer cultivation, only 164 differentially expressed genes were found. The cells dedifferentiated and altered their gene expression profile. RTD-PCR analyses of BMP2- and TGFß1-stimulated cells from mild and severe degenerated AF tissue after 24 h showed an increased expression of cartilage associated genes. TNFα stimulation increased MMP1, 3, and 13 expression. Cells derived from mild and severe degenerated tissues could be stimulated to a comparable extent. These results give hope that regeneration of mildly but also strongly degenerated disc tissue is possible.

Proliferation, Migration, and ECM Formation Potential of Human Annulus Fibrosus Cells Is Independent of Degeneration Status.

OBJECTIVE: The objective was to evaluate the proliferating, migratory and extracellular matrix (ECM) forming potential of annulus fibrosus cells derived from early (edAFC) or advanced (adAFC) degenerative tissue and their usability as a possible cell source for regenerative approaches for AF closure. DESIGN: EdAFC (n = 5 Pfirrman score of 2-3) and adAFC (n = 5 Pfirrman score of 4-5) were isolated from tissue of patients undergoing spine stabilizing surgery. Cell migration on stimulation with human serum (HS), platelet-rich plasma (PRP), and transforming growth factor ß-3 (TGFB3) was assessed by migration assay and proliferation was assessed on stimulation with HS. Induction of ECM synthesis was evaluated by gene expression analysis of AF-related genes in three-dimensional scaffold cultures that have been stimulated with 5% PRP or 10 ng/mL TGFB3 and histologically by collagen type I, type II, alcian blue, and safranin-O staining. RESULTS: EdAFC and adAFC were significantly attracted by 10% HS and 5% PRP. Additionally, both cell groups proliferated under stimulation with HS. Stimulation with 10 ng/mL TGFB3 showed significant induction of gene expression of collagen type II and aggrecan, while 5% PRP decreased the expression of collagen type I. Both cell groups showed formation of AF-like ECM after stimulation with TGFB3, whereas stimulation with PRP did not. CONCLUSIONS: Our study demonstrated that AF cells retain their potential for proliferation, migration, and ECM formation independent of the degeneration status of the tissue. Proliferation, migration, and ECM synthesis of the endogenous AF cells can be supported by different supplements. Hence, endogenous AF cells might be a suitable cell source for a regenerative repair approaches.

Chemokine CCL25 Induces Migration and Extracellular Matrix Production of Anulus Fibrosus-Derived Cells.

Intervertebral disc degeneration is a major source of back pain. For intervertebral disc regeneration after herniation a fast closure of anulus fibrosus (AF) defects is crucial. Here, the use of the C-C motif chemokine ligand 25 (CCL)25 in comparison to differentiation factors such as transforming growth factor (TGF)ß3, bone morphogenetic protein (BMP)2, BMP7, BMP12, and BMP14 (all in concentrations of 10, 50 and 100 ng/mL) was tested in an in vitro micro mass pellet model with isolated and cultivated human AF-cells (n = 3) to induce and enhance AF-matrix formation. The pellets were differentiated (serum-free) with supplementation of the factors. After 28 days all used factors induced proteoglycan production (safranin O staining) and collagen type I production (immunohistochemical staining) in at least one of the tested concentrations. Histomorphometric scoring revealed that TGFß3 delivered the strongest induction of proteoglycan production in all three concentrations. Furthermore, it was the only factor able to facilitate collagen type II production, even higher than in native tissue samples. CCL25 was also able to induce proteoglycan and collagen type I production comparable to several BMPs. CCL25 could additionally induce migration of AF-cells in a chemotaxis assay and therefore possibly aid in regeneration processes after disc herniation by recruiting AF-cells.

Empty polyetheretherketone (PEEK) cages in anterior cervical diskectomy and fusion (ACDF) show slow radiographic fusion that reduces clinical improvement: results from the prospective multicenter "PIERCE-PEEK" study.

BACKGROUND: Anterior cervical diskectomy and fusion (ACDF) is a well-established surgical treatment for radiculopathy and myelopathy. Previous studies showed that empty PEEK cages have lower radiographic fusion rates, but the clinical relevance remains unclear. This paper's aim is to provide high-quality evidence on the outcomes of ACDF with empty PEEK cages and on the relevance of radiographic fusion for clinical outcomes. METHODS: This large prospective multicenter clinical trial performed single-level ACDF with empty PEEK cages on patients with cervical radiculopathy or myelopathy. The main clinical outcomes were VAS (0-10) for pain and NDI (0-100) for functioning. Radiographic fusion was evaluated by two investigators for three different aspects. RESULTS: The median (range) improvement of the VAS pain score was: 3 (1-6) at 6 months, 3 (2-8) at 12 months, and 4 (2-8) at 18 months. The median (range) improvement of the NDI score was: 12 (2-34) at 6 months, 18 (4-46) at 12 months, and 22 (2-44) at 18 months. Complete radiographic fusion was reached by 126 patients (43%) at 6 months, 214 patients (73%) at 12 months, and 241 patients (83%) at 18 months. Radiographic fusion was a highly significant (p < 0.001) predictor of the improvement of VAS and NDI scores. CONCLUSION: This study provides strong evidence that ACDF is effective treatment, but the overall rate of radiographic fusion with empty PEEK cages is slow and insufficient. Lack of complete radiographic fusion leads to less improvement of pain and disability. We recommend against using empty uncoated pure PEEK cages in ACDF. TRIAL REGISTRATION: ISRCTN42774128. Retrospectively registered 14 April 2009.

The influence of sagittal profile alteration and final lordosis on the clinical outcome of cervical spondylotic myelopathy. A Delta-Omega-analysis.

PURPOSE: Decompression and maintaining or restoring a cervical lordosis are major goals in the surgical treatment of cervical spondylotic myelopathy (CSM). Numerous studies support the assumption that cervical lordosis is a key factor for neurological recovery and pain reduction. However, even kyphotic patients can be asymptomatic. The balance of the spine is subject of an increasing number of publications. The main purpose of the study was to evaluate the validity of lordotic alignment on the course of CSM and to set this parameter in context with well-validated tools, namely the modified Japanese Orthopaedic Association scoring system (mJOAS) and the visual analogue scale (VAS), to predict and measure the clinical outcome after surgery. METHODS: This is a retrospective study with prospectively collected data of a heterogeneous cohort. The authors analyzed the records of 102 patients suffering from CSM that underwent decompressive surgery and instrumentation. Clinical outcome was assessed by using the mJOAS, VAS and Odom's criteria. The radiological analysis involved comparison of pre- and postoperative radiographs. The patients were divided into subgroups to be able to compare the influence of various amounts of correction (3 Delta-groups: <0°, 1-7° and ≥8°) and final lordosis (4 Omega-groups: 0-7°, 8-14°, 15-21°, ≥22°). RESULTS: 219 levels were fused in 102 patients. Surgery improved the clinical outcome of all groups significantly. A lordotic profile was achieved in all analyzed groups. Patients that showed small lordosis after surgery (<8°) did not have an inferior clinical outcome compared to patients with larger cervical lordosis (>14°). The comparison of Odom's criteria showed that preoperatively kyphotic patients benefitted more from surgery than lordotic patients (p = 0.029), but no differences could be seen comparing neck pain and neurological improvement. The improvement of pain and neurological impairment measured by VAS and mJOAS supports the statistical impact and validity of the data despite comparatively small numbers of patients. The lack of postoperative kyphosis is a major limitation of the study to encompass the impact of sagittal alignment on clinical outcome. CONCLUSIONS: Decompression and stabilization appear to be key elements of surgical treatment of CSM. While the achievement of cervical lordosis remains a major goal of surgery, clinical improvement is not hindered in patients who show small lordosis. However, kyphosis should be eliminated in symptomatic patients. The terms "balance" and "physiologic lordosis" remain complex entities without clear definition. To check the results of our study controlled randomized trials to validate and determine the exact role of cervical balance on the course of CSM would be helpful.

Four-year results of a prospective single-arm study on 200 semi-constrained total cervical disc prostheses: clinical and radiographic outcome.

OBJECTIVE Recent studies have described encouraging outcomes after cervical total disc replacement (cTDR), but there are also critical debates regarding the long-term effects of heterotopic ossification (HO) and the prevalence of adjacent-level degeneration. The aim in this paper was to provide 4-year clinical and radiographic outcome results on the activ C disc prosthesis. METHODS A total of 200 subjects underwent single-level activ C (Aesculap AG) implantation between C-3 and C-7 for the treatment of symptomatic degenerative disc disease. Clinical and radiographic assessments were performed preoperatively, intraoperatively, at discharge, and again at 6 weeks, 6 months, 1 year, 2 years, and 4 years. Radiographic evaluations were done by an independent core laboratory using a specific software for quantitative motion analysis. RESULTS Neck Disability Index (NDI) and visual analog scale (VAS) score for neck and arm pain decreased significantly from baseline to the 4-year follow-up. The mean improvement for NDI was 20, for VAS severity and frequency of neck pain 26.4 and 28, and for VAS severity and frequency of arm pain 30.7 and 35.1, respectively. The neurological situation improved for the majority of patients (86.4%); 76.1% of cases were asymptomatic. Subsequent surgical interventions were reported in 7% of the cases, including device removals in 3%. In 2.5% a subsidence greater than 3 mm was recorded; 1 of these cases also had a migration greater than 3 mm. No device displacement, expulsion, disassembly, loose or fractured device, osteolysis, or facet joint degeneration at the index level was observed. Segmental lordotic alignment changed from -2.4° preoperatively to -6.2° at 4 years, and postoperative height was maintained during the follow-up. Advanced HO (Grade III and IV) was present in 27.1% of the cases; 82.4% showed segmental mobility. A progression of radiographic adjacent-segment degeneration occurred in 28.2%, but only 4.5% required surgical treatment. CONCLUSIONS The activ C is a safe and effective device for cervical disc replacement confirming the encouraging results after cTDR. Clinical trial registration no.: NCT02492724 ( clinicaltrials.gov ).

Transient sacroiliac joint-related pain is a common problem following lumbar decompressive surgery without instrumentation.

OBJECTIVE: Patients with lumbar stenosis profit substantially from decompressive surgery. The change of body position and walking behaviour after successful surgery might lead to changed force effects on the entire spine and on the sacroiliac joint (SIJ). We analyzed the incidence of postoperative SIJ-related pain. METHODS: The authors analyzed the records of 100 consecutive patients from three institutions, who underwent decompressive surgery without instrumentation. The diagnosis of SIJ-related pain was confirmed by periarticular infiltration. The radiological changes of the sacroiliac joint were assessed in plain radiographs in both groups: patients with SIJ pain (group 1) and patients without SIJ pain (group 2) after surgery. RESULTS: 22 patients required medical attention due to SIJ-related pain after surgery. While the walking distance increased substantially in both groups without difference (p=0.150), the analysis of overall satisfaction favoured group 2 (p=0.047). Female patients suffered more from SIJ pain after surgery (p=0.036). Age, severity of radiological changes or number of operated segments appeared not to trigger SIJ-related pain. CONCLUSION: The adaptation of a changed body posture and gait could lead to transient overload of the SIJ and surrounding myofascial structures. The patients should be informed about this possible condition to avoid uncertainty, discontent, unnecessary diagnostics and to induce a quick, specific treatment. Non-diagnosed sacroiliac joint-related pain could be a possible, but reversible reason for the diagnosis of a "failed-back-surgery".

Application of titanium and polyetheretherketone cages in the treatment of pyogenic spondylodiscitis.

OBJECTIVE: Surgical treatment of a pyogenic spondylodiscitis (PSD) involves a fixation and debridement of the affected segment combined with a specific antibiotic therapy. To achieve a proper stability and to avoid pseudarthrosis and kyphotic malposition many surgeons favour the interposition of an anterior graft. Besides autologous bone grafts titanium (TTN) cages have gained acceptance in the treatment of PSD. Polyetheretherketone (PEEK) cages have a more favourable modulus of elasticity than TTN. We compared both cage types. Primary endpoints were the rate of reinfection and radiological results. METHODS: From 2004 to 2013 51 patients underwent surgery for PSD with fixation and TTN or PEEK cage-implantation. While lumbar patients underwent a partial discectomy by the posterior approach, discs of the cervical and thoracic patients had been totally removed from anterior. Clinical and radiological parameters were assessed in 37 eligible patients after a mean of 20.4 months. 21 patients received a PEEK- and 16 patients a TTN-cage. RESULTS: A reinfection after surgery and 3 months of antibiotic therapy was not observed. Solid arthrodesis was found in 90.5% of the PEEK-group and 100% of the TTN-group. A segmental correction could be achieved in both groups. Nonetheless, a cage subsidence was observed in 70.3% of all cases. Comparison of radiological results revealed no differences between both groups. CONCLUSIONS: A debridement and fixation with anterior column support in combination with an antibiotic therapy appear to be the key points for successful treatment of PSD. The application of TTN- or PEEK-cages does not appear to influence the radiological outcome or risk of reinfection, neither does the extent of disc removal in this clinical subset.

The value of intraoperative neurophysiological monitoring for microsurgical removal of conus medullaris lipomas: a 12-year retrospective cohort study.

BACKGROUND: Lipomas in the lower spinal canal can lead to progressive neurological deficits, so they may have to be surgically removed. Intraoperative neurophysiological monitoring serves to minimize the morbidity of the surgical procedure. However, so far there are no evidence-based recommendations which type of monitoring procedure or combination of procedures to choose. METHODS: The aim of this study was to evaluate the feasibility and value of various intraoperative monitoring techniques: motor and sensory evoked potentials (MEP, SEP), free-running and triggered electromyography (EMG). Thirty cases of spinal lipomas of the Conus medullaris (dorsal Type A: 20.0%; caudal Type B: 33.3%; transitional Type C: 46.7%) were retrospectively evaluated over a 12-year period. RESULTS: The patients were mostly pediatric and suffered from persistent pain (73.3%), pareses (56.7%), sensory deficits (43.4%), and/or urogenital dysfunctions (60.0%). SEPs were successfully evoked in 66.7% of cases, MEPs in 86.7% of cases, and EMGs in 100%. MEP alterations correlated with direct mechanical maneuvers in the operating site. SEP changes correlated mostly with physiological events, such as rinsing/cooling of the operating site. Spike-, burst- or tonic train-activity was found in the free-running EMG that occurred only with certain manipulation patterns. Irreversible MEP changes and signal loss in the triggered EMG correlated with post-operative deficits. CONCLUSIONS: The results of this study showed, that intraoperative monitoring could be considered a helpful tool during lipoma tumor surgery near the Conus medullaris. Most reliable results were obtained from transcranial MEPs, free-running EMGs, and triggered EMGs. That's why the authors favor a routine set-up consisting of at least these three techniques, as this enables mapping at the beginning of the operation, continuous functional testing during surgery, and prognosis of the post-operative symptomology.

The SCIentinel study--prospective multicenter study to define the spinal cord injury-induced immune depression syndrome (SCI-IDS)--study protocol and interim feasibility data.

BACKGROUND: Infections are the leading cause of death in the acute phase following spinal cord injury and qualify as independent risk factor for poor neurological outcome ("disease modifying factor"). The enhanced susceptibility for infections is not stringently explained by the increased risk of aspiration in tetraplegic patients, neurogenic bladder dysfunction, or by high-dose methylprednisolone treatment. Experimental and clinical pilot data suggest that spinal cord injury disrupts the balanced interplay between the central nervous system and the immune system. The primary hypothesis is that the Spinal Cord Injury-induced Immune Depression Syndrome (SCI-IDS) is 'neurogenic' including deactivation of adaptive and innate immunity with decreased HLA-DR expression on monocytes as a key surrogate parameter. Secondary hypotheses are that the Immune Depression Syndrome is i) injury level- and ii) severity-dependent, iii) triggers transient lymphopenia, and iv) causes qualitative functional leukocyte deficits, which may endure the post-acute phase after spinal cord injury. METHODS/DESIGN: SCIentinel is a prospective, international, multicenter study aiming to recruit about 118 patients with acute spinal cord injury or control patients with acute vertebral fracture without neurological deficits scheduled for spinal surgery. The assessment points are: i) <31 hours, ii) 31-55 hours, iii) 7 days, iv) 14 days, and v) 10 weeks post-trauma. Assessment includes infections, concomitant injury, medication and neurological classification using American Spinal Injury Association impairment scale (AIS) and neurological level. Laboratory analyses comprise haematological profiling, immunophenotyping, including HLA-DR expression on monocytes, cytokines and gene expression of immune modulators. We provide an administrative interim analysis of the recruitment schedule of the trial. DISCUSSION: The objectives are to characterize the dysfunction of the innate and adaptive immune system after spinal cord injury and to explore its proposed 'neurogenic' origin by analyzing its correlation with lesion height and severity. The trial protocol considers difficulties of enrolment in an acute setting, and loss to follow up. The administrative interim analysis confirmed the feasibility of the protocol. Better understanding of the SCI-IDS is crucial to reduce co-morbidities and thereby to attenuate the impact of disease modifying factors to protect neurological "outcome at risk". This putatively results in improved spinal cord injury medical care. TRIAL REGISTRATION DRKS-ID: DRKS00000122 (German Clinical Trials Registry).

Single- and multi-level anterior decompression and fusion for cervical spondylotic myelopathy--a long term follow-up with a minimum of 5 years.

OBJECTIVE: Cervical spondylotic myelopathy (CSM) is a common disease leading to significant neurological disability. We compared patients suffering from a single- and a multi-level pathology to analyze the influence of the natural course of the disease on the long-term outcome after surgery. METHODS: We analyzed the records of 52 patients with CSM after surgery. The neurological status of the patients was assessed by the modified Japanese Orthopaedic Association Scale (mJOAS). X-rays were conducted before and after surgery. RESULTS: 52 patients were treated by a single-level (n=27) or a multi-level approach (n=25) more than 5 years ago. A significant improvement of the neurological status could be seen even 5 years or more after surgery in both groups without differences. After one year no further improvement could be observed. In the single-level group a trend to a subsequent loss of lordotic correction could be seen. Anterior plates were only used in the multi-level group. CONCLUSION: The anterior approach is an effective procedure to improve the symptoms of a CSM for many years. The risk of a multi-level pathology does not appear to exceed the risks of a single-level pathology concerning clinical long-term outcome after surgery. The clinical success is not hindered by a loss of correction in this specific setting.

Intraoperative neurophysiological monitoring of extracranial-intracranial bypass procedures.

OBJECT: Intraoperative neurophysiological monitoring (IONM) represents an established tool in neurosurgery to increase patient safety. Its application, however, is controversial. Its use has been described as helpful in avoiding neurological deterioration during intracranial aneurysm surgery. Its impact on extracranial-intracranial (EC-IC) bypass surgery involving parent artery occlusion for the treatment of complex aneurysms has not yet been studied. The authors therefore sought to evaluate the effects of IONM on patient safety, the surgeon's intraoperative strategies, and functional outcome of patients after cerebral bypass surgery. Intraoperative neurophysiological monitoring results were compared with those of intraoperative blood flow monitoring to assess bypass graft perfusion. METHODS: Compound motor action potentials (CMAPs) were generated using transcranial electrical stimulation in patients undergoing EC-IC bypass surgery. Preoperative and postoperative motor function was analyzed. To assess graft function, intraoperative flowmetry and indocyanine green fluorescence angiography were performed. Special care was taken to compare the relevance of electrophysiological and blood flow monitoring in the detection of critical intraoperative ischemic episodes. RESULTS: The study included 31 patients with 31 aneurysms and 1 bilateral occlusion of the internal carotid arteries, undergoing 32 EC-IC bypass surgeries in which radial artery or saphenous vein grafts were used. In 11 cases, 15 CMAP events were observed, helping the surgeon to determine the source of deterioration and to react to it: 14 were reversible and only 1 showed no recovery. In all cases, blood flow monitoring showed good perfusion of the bypass grafts. There were no false-negative results in this series. New postoperative motor deficits were transient in 1 case, permanent in 1 case, and not present in all other cases. CONCLUSIONS: Intraoperative neurophysiological monitoring is a helpful tool for continuous functional monitoring of patients undergoing large-caliber vessel EC-IC bypass surgery. The authors' results suggest that continuous neurophysiological monitoring during EC-IC bypass surgery has relevant advantages over flow-oriented monitoring techniques such as intraoperative flowmetry or indocyanine green-based angiography.

Towards biological anulus repair: TGF-ß3, FGF-2 and human serum support matrix formation by human anulus fibrosus cells.

Closure and biological repair of anulus fibrosus (AF) defects in intervertebral disc diseases is a therapeutic challenge. The aim of our study was to evaluate the anabolic properties of bioactive factors on cartilaginous matrix formation by AF cells. Human AF cells were harvested from degenerated lumbar AF tissue and expanded in monolayer culture. AF cell differentiation and matrix formation was initiated by forming pellet cultures and stimulation with hyaluronic acid (HA), human serum (HS), fibroblast growth factor-2 (FGF-2), transforming growth factor-ß3 (TGF-ß3) and TGF-ß3/FGF-2 for up to 4 weeks. Matrix formation was assessed histologically by staining of proteoglycan, type I and type II collagens and by gene expression analysis of typical extracellular matrix molecules and of catabolic matrix metalloproteinases MMP-2 and MMP-13. AF cells, stimulated with HS, FGF-2 and most pronounced with TGF-ß3 or TGF-ß3/FGF-2 formed a cartilaginous matrix with significantly enhanced expression of matrix molecules and of MMP-13. Stimulation of AF cells with TGF-ß3 was accompanied by induction of type X collagen, known to occur in hypertrophic cartilage cells having mineralizing potential. HA did not show any chondro-inductive characteristics. These findings suggest human serum, FGF-2 and TGF-ß3 as possible candidates to support biological treatment strategies of AF defects.

Anterior cervical discectomy and fusion: comparison of titanium and polyetheretherketone cages.

BACKGROUND: Titanium (TTN) cages have a higher modulus of elasticity when compared with polyetheretherketone (PEEK) cages. This suggests that TTN-cages could show more frequent cage subsidence after anterior cervical discectomy and fusion (ACDF) and therefore might lead to a higher loss of correction. We compared the long term results of stand-alone PEEK- and TTN-cages in a comparable patient collective that was operated under identical operative settings. METHODS: From 2002 to 2007 154 patients underwent single-level ACDF for degenerative disc disease (DDD). Clinical and radiological outcome were assessed in 86 eligible patients after a mean of 28.4 months. 44 patients received a TTN- and 42 patients a PEEK-cage. RESULTS: Solid arthrodesis was found in 93.2% of the TTN-group and 88.1% of the PEEK-group. Cage subsidence was observed in 20.5% of the TTN- and 14.3% of the PEEK-group. A significant segmental lordotic correction was achieved by both cage-types. Even though a loss of correction was found at the last follow-up in both groups, it did not reach the level of statistical significance. Statistical analysis of these results revealed no differences between the TTN- and PEEK-group.When assessed with the neck disability index (NDI), the visual analogue scale (VAS) of neck and arm pain and Odom's criteria the clinical data showed no significant differences between the groups. CONCLUSIONS: Clinical and radiological outcomes of ACDF with TTN- or PEEK-cages do not appear to be influenced by the chosen synthetic graft. The modulus of elasticity represents only one of many physical properties of a cage. Design, shape, size, surface architecture of a cage as well as bone density, endplate preparation and applied distraction during surgery need to be considered as further important factors.

A 3D environment for anulus fibrosus regeneration.

OBJECT: Biological repair strategies for the treatment of degenerated intervertebral discs are of growing interest. In addition to the development of nucleus pulposus implants to restore disc height and relieve pain, there is growing demand for an appropriate method for reconstructing the anulus fibrosus (AF). The aim of this pilot study was to evaluate the applicability of a resorbable 3D polymer of pure polyglycolic acid (PGA) combined with hyaluronan for the use in cell-free and cell-based regeneration and repair of the AF. METHODS: Adult human AF cells were expanded in vitro using human serum and rearranged three dimensionally in hyaluronan-PGA scaffolds that were stabilized with fibrin for in vitro analyses. The capacity of dedifferentiated AF cells to redifferentiate was evaluated after 2 weeks of culture, using propidium iodide/fluorescein diacetate staining, gene expression analysis of typical marker genes, and histological staining of proteoglycans. RESULTS: The propidium iodide/fluorescein diacetate staining demonstrated that vital human AF cells were evenly distributed within the construct. The induction of typical AF marker genes such as collagen Types I-III indicated the initiation of AF redifferentiation by 3D assembly in hyaluronan-PGA. Histological analysis of the constructs showed initial formation of an AF-like matrix comprising proteoglycans. CONCLUSIONS: The results suggest that the 3D arrangement of human AF cells in resorbable hyaluronan-PGA scaffolds cultured in the presence of human serum is an excellent system for AF cell redifferentiation.

Delayed formation of a devastating granulomatous process after metal-on-metal lumbar disc arthroplasty.

STUDY DESIGN: A case report. OBJECTIVE: We report the case of a female patient with a delayed and devastating complication after lumbar total disc arthroplasty (TDA). SUMMARY OF BACKGROUND DATA: The formation of granulomatous tissue surrounding arthroplasty devices has been described after hip replacements, but has been reported only in a few cases after spinal surgery. METHODS: Retrospective case study of a female patient with a delayed complication after lumbar TDA with a metal-on-metal device for degenerative disc disease at level L4-L5 and with follow-up examination 8 months after surgery. RESULTS: About 11 months after lumbar arthroplasty surgery, the patient developed back pain and progressive weakness of both legs. A computed tomographic scan revealed soft tissue surrounding the TDA device and infiltrating the spinal canal. The revision surgery (posterior fixation and decompression) did not improve the clinical situation. The progressive growth of soft tissue led to a high-grade paraparesis and occlusion of the left ureter as well as of both common iliac veins and the infrarenal part of the vena cava inferior. The TDA device was removed. Another posterior surgery with extensive instrumentation was necessary to treat the destruction of vertebral bodies L4 and L5 2 months after the last surgery. The histopathological analysis revealed a granulomatous necrotizing inflammation. After the last revision surgery, the patient's back pain decreased. At her last follow-up, no further growth of the soft tissue mass could be found. CONCLUSION: Metal-on-Metal TDA devices can induce a tumor-like growth with devastating consequences. The reduction of device motion by posterior stabilizing surgery does not seem to stop the growth of the granulomatous mass. The device has to be removed.

The analysis of segmental mobility with different lumbar radiographs in symptomatic patients with a spondylolisthesis.

PURPOSE: Lumbar flexion-extension radiographs in standing position (SFE) are the most commonly used imaging method to evaluate segmental mobility. Many surgeons use SFE to disclose abnormal vertebral motion and base their decision for surgical fusion on its results. We tested the hypothesis that imaging in standing and recumbent position (SRP) reveals a higher sagittal translation (ST) and sagittal rotation (SR) in symptomatic patients than with SFE. MATERIALS AND METHODS: We analysed images of 100 symptomatic patients with a low-grade spondylolisthesis that underwent surgical fusion. To determine the ST and SR in SRP, we compared the images taken in the recumbent position in the CT with images taken in the standing position during the routine plain radiography. RESULTS: The measurement of ST revealed an absolute value of 2.3 ± 1.5 mm in SFE and 4.0 ± 2.0 mm in SRP and differed significantly (p = 0.001). The analysis of the relative value showed an ST of 5.9 ± 3.9% in SFE and 7.8 ± 5.4% in SRP (p = 0.008). The assessment of ST in flexion and in a recumbent position (FRP) revealed the highest ST (4.6 ± 2.5 mm or 9.2 ± 5.7%). Comparison of SR showed the highest rotation in SFE (6.1° ± 3.8°), however, compared to SRP (5.4° ± 3.3°), it missed the level of significance (p = 0.051). CONCLUSIONS: For evaluation of ST in symptomatic patients with spondylolisthesis SRP appears to be more suitable than SFE, while a pathological SR is better revealed in SFE. The analysis of SRP might offer a complementary method to detect or exclude pathological mobility in more cases.

Polymethylmethacrylate-assisted ventral discectomy: rate of pseudarthrosis and clinical outcome with a minimum follow-up of 5 years.

BACKGROUND: Polymethylmethacrylate (PMMA) assisted ventral discectomy has been criticized for high rates of graft migration and pseudarthrosis when compared with various other fusion procedures for the treatment of cervical degenerative disc disease (DDD), therefore rendering it not the preferred choice of treatment today. Recently however spine surgery has been developing towards preservation rather than restriction of motion, indicating that fusion might not be necessary for clinical success. This study presents a long term comparison of clinical and radiological data from patients with pseudarthrosis and solid arthrodesis after PMMA assisted ventral discectomy was performed. METHODS: From 1986 to 2004 416 patients underwent ventral discectomy and PMMA interposition for DDD. The clinical and radiological outcome was assessed for 50 of 127 eligible patients after a mean of 8.1 years. Based on postoperative radiographs the patients were dichotomized in those with a pseudarthrosis (group A) and those with solid arthrodesis (group B). RESULTS: Pseudarthrosis with movement of more than 2 of the operated segment was noted in 17 cases (group A). In 33 cases no movement of the vertebral segment could be detected (group B). The analysis of the clinical data assessed through the neck disability index (NDI), the visual analogue scale (VAS) of neck and arm pain and Odom's criteria did not show any significant differences between the groups.Patients from group B showed a trend to higher adjacent segment degeneration (ASD) than group A (p = 0.06). This correlated with the age of the patients. CONCLUSIONS: PMMA assisted discectomy shows a high rate of pseudarthrosis. But the clinical long-term success does not seem to be negatively affected by this.