The contradictory effect of macrophage-related cytokine expression in lumbar disc herniations: a systematic review

Purpose Sciatic symptoms due to lumbar disc herniation are likely to be caused not solely by mechanical compression of the nerve root, but also by pain-inducing elements from inflammatory processes. Key components in the inflammatory reaction are M1 and M2 macrophages, with the M1 type being associated with pro-inflammatory processes and M2 with anti-inflammatory-processes. Method The present systematic review summarizes all studies on associations between M1 and M2 macrophages and their related inflammation factors and pain symptoms in lumbar disc herniations. Literature search was performed using an optimally sensitive search string. Studies were selected for inclusion by means of predefined inclusion and exclusion criteria and subsequently graded for risk of bias. A total of 14 studies were included. Overall risk of bias was moderate (8/14), and three studies had high risk of bias and three has low risk of bias. Results Regarding M1-related cytokines, high levels of TNF-alpha, TNFR1, IL-6, IL-8, and IFN-gamma were all associated high VAS scores. In contrast, high levels of TNFR2 were associated with lower VAS scores. Moreover, no associations were found for IL-1a and IL-1 beta. Results regarding M2-related cytokines revealed the opposite: high levels of both IL-4 and IL-10 were associated with lower VAS scores. No associations were established for TGF-beta. Moreover, the presence of macrophages (CD68) was negatively associated with VAS scores. Conclusion While M1-related pro-inflammatory cytokines worsen pain symptoms, M2-related anti-inflammatory cytokines alleviate pain symptoms. Nevertheless, the present evidence is limited, and further research on the underlying pathophysiological mechanism in sciatica is required. Graphic abstract These slides can be retrieved under Electronic Supplementary Material.Nephrolog

Decompression with or without concomitant fusion in lumbar stenosis due to degenerative spondylolisthesis: a systematic review

PURPOSE:The primary objective of this systematic review is to compare the outcome after decompression with and without concomitant instrumented fusion in patients with lumbar stenosis and degenerative spondylolisthesis. Does adding fusion to simple decompression lead to better results?METHODS:PubMed, Embase, CENTRAL, Cochrane, Web of Science, CINAHL and Academic Search Premier were searched. All studies comparing outcome of decompression alone to decompression with concomitant-instrumented fusion in patients suffering from symptomatic lumbar stenosis with degenerative spondylolisthesis were included. Risk of bias was assessed using an adapted version of the Cowley checklist.RESULTS:Eleven studies were included in the analysis involving 3119 patients in total. In the majority of studies, including two RCTs, clinical outcome of both patient groups was comparable regarding most clinical outcome measures.CONCLUSION:Currently there is not enough evidence that adding instrumented fusion to a decompression leads to superior outcomes compared to decompression only in patients with lumbar stenosis and degenerative spondylolisthesis. The most important clinical outcome measures, including the ODI, show comparable results. Therefore, the least invasive and least costly procedure, being decompression alone, is preferred in patients with low-grade spondylolisthesis with predominant leg pain. These slides can be retrieved under Electronic Supplementary Material.Stem cells & developmental biolog

Modic changes in the lumbar spine: exploring their association with abdominal aortic calcification as a potential indicator of systemic arherosclerosis

BackgroundThis was a cross-sectional study on the correlation between abdominal aortic calcification (AAC) and Modic changes (MC). Little is known regarding the etiology of MC in the lumbar spine. Currently, insufficient vascularization of the endplate has been proposed to contribute to the appearance of MC. Our objective was to investigate whether AAC, a marker for a poor vascular status, is associated with MC in patients suffering from degenerative disc disease.MethodsRadiologic images of patients (n = 130) suffering from degenerative lumbar disc disease were reviewed. Type and severity of MC were assessed using magnetic resonance images, and severity of AAC was evaluated using computed tomography images or fluoroscopy. Both items were dichotomized into minimal and relevant grades. The correlation between them was studied using Spearman's correlation test, with age as a covariate.ResultsOf the patients, 113 (87%) demonstrated MC (31% type I, 63% type II, and 6% type III) (55% relevant grade), and 68% had AAC (44% relevant grade). Spearman statistical analysis revealed that AAC was correlated with age (P P = 0.142). AAC severity was significantly correlated with MC, remaining so after age adjustment (P P = 0.015); however, this association lost significance after adjusting for age (P = 0.057).ConclusionsAAC and MC (mainly MC type II) are associated, indicating that reduced blood supply or even a poor systemic vascularization status due to atherosclerotic disease may play a role in the formation of MC. Future studies focusing on the etiology of MC should pay more attention to patients' vascular status and determinants of abdominal aorta calcification.Afdeling Klinische Chemie en Laboratoriumgeneeskunde (AKCL

Epidural steroid compared to placebo injection in sciatica: a systematic review and meta-analysis

Purpose The purpose of this systematic review and meta-analysis was to determine whether epidural steroid injections (ESI) are superior to epidural or non-epidural placebo injections in sciatica patients. Methods The PubMed, Embase, Cochrane Library, and Web of science databases were searched for trials comparing ESI to epidural or non-epidural placebo. Risk of bias was assessed using the Cochrane RoB 2 tool. The primary outcome measures were pooled using a random-effects model for 6-week, 3-month, and 6-month follow-up. Secondary outcomes were described qualitatively. Quality of evidence was graded using GRADE classification. Results Seventeen out of 732 articles were included. ESI was superior compared to epidural placebo at 6 weeks (- 8.6 [- 13.4; - 3.9]) and 3 months (- 5.2 [- 10.1; - 0.2]) for leg pain and at 6 weeks for functional status (- 4.1 [- 6.5; - 1.6]), though the minimally clinical important difference (MCID) was not met. There was no difference in ESI and placebo for back pain, except for non-epidural placebo at 3 months (6.9 [1.3; 12.5]). Proportions of treatment success were not different. ESI reduced analgesic intake in some studies and complication rates are low. Conclusion The literature indicates that ESI induces larger improvements in pain and disability on the short term compared to epidural placebo, though evidence is of low to moderate quality and MCID is not met. Strong conclusions for longer follow-up or for comparisons with non-epidural placebo cannot be drawn due to general low quality of evidence and limited number of studies. Epidural injections can be considered a safe therapy.Neuro Imaging Researc

Symptomatic lumbar stenosis due to low-grade degenerative spondylolisthesis can effectively be treated with mere decompression

PurposeAdding instrumented spondylodesis to decompression in symptomatic spinal stenosis with degenerative spondylolisthesis is subject of debate. The presence of spondylolisthesis due to degeneration is an indicator of severe facet joint and intervertebral disc degeneration, and this may fit increased instability of the spine. We aim to establish the incidence of degenerative spondylolisthesis in spinal stenosis surgical candidates and to evaluate the incidence of failure of decompressive surgery without concomitant spondylodesis as initial treatment.MethodsMedical files of all operated patients for spinal stenosis between 2007 and 2013 were evaluated. Demographic characteristics, pre-operative radiological characteristics (level of stenosis, presence, and grade of spondylolisthesis), surgical technique, incidence, and indication for reoperation were summarised, as well as the type of reoperation. Patient satisfaction was classified as 'satisfied' or 'unsatisfied' after initial and secondary surgery. The follow-up was 6 to 12 years.ResultsNine hundred thirty-four patients were included, and 253 (27%) had a spondylolisthesis. Seventeen percent of the spondylolisthesis patients receiving decompression were reoperated versus 12% of the stenosis patients (p=.059). Reoperation in the spondylolisthesis group concerned instrumented spondylodesis in 38 versus 10% in the stenosis group. The satisfaction percentage was comparable in the stenosis and the spondylolisthesis group two months after surgery (80 vs. 74%). Of the 253 spondylolisthesis patients, 1% initially received instrumented spondylodesis and 6% in a second operation.ConclusionLumbar stenosis with and without (low-grade) degenerative spondylolisthesis can usually effectively be treated with mere decompression. Instrumented surgery in a second surgical procedure does not lead to less satisfaction with surgical outcomes.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Discussing reproductive health in spinal care, part II: fertility issues

Abstract PURPOSE: Due to advancing insights, discussing fertility in spinal care is an emerging topic. Studies among neurosurgeons to evaluate clinical practice about discussing fertility are non-existent. The aim of this study is to review knowledge, attitude and practice patterns regarding discussing fertility in spinal care. METHODS: Dutch neurosurgeons and residents were sent a mail-based questionnaire addressing attitude, knowledge and practice patterns regarding discussing fertility. RESULTS: Response rate was 62 % (compared to mean of 28 % in similar surveys) with 89 questionnaires suitable for analysis. Mean age was 42 years with 83 % of respondents being male. A quarter of respondents stated neurosurgeons are responsible to discuss fertility, with 12 % indicating to actually do this. Fertility is discussed more often with patients with cauda equina syndrome (70 %) and with men (p = 0.006). Merely 8 % of respondents stated to have adequate knowledge on fertility preservation (FP); this percentage was higher for doctors with spinal surgery as specialty (p = 0.015). In case of cauda equina syndrome, doctors with more knowledge discussed fertility more often (p = 0.002). Fifty-three percent of neurosurgeons wished to enhance their knowledge, in order to feel more comfortable to discuss fertility with their patients. Five percent indicated to have ever referred a patient to a fertility specialist. CONCLUSION: With the exception of cauda equina syndrome, fertility is not routinely discussed in spinal care. Fertility is discussed more often with men. Recent guidelines state that discussing fertility is an essential part of good practice in spinal care. Education on fertility and FP needs to be integrated in the neurosurgical training program to create more awareness, and to enable clinicians to provide adequate information and care to the patient. KEYWORDS: Education; Fertility; Practice patterns; Reproductive health; Spinal care GynecologyCervix cance

The optimal treatment of type II and III odontoid fractures in the elderly: an updated meta-analysis

PurposeOdontoid fractures are the most common cervical spine fractures in the elderly, with a controversial optimal treatment. The objective of this review was to compare the outcome of surgical and conservative treatments in elderly (& GE; 65 years), by updating a systematic review published by the authors in 2013.MethodsA comprehensive search was conducted in seven databases. Clinical outcome was the primary outcome. Fracture union- and stability were secondary outcomes. Pooled point estimates and their respective 95% confidence intervals (CIs) were derived using the random-effects model. A random-effects multivariable meta-regression model was used to correct for baseline co-variates when sufficiently reported.ResultsForty-one studies met the inclusion criteria, of which forty were case series and one a cohort study. No clinical differences in outcomes including the Neck Disability Index (NDI, 700 patients), Visual Analogue Scale pain (VAS, 180 patients), and Smiley-Webster Scale (SWS, 231 patients) scores were identified between surgical and conservative treatments. However, fracture union was higher in surgically treated patients (pooled incidence 72.7%, 95% CI 66.1%, 78.5%, 31 studies, 988 patients) than in conservatively treated patients (40.2%, 95% CI 32.0%, 49.0%, 22 studies, 912 patients). This difference remained after correcting for age and fracture type. Fracture stability (41 studies, 1917 patients), although numerically favoring surgery, did not appear to differ between treatment groups.ConclusionWhile surgically treated patients showed higher union rates than conservatively treated patients, no clinically relevant differences were observed in NDI, VAS pain, and SWS scores and stability rates. These results need to be further confirmed in well-designed comparative studies with proper adjustment for confounding, such as age, fracture characteristics, and osteoporosis degree.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Effectiveness and cost-effectiveness of rehabilitation after lumbar disc surgery (REALISE): design of a randomised controlled trial

Background: Patients who undergo lumbar disc surgery for herniated discs, are advocated two different postoperative management strategies: a watchful waiting policy, or referral for rehabilitation immediately after discharge from the hospital. A direct comparison of the effectiveness and cost-effectiveness of these two strategies is lacking. Methods/Design. A randomised controlled trial will be conducted with an economic evaluation alongside to assess the (cost-) effectiveness of rehabilitation after lumbar disc surgery. Two hundred patients aged 18-70 years with a clear indication for lumbar disc surgery of a single level herniated disc will be recruited and randomly assigned to either a watchful waiting policy for first six weeks or exercise therapy starting immediately after discharge from the hospital. Exercise therapy will focus on resumption of activities of daily living and return to work. Therapists will tailor the intervention to the individual patient's needs. All patients will be followed up by the neurosurgeon six weeks postoperatively. Main outcome measures are: functional status, pain intensity and global perceived recovery. Questionnaires will be completed preoperatively and at 3, 6, 9, 12 and 26 weeks after surgery. Data will be analysed according to the intention-to-treat principle, using a linear mixed model for continuous outcomes and a generalised mixed model for dichotomous outcomes. The economic evaluation will be performed from a societal perspective. Discussion. The results of this trial may lead to a more consistent postoperative strategy for patients who will undergo lumbar disc surgery. Trial registration. Netherlands Trial Register: NTR3156. © 2013 Oosterhuis et al.; licensee BioMed Central Ltd

Study protocol: effect of infection, Modic and inflammation on clinical outcomes in surgery for radiculopathy (EIMICOR)

Background: Evidence indicates that inflammatory processes are involved in radicular pain as well as in resorption of herniated disc tissue. Furthermore there are indications that the presence of vertebral end plate pathology (Modic changes; MC) is associated with a negative effect on inflammation. It is hypothesized that in patients with MC, the (possibly bacterial induced) inflammation will be accompanied by pro inflammatory cytokines that worsen the outcome, and that in patients without MC, the inflammation is accompanied by cytokines that induce a resorption process to accelerate recovery.Methods: This prospective cohort study will include 160 lumbar and 160 cervical patients (total of 320), which are scheduled for surgery for either a lumbar or cervical herniated disc with ages between 18 and 75. The main and interaction effects of local bacterial infection (culture), inflammatory cells in disc material (immunohistology), MC (MRI), and blood biomarkers indicating inflammation or infection (blood sample evaluation) will be evaluated. Clinical parameters to be evaluated are leg pain on the 11 point NRS pain scale, Oswestry (lumbar spine) or Neck (cervical spine) Disability Index, Global Perceived Recovery, Womac Questionnaire, and medication status, at baseline, and after 6, 16, 26 and 52 weeks.Discussion: Gaining insight in the aetiology of pain and discomfort in radiculopathy caused by a herniated disc could lead to more effective management of patients. If the type of inflammatory cells shows to be of major influence on the rate of recovery, new immunomodulating treatment strategies can be developed to decrease the duration and intensity of symptoms. Moreover, identifying a beneficial inflammatory response in the disc through a biomarker in blood could lead to early identification of patients whose herniations will resorb spontaneously versus those that require surgery.OV

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Scientific Assessment and Innovation in Neurosurgical Treatment Strategie