Expression and activity of hyaluronidases HYAL-1, HYAL-2 and HYAL-3 in the human intervertebral disc.

PURPOSE: Hyaluronic acid plays an essential role in water retention of the intervertebral disc (IVD) and thus provides flexibility and shock absorbance in the spine. Hyaluronic acid gets degraded by hyaluronidases (HYALs), and some of the resulting fragments were previously shown to induce an inflammatory and catabolic response in human IVD cells. However, no data currently exist on the expression and activity of HYALs in IVD health and disease. METHODS: Gene expression, protein expression and activity of HYALs were determined in human IVD biopsies with different degrees of degeneration (n = 50 total). Furthermore, freshly isolated human IVD cells (n = 23 total) were stimulated with IL-1ß, TNF-α or H2O2, followed by analysis of HYAL-1, HYAL-2 and HYAL-3 gene expression. RESULTS: Gene expression of HYAL-1 and protein expression of HYAL-2 significantly increased in moderate/severe disc samples when compared to samples with no or low IVD degeneration. HYAL activity was not significantly increased due to high donor-donor variation, but seemed overall higher in the moderate/severe group. An inflammatory environment, as seen during IVD disease, did not affect HYAL-1, HYAL-2 or HYAL-3 expression, whereas exposure to oxidative stress (100 µM H2O2) upregulated HYAL-2 expression relative to untreated controls. CONCLUSION: Although HYAL-1, HYAL-2 and HYAL-3 are all expressed in the IVD, HYAL-2 seems to have the highest pathophysiological relevance. Nonetheless, further studies will be needed to comprehensively elucidate its significance and to determine its potential as a therapeutic target. These slides can be retrieved under Electronic Supplementary Material.

TRPC6 in simulated microgravity of intervertebral disc cells.

PURPOSE: Prolonged bed rest and microgravity in space cause intervertebral disc (IVD) degeneration. However, the underlying molecular mechanisms are not completely understood. Transient receptor potential canonical (TRPC) channels are implicated in mechanosensing of several tissues, but are poorly explored in IVDs. METHODS: Primary human IVD cells from surgical biopsies composed of both annulus fibrosus and nucleus pulposus (passage 1-2) were exposed to simulated microgravity and to the TRPC channel inhibitor SKF-96365 (SKF) for up to 5 days. Proliferative capacity, cell cycle distribution, senescence and TRPC channel expression were analyzed. RESULTS: Both simulated microgravity and TRPC channel antagonism reduced the proliferative capacity of IVD cells and induced senescence. While significant changes in cell cycle distributions (reduction in G1 and accumulation in G2/M) were observed upon SKF treatment, the effect was small upon 3 days of simulated microgravity. Finally, downregulation of TRPC6 was shown under simulated microgravity. CONCLUSIONS: Simulated microgravity and TRPC channel inhibition both led to reduced proliferation and increased senescence. Furthermore, simulated microgravity reduced TRPC6 expression. IVD cell senescence and mechanotransduction may hence potentially be regulated by TRPC6 expression. This study thus reveals promising targets for future studies. These slides can be retrieved under Electronic Supplementary Material.

Expression and regulation of toll-like receptors (TLRs) in human intervertebral disc cells.

PURPOSE: Although inflammatory processes play an essential role in painful intervertebral disc (IVD) degeneration, the underlying regulatory mechanisms are not well understood. This study was designed to investigate the expression, regulation and importance of specific toll-like receptors (TLRs)--which have been shown to play an essential role e.g. in osteoarthritis--during degenerative disc disease. METHODS: The expression of TLRs in human IVDs was measured in isolated cells as well as in normal or degenerated IVD tissue. The role of IL-1ß or TNF-α in regulating TLRs (expression/activation) as well as in regulating activity of down-stream pathways (NF-κB) and expression of inflammation-related genes (IL-6, IL-8, HSP60, HSP70, HMGB1) was analyzed. RESULTS: Expression of TLR1/2/3/4/5/6/9/10 was detected in isolated human IVD cells, with TLR1/2/4/6 being dependent on the degree of IVD degeneration. Stimulation with IL-1ß or TNF-α moderately increased TLR1/TLR4 mRNA expression (TNF-α only), and strongly increased TLR2 mRNA expression (IL-1ß/TNF-α), with the latter being confirmed on the protein level. Stimulation with IL-1ß, TNF-α or Pam3CSK4 (a TLR2-ligand) stimulated IL-6 and IL-8, which was inhibited by a TLR2 neutralizing antibody for Pam3CSK4; IL-1ß and TNF-α caused NF-κB activation. HSP60, HSP70 and HMGB1 did not increase IL-6 or IL-8 and were not regulated by IL-1ß/TNF-α. CONCLUSION: We provide evidence that several TLRs are expressed in human IVD cells, with TLR2 possibly playing the most crucial role. As TLRs mediate catabolic and inflammatory processes, increased levels of TLRs may lead to aggravated disc degeneration, chronic inflammation and pain development. Especially with the identification of more endogenous TLR ligands, targeting these receptors may hold therapeutic promise.

Must we discontinue selective cervical nerve root blocks? Report of two cases and review of the literature.

We report two detrimental neurologic complications after technically correct selected cervical nerve root blocks. Based on these cases and a thorough review of the literature, the indication for cervical nerve root blocks was reconsidered and limited. Similarly, we modified our technique to further reduce the likelihood for the occurrence of such severe complications.

Inflammatory and catabolic signalling in intervertebral discs: the roles of NF-κB and MAP kinases.

Painful intervertebral disc disease is characterised not only by an imbalance between anabolic (i.e., matrix synthesis) and catabolic (i.e., matrix degradation) processes, but also by inflammatory mechanisms. The increased expression and synthesis of matrix metalloproteinases and inflammatory factors is mediated by specific signal transduction, in particular the nuclear factor-kappaB (NF-kB) and mitogen-activated protein kinase (MAPK)-mediated pathways. NF-kB and MAPK have been identified as the master regulators of inflammation and catabolism in several musculoskeletal disorders (e.g., osteoarthritis), and recently growing evidence supports the importance of these signalling pathways in painful disc disease. With continuing research exploiting in vitro and in vivo model systems to elucidate the roles of these pathways in disc degeneration, it may be possible in the near future to specifically target these major inflammatory / catabolic signalling pathways to treat painful degenerative disc disease. In this perspective, we aim to summarise the current state of knowledge concerning the inflammatory and catabolic molecular pathways of intervertebral disc disease (IDD), with a detailed description of NF-kB and MAP kinase-mediated signal transduction in disc cells. Furthermore, we will discuss the emerging novel molecular treatment modalities for IDD using pharmacological inhibitors targeting these pathways.

Human MMP28 expression is unresponsive to inflammatory stimuli and does not correlate to the grade of intervertebral disc degeneration.

BACKGROUND: MMP28 (epilysin) is a recently discovered member of the MMP (matrix metalloproteinase) family that is, amongst others, expressed in osteoarthritic cartilage and intervertebral disc (IVD) tissue. In this study the hypothesis that increased expression of MMP28 correlates with higher grades of degeneration and is stimulated by the presence of proinflammatory molecules was tested. Gene expression levels of MMP28 were investigated in traumatic and degenerative human IVD tissue and correlated to the type of disease and the degree of degeneration (Thompson grade). Quantification of MMP28 gene expression in human IVD tissue or in isolated cells after stimulation with the inflammatory mediators lipopolysaccharide (LPS), interleukin (IL)-1ß, tumor necrosis factor (TNF)-α or the histondeacetylase inhibitor trichostatin A was performed by real-time RT PCR. RESULTS: While MMP28 expression was increased in individual cases with trauma or disc degeneration, there was no significant correlation between the grade of disease and MMP28 expression. Stimulation with LPS, IL-1ß, TNF-α or trichostatin A did not alter MMP28 gene expression at any investigated time point or any concentration. CONCLUSIONS: Our results demonstrate that gene expression of MMP28 in the IVD is not regulated by inflammatory mechanisms, is donor-dependent and cannot be positively or negatively linked to the grade of degeneration and only weakly to the occurrence of trauma. New hypotheses and future studies are needed to find the role of MMP28 in the intervertebral disc.

Immunohistochemical identification of notochordal markers in cells in the aging human lumbar intervertebral disc.

The fate of notochord cells during disc development and aging is still a subject of debate. Cells with the typical notochordal morphology disappear from the disc within the first decade of life. However, the pure morphologic differentiation of notochordal from non-notochordal disc cells can be difficult, prompting the use of cellular markers. Previous reports on these notochordal cell markers only explored the occurrence in young age groups without considering changes during disc degeneration. The aim of this study, therefore, was to investigate presence, localization, and abundance of cells expressing notochordal cell markers in human lumbar discs during disc development and degeneration. Based on pilot studies, cytokeratins CK-8, -18 and -19 as well as Galectin-3 were chosen from a broad panel of potential notochordal cell markers and used for immunohistochemical staining of 30 human lumbar autopsy samples (0-86 years) and 38 human surgical disc samples (26-69 years). In the autopsy group, 80% of fetal to adolescent discs (0-17 years) and 100% of young adult discs (18-30 years) contained many cells with positive labeling. These cells were strongly clustered and nearly exclusively located in areas with granular changes (or other matrix defects), showing predominantly a chondrocytic morphology as well as (in a much lesser extent) a fibrocytic phenotype. In mature discs (31-60 years) and elderly discs (≥ 60 years) only 25 and 22-33%, respectively, contained few stained nuclear cells, mostly associated with matrix defects. In the surgical group, only 16% of samples from young adults (≤ 47 years) exhibited positively labeled cells whereas mature to old surgical discs (>47 years) contained no labeled cells. This is the first study describing the presence and temporo-spatial localization of cells expressing notochordal cell markers in human lumbar intervertebral discs of all ages and variable degree of disc degeneration. Our findings indicate that cells with a (immunohistochemically) notochord-like phenotype are present in a considerable fraction of adult lumbar intervertebral discs. The presence of these cells is associated with distinct features of (early) age-related disc degeneration, particularly with granular matrix changes.

Open mouth digital reduction of an odontoid synchondrosis fracture: a case report.

The "odontoid synchondrosis fracture" represents a rare but typical injury of the upper cervical spine in children less than 7 years. Conservative treatment with closed reduction and external fixation shows fusion rates across the synchondrosis in about 90% cases. When closed reduction cannot be achieved, open reduction and internal fixation is usually performed. We present the case of a girl aged 3 years and 5 months, whose closed reduction by passive manipulation of the head failed, but the same could successfully be achieved through transoral manipulation of the dens. After treatment with a Minerva plaster cast, the fracture was healed without complication. We suggest transoral manipulation in cases of otherwise irreducible "odontoid synchondrosis fracture." This technical hint may avoid unnecessary surgery in children with this type of injury.

The impact of economic evaluation on quality management in spine surgery.

Health care expenditures are substantially increasing within the last two decades prompting the imperative need for economic evaluations in health care. Historically, economic evaluations in health care have been carried out by four approaches: (1) the human-capital approach (HCA), (2) cost-effectiveness analysis (CEA), (3) cost-utility analysis (CUA) and (4) cost-benefit analysis (CBA). While the HCA cannot be recommended because of methodological shortcomings, CEA and CUA have been used frequently in healthcare. In CEA, costs are measured in monetary terms and health effects are measured in a non-monetary unit, e.g. number of successfully treated patients. In an attempt to develop an effectiveness measure that incorporates effects on both quantity and quality of life, so-called Quality Adjusted Life Years (QUALYs) were introduced. Contingent valuation surveys are used in cost-benefit analyses (CBA) to elicit the consumer's monetary valuations for program benefits by applying the willingness-to-pay approach. A distinguished feature of CBA is that costs and benefits are expressed in the same units of value, i.e. money. Only recently, economic evaluations have started to explore various spinal interventions particularly the very expensive fusion operations. While most of the studies used CEA or CUA approaches, CBAs are still rare. Most studies fail to show that sophisticated spinal interventions are more cost-effective than conventional treatments. In spite of the lack of therapeutic or cost-effectiveness for most spinal surgeries, there is rapidly growing spinal implant market demonstrating market imperfection and information asymmetry. A change can only be anticipated when physicians start to focus on the improvement of health care quality as documented by outcome research and economic evaluations of cost-effectiveness and net benefits.

Matrix metalloproteinase expression levels suggest distinct enzyme roles during lumbar disc herniation and degeneration.

The disruption of the extracellular disc matrix is a major hallmark of disc degeneration. This has previously been shown to be associated with an up-regulation of major matrix metalloproteinase (MMP) expression and activity. However, until now hardly any data are available for MMP/TIMP regulation and thereby no concept exists as to which MMP/TIMP plays a major role in disc degeneration. The objective of this study was, therefore, to identify and quantify the putative up-regulation of MMPs/TIMPs on the mRNA and protein level and their activity in disc material in relation to clinical data and histological evidence for disc degeneration. A quantitative molecular analysis of the mRNA expression levels for the MMPs (MMPs-1, -2, -3, -7, -8, -9, -13) and the MMP inhibitors (TIMPs-1 and -2) was performed on 37 disc specimens obtained from symptomatic disc herniation or degeneration. In addition, disc specimens from patients without disc degeneration/herniation (=controls) were analyzed. Expression of MMPs-1, -2, -3, -7, -8, -9, -13 and TIMPs-1, -2 was analyzed using quantitative RT-PCR, normalized to the expression level of a house keeping gene (GAPDH). Gene expression patterns were correlated with MMP activity (in situ zymography), protein expression patterns (immunohistochemistry), degeneration score (routine histology) and clinical data. MMP-3 mRNA levels were consistently and substantially up-regulated in samples with histological evidence for disc degeneration. A similar but less pronounced up-regulation was observed for MMP-8. This up-regulation was paralleled by the expression of TIMP-1 and to a lesser extent TIMP-2. In general, these findings could be confirmed with regard to protein expression and enzyme activity. This study provides data on the gene and protein level, which highlights the key role of MMP-3 in the degenerative cascade leading to symptomatic disc degeneration and herniation. Control of the proteolytic activity of MMP-3 may, therefore, come into the focus when aiming to develop new treatment options for early disc degeneration.

A cost-benefit analysis using contingent valuation techniques: a feasibility study in spinal surgery.

OBJECTIVES: To carry out a pilot study to demonstrate the feasibility of the contingent valuation (CV) approach to identify net benefits gained from spinal interventions; and to conduct a formal cost-benefit analysis (CBA) using a retrospective study design. The study design is a CBA feasibility study using a CV survey with ex post willingness-to-pay/willingness-to-accept (WTP/WTA) questions. The CBA study was carried out in the specialty of spinal surgery. SUMMARY OF BACKGROUND DATA: Although increasing data are gathered on the societal costs of low back pain, little information is available on how patients "value" the benefits of surgery or whether interventions in this area are indeed cost-beneficial. CV surveys are used in CBA to elicit the consumer's monetary valuations for program benefits. MATERIALS AND METHODS: A total of 115 patients after lumbar fusion, discectomy, or decompression were asked to respond to an ex post questionnaire on their WTP/WTA for their respective intervention. Additional questions addressed socio-demographics, household income, and clinical outcome. WTP/WTA was related to the actual intervention costs and clinical outcome. The WTP and cost data were then combined within a formal CBA framework with associated 95% confidence intervals generated using bootstrapping methods. RESULTS: The response rate was 91.3% (n = 105). 89.5% were satisfied/very satisfied with the treatment. 76.2% found the result of the operation was good/excellent and 75.7% would choose the operation for a given hypothetical intervention cost. Mean stated WTP was 20% lower than the actual operation costs (not known to respondents) for spinal fusion, although it was 37% higher for discectomy and 10% higher for decompression. The individuals' financial situation was the strongest predictor for WTP. Pain improvement, present pain, duration of hospitalization, and estimated intervention costs were significant independent predictors in the expected direction for the WTP, having controlled for socio-demographic and financial confounding variables. CONCLUSION: This study explored the feasibility of the CV approach for spinal interventions. The approach produced results suggesting positive net benefits with their associated levels of variability for discectomy and decompression, indicating that such surgery is cost-beneficial within a CBA framework, but this conclusion is not supported in the case of spinal fusion. Nevertheless, to improve reliability of the net-benefit estimates for these interventions, we recommend further studies comparing in particular ex ante and ex post WTP methods.

Treatment Efficacy, Clinical Utility, and Cost-Effectiveness of Multidisciplinary Biopsychosocial Rehabilitation Treatments for Persistent Low Back Pain: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: To review the current literature on the treatment efficacy, clinical utility, and cost-effectiveness of multidisciplinary biopsychosocial rehabilitation (MBR) for patients suffering from persistent (nonspecific) lower back pain (LBP) in relation to pain intensity, disability, health-related quality of life, and work ability/sick leave. METHODS: We carried out a systematic search of Web of Science, Cochrane Library, PubMed Central, EMBASE, and PsycINFO for English- and German-language literature published between January 2010 and July 2017. Study selection consisted of exclusion and inclusion phases. After screening for duplication, studies were excluded on the basis of criteria covering study design, number of participants, language of publication, and provision of information about the intervention. All the remaining articles dealing with the efficacy, utility, or cost-effectiveness of intensive (more than 25 hours per week) MBR encompassing at least 3 health domains and cognitive behavioral therapy-based psychological education were included. RESULTS: The search retrieved 1199 publications of which 1116 were duplicates or met the exclusion criteria. Seventy of the remaining 83 articles did not meet the inclusion criteria; thus 13 studies were reviewed. All studies reporting changes in pain intensity or disability over 12 months after MBR reported moderate effect sizes and/or p-values for both outcomes. The effects on health-related quality of life were mixed, but MBR substantially reduced costs. Overall MBR produced an enduring improvement in work ability despite controversy and variable results. CONCLUSIONS: MBR is an effective treatment for nonspecific LBP, but there is room for improvement in cost-effectiveness and impact on sick leave, where the evidence was less compelling.

Analysis of tissue distribution of TNF-alpha, TNF-alpha-receptors, and the activating TNF-alpha-converting enzyme suggests activation of the TNF-alpha system in the aging intervertebral disc.

We immunohistochemically analyzed the expression and localization of TNF-alpha, its receptors TNF-RI and -RII, and the TNF-alpha-activating enzyme TACE in human autopsy (n=63) and surgical (n=35) lumbar intervertebral disc samples. In parallel, the TNF-alpha-mRNA was quantified by reverse transcriptase-polymerase chain reaction (RT-PCR). All samples were morphometrically evaluated for the proportion of positively labeled cells in the different anatomical regions of the disc. We detected a significant and comparable expression of all four parameters beginning in young adult age (c. 18 years) and being most extensive in the nucleus pulposus. This level was slightly reduced in older age discs. The annulus fibrosus contained significantly less labeled cells. In accord, the number of TNF-alpha-transcripts was elevated in most cases with immunohistochemical TNF-alpha expression. We provide clear evidence that TNF-alpha is expressed in discs of increasing age, which correlates with histomorphological signs of disc degeneration. In consequence, TNF-alpha seems to be activated (by the converting enzyme TACE) and biologically active through its receptors in human lumbar disc tissue.

Immunomorphological analysis of RAGE receptor expression and NF-kappaB activation in tissue samples from normal and degenerated intervertebral discs of various ages.

We immunohistochemically investigated the pattern of RAGE expression and NFkappaB translocation into the nucleus in 43 complete cross-sections of human lumbar intervertebral discs (neonatal-85 years) and compared this with the carboxymethyl-lysine (CML) modification of proteins as a marker for oxidative stress. No significant expression of RAGE, no obvious activation of NF-kappaB, and no deposition of CML-modified proteins were seen in fetal, juvenile, and young adolescent discs (until age of 13 years). In adults, 25-50% of nucleus pulposus cells were labeled for RAGE and activated NF-kappaB, which correlated well with the occurrence and extent of CML staining in the pericellular matrix. In the annulus fibrosus significantly lower values were seen than in the nucleus pulposus. In consequence, we provide evidence for activation of the NF-kappaB system in intervertebral discs in vivo, which correlates with accumulated oxidative stress and increases in age and disc degeneration. Oxidative stress (as monitored by CML modifications) may lead to RAGE activation and NF-kappaB translocation.

Long-term clinical and radiographic results of Cotrel-Dubousset instrumentation of right thoracic adolescent idiopathic scoliosis.

Little substantive data is available in the literature on the long-term clinical and radiological results of Cotrel-Dubousset instrumentation (CDI) for the treatment of adolescent idiopathic scoliosis. We therefore retrospectively investigated the long-term clinical and radiographic outcome of patients who underwent (CDI) for right thoracic adolescent idiopathic scoliosis. 54 consecutive patients (45 females, 9 males) who underwent CDI for right thoracic adolescent idiopathic scoliosis with an average age of 14 years (range 10-21 years) at surgery were included in this series. There were 18 King Type II, 19 Type III, 5 Type IV, 3 Type V and 9 double major curves. The average coronal Cobb angle of the primary thoracic curve preoperatively, postoperatively and at latest follow-up was 55 degrees, 17 degrees and 22 degrees, respectively. The lumbar curve (secondary and double major) averaged 40 degrees, 21 degrees and 23 degrees, respectively. Coronal balance (deviation from the central sacral line) was slightly improved from 13 mm to 11 mm. The average shoulder elevation increased from 3 degrees to 5 degrees, presumably as a result of the rod derotation maneuver. Thoracic kyphosis (20 degrees to 22 degrees) and lumbar lordosis (49 degrees to 54 degrees) was preserved or even improved by the instrumentation. All patients were doing well and had no complaints with regard to a substantial limitation of professional or sports activity. There were no apparent non-unions, infections or neurological complications. CDI of adolescent right thoracic idiopathic scoliosis provides encouraging clinical and radiographic results at an average follow-up of 9 years (2 to 16 years). Overall patient satisfaction, functional status and subjective cosmetic improvement is high.

Development and Validation of the iDI: A Short Self-Rating Disability Instrument for Low Back Pain Disorders.

STUDY DESIGN: Cross-sectional and longitudinal validation study. OBJECTIVE: Development and validation of a short, reliable, and valid questionnaire for the assessment of low back pain-related disability. METHODS: The iDI was created in a stepwise procedure: (1) its development was based on the literature and theoretical consideration; (2) outcome data were collected and evaluated in a pilot study; (3) final validations were performed based on an international multicenter spine surgery outcome study including 514 patients; (4) the iDI was programmed for a tablet computer (iPad) and tested for its clinical practicability. RESULTS: The final version of the iDI comprises of 8 simple questions related to different aspects of disability with a 5-point Likert-type answer scale. The iDI compared very well to the Oswestry Disability Index in terms of reliability and validity. The iDI was demonstrated to be suitable for data assessment on a tablet computer (iPad). CONCLUSIONS: The iDI is a short, valid, and practicable tool that facilitates routine quality assessment in terms of low back pain-related disability.

Effect of aging and degeneration on disc volume and shape: A quantitative study in asymptomatic volunteers.

Debate continues on the effect of disc degeneration and aging on disc volume and shape. So far, no quantitative in vivo MRI data is available on the factors influencing disc volume and shape. The objective of this MRI study was to quantitatively investigate changes in disc height, volume, and shape as a result of aging and/or degeneration omitting pathologic (i.e., painful) disc alterations. Seventy asymptomatic volunteers (20-78 years) were investigated with sagittal T1- and T2-weighted MR-images encompassing the whole lumbar spine. Disc height was determined by the Dabbs method and the Farfan index. Disc volume was calculated by the Cavalieri method. For the disc shape the "disc convexity index" was calculated by the ratio of central disc height and mean anterior/posterior disc height. Disc height, disc volume, and the disc convexity index measurements were corrected for disc level and the individuals age, weight, height, and sex in a multilevel regression analysis. Multilevel regression analysis showed that disc volume was negatively influenced by disc degeneration (p < 0.001) and positively correlated with body height (p < 0.001) and age (p < 0.01). Mean disc height and the disc convexity index were negatively influenced by disc degeneration but not by gender, weight, and height. Disc height was positively correlated with age (p < 0.01). From the results of this study, it can be concluded that disc degeneration generally results in a decrease of disc height and volume as well as a less convex disc shape. In the absence of disc degeneration, however, age tends to result in an inverse relationship on disc height, volume, and shape.

Therapeutic efficacy of facet joint blocks.

OBJECTIVE: The objective of our study was to investigate outcome predictors of short- and medium-term therapeutic efficacy of facet joint blocks. MATERIALS AND METHODS: Forty-two patients with chronic lower back pain who were undergoing facet joint blocks at one (n = 29) or two (n = 13) levels were analyzed. All patients underwent MRI or CT of the lumbar spine within 5 months before the facet joint blocks. The facet joint blocks were performed under fluoroscopic guidance. A small amount (< 0.3 mL) of iodinated contrast agent, 0.5 mL of local anesthetics and 0.5 mL of steroids, were injected. The initial pain response was prospectively assessed using a visual analogue scale. Additional data, including short-term effect (> 1 week) and medium-term effect (> 3 months), were collected by a structured telephone interview. CT and MRI were reviewed with regard to the extent of facet joint abnormalities. Multiple logistic regression analyses were conducted to identify outcome predictor for efficacy of facet joint blocks. RESULTS: A positive immediate effect was seen in 31 patients (74%). A positive medium-term effect was found in 14 patients (33%). Pain alleviated by motion (p = 0.035) and the absence of joint-blocking sensation (p = 0.042) predicted pain relief. However, the extent of facet joint osteoarthritis on MRI and CT was not a significant predictor for outcome (p = 0.57-0.95). CONCLUSION: Facet joint blocks appear to have a beneficial medium-term effect in one third of patients with chronic lower back pain and may therefore be a reasonable adjunct to nonoperative treatment. However, outcome appears to depend on clinical, not on morphologic, imaging findings.

Laser-induced thermotherapy of the vertebral body: preliminary assessment of safety and real-time magnetic resonance monitoring in an animal model.

RATIONALE AND OBJECTIVES: To evaluate the safety of percutaneous laser-induced thermotherapy (LITT) of vertebral bodies and the feasibility of monitoring the thermal effects with real-time magnetic resonance (MR) imaging. MATERIALS AND METHODS: Laser fibers were placed in nine vertebral bodies of two minipigs under CT-guidance. LITT was performed in an open 0.5 T MR scanner using an Nd: YAG laser source. A T1-weighted MR sequence was used for continuous color-coded temperature monitoring. Histology of the vertebral body and spinal cord were subsequently obtained. RESULTS: Thermal lesions of the vertebral bodies measured 8 to 11 mm (mean 9.3 mm) in diameter. Thermal injuries of the spinal cord were observed in all four levels in which cortical bone surrounding the spinal canal was damaged during needle placement and in none with intact cortical bone. MR monitoring of the thermal effect was possible only if acquired in breath-hold technique. CONCLUSIONS: An intact cortical bone seems to be a prerequisite for safe LITT of the vertebral body. Real-time MR-monitoring of the thermal effect in vertebral bodies and the spinal canal was feasible with breath-hold acquisition. Larger studies are necessary to further evaluate accuracy of real-time MR imaging.

Transcranial electrical stimulation: significance of fast versus slow charge delivery for intra-operative monitoring.

OBJECTIVES: Motor-evoked potentials (MEP) for intra-operative monitoring due to fast charge (fc: 1.0 Coulomb/s) and slow charge (sc: 0.1Coulomb/s) delivery for multipulse transcranial electrical stimulation (TES) were compared. METHODS: MEPs due to fc (n=162) and sc stimulation (n=182) were performed in parallel in a prospective study. The fc stimulation technique is characterized by an increased steepness of charge delivery with consequent reduction of stimulus duration of 50 micros compared to 500 micros in sc stimulation. Stimulation charges (C=Coulomb) and MEP parameters during spine surgery were analyzed. RESULTS: MEPs were successfully recorded in 15/18 patients under total intravenous anesthesia. The mean charge to induce intra-operative MEPs (stimulation threshold) was significantly less in fc (0.195 mC) as compared to sc stimulation (0.298 mC). With both stimulation techniques, in all patients without impairment of motor function, MEPs could be recorded and no technique was superior with respect to successful stimulation. The mean MEP latencies, amplitudes and the extent of intra-individual variation of MEP parameters during surgery (shift of latency less than 10%, variability of amplitude less than 50%) were not different with both stimulation techniques. CONCLUSIONS: TES with either fc or sc stimulation can be used reliably for intraoperative monitoring. Fc and sc stimulation are comparable with respect to feasibility, intra-individual variability and mean parameters of MEP responses. However, fc stimulation provides a higher stimulation efficiency and requires about 35% less total charge for MEP monitoring.