Machine learning for image analysis in the cervical spine: Systematic review of the available models and methods.

•Neural network approaches show the most potential for automated image analysis of thecervical spine.•Fully automatic convolutional neural network (CNN) models are promising Deep Learning methods for segmentation.•In cervical spine analysis, the biomechanical features are most often studied using finiteelement models.•The application of artificial neural networks and support vector machine models looks promising for classification purposes.•This article provides an overview of the methods for research on computer aided imaging diagnostics of the cervical spine.

Exploring macrophage differentiation and its relation to Modic changes in human herniated disc tissue.

Introduction: Cervical- and lumbosacral radiculopathy symptoms due to disc herniation are likely to be influenced by macrophage infiltration of the herniated disc. Vertebral endplate changes are hypothesized to, at least partially, correlate to the inflammatory condition of the disc and its environment. Research question: The present study aims to evaluate several immunohistochemical M1-and M2-markers for their suitability to discern pro-inflammatory M1-and anti-inflammatory M2 macrophage differentiation patterns in herniated intervertebral disc tissue. In addition, their associations with Modic changes (MC) of the vertebral endplates will be evaluated. Materials and methods: Herniated disc samples were collected from 45 patients undergoing surgery for cervical- or lumbosacral radiculopathy. Samples were processed for immunohistochemistry and stained for the presence of macrophages: CD68 (macrophage marker), CD40 (M1), iNOS (M1), CD192 (M1), CD163 (M2), Arg1 (M2) and CD209 (M2). T-cells (CD3) and neutrophil (CD15) expressions were studied additionally. Results: CD68 positive cells were present with a median density of 50/cm2, M2 markers CD163 and CD209 were expressed most dominantly, followed by M1 marker CD192. Other M1/M2 markers, T-cell and neutrophil expression was limited. Lumbar samples showed higher expression of iNOS and Arg1 compared to cervical samples. Presence of Modic changes was associated with higher levels of CD68+ cells (p â€‹= â€‹0.046), but no significant differences in M1/M2 markers were found. Discussion and conclusion: For studying M1 macrophages, CD192 is the most suitable marker due to its high expression; whereas for M2 macrophages, this is CD163 due to its high expression and selectivity. Further, the relatively high expression of M2 markers indicates predominance of anti-inflammatory over pro-inflammatory macrophages in symptomatic lumbar and cervical disc herniations. No associations between M1/M2 markers and MC were seen in this limited number of samples. In order to further explore the role of macrophage differentiation and its relation with MC in radiculopathy, a large prospective trial with elaborate clinical follow-up is required.

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.

Lumbar disc extrusions reduce faster than bulging discs due to an active role of macrophages in sciatica.

OBJECTIVE: This retrospective observational histological study aims to associate the size and type of disc herniation with the degree of macrophage infiltration in disc material retrieved during disc surgery in patients with sciatica. METHODS: Disc tissue of 119 sciatica patients was embedded in paraffin and stained with hematoxylin and CD68. Tissue samples were categorized as mild (0-10/cm2), moderate (10-100/cm2), and considerable (> 100/cm2) macrophage infiltration. All 119 patients received an MRI at baseline, and 108 received a follow-up MRI at 1-year. MRIs were reviewed for the size and type of the disc herniations, and for Modic changes in the vertebral endplates. RESULTS: Baseline characteristics and duration of symptoms before surgery were comparable in all macrophage infiltration groups. The degree of macrophage infiltration was not associated with herniation size at baseline, but significantly associated with reduction of size of the herniated disc at 1-year post surgery. Moreover, the degree of macrophage infiltration was higher in extrusion in comparison with bulging (protrusion) of the disc. Results were comparable in patients with and without Modic changes. CONCLUSION: Macrophage infiltration was positively associated with an extruded type of disc herniation as well as the extent of reduction of the herniated disc during 1-year follow-up in patients with sciatica. This is an indication that the macrophages play an active role in reducing herniated discs. An extruded disc herniation has a larger surface for the macrophages to adhere to, which leads to more size reduction.

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-α, TNFR1, IL-6, IL-8, and IFN-γ 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-1ß. 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-ß. 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. These slides can be retrieved under Electronic Supplementary Material.

Evaluation of bony fusion after anterior cervical discectomy: a systematic literature review.

PURPOSE: Anterior cervical discectomy and fusion (ACDF) has proven effective in treating radicular arm pain. Post-operatively, cervical spine stability is temporarily challenged, but data on bony fusion and speed of fusion are ambiguous; optimum evaluation method and criteria are debated. AIM: To study bony fusion accomplishment and to obtain an overview of methods to evaluate fusion. METHODS: A literature search was performed in PubMed and Embase. Included studies had to report original data concerning 1- or 2-level ACDF with intervertebral device or bone graft, where bony fusion was assessed using CT scans or X-rays. RESULTS: A total of 146 articles comprising 10,208 patients were included. Bony fusion was generally defined as "the presence of trabecular bridging" and/or "the absence of motion". Fusion was accomplished in 90.1% of patients at the final follow-up. No gold standard for assessment could be derived from the results. Addition of plates and/or cages with screws resulted in slightly higher accomplishment of fusion, but differences were not clinically relevant. Eighteen studies correlated clinical outcome with bony fusion, and 3 found a significant correlation between accomplishment and better clinical outcome. CONCLUSIONS: In approximately 90% of patients, bony fusion is accomplished one year after ACDF. As there is no generally accepted definition of bony fusion, different measuring techniques cannot be compared to a gold standard and it is impossible to determine the most accurate method. Variations in study design hamper conclusions on optimising the rate of bony fusion by choice of material and/or additives. Insufficient attention is paid to correlation between bony fusion and clinical outcome. These slides can be retrieved from electronic supplementary material.

Chordoma: a systematic review of the epidemiology and clinical prognostic factors predicting progression-free and overall survival.

BACKGROUND AND AIMS: The aim of this systematic review is to describe the epidemiology of chordoma and to provide a clear overview of clinical prognostic factors predicting progression-free and overall survival. METHODS: Four databases of medical literature were searched. Separate searches were performed for each of the two objectives. Reference and citation tracking was performed. Papers were processed by two independent reviewers according to a protocol that included risk of bias analysis. Disagreement was resolved by discussion. Pooled analyses were planned if homogeneity of data would allow. RESULTS: Incidence-incidence rates ranged between 0.18 and 0.84 per million persons per year and varied between countries and presumably between races. On average patients were diagnosed in their late fifties and gender data indicate clear male predominance. Two of the largest studies (n = 400 and n = 544) reported different anatomical distributions: one reporting the skull base and sacrococcygeal area affected in 32% and 29% of cases, whereas the other reporting that they were affected in 26% and 45% of cases, respectively. PROGNOSTIC FACTORS: Statistically significant adverse prognostic factors predicting progression-free and overall survival include female sex, older age, bigger tumour size, increasing extent of tumour invasion, non-total resection, presence of metastasis, local recurrence, and dedifferentiated histological subtype. CONCLUSIONS: Incidence rate and anatomical distribution vary between countries and presumably between races. Most chordomas arise in the skull base and sacrococcygeal spine, and the tumour shows clear male predominance. Multiple adverse prognostic factors predicting progression-free and overall survival were identified in subgroups of patients. These slides can be retrieved under Electronic Supplementary Material.

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.

Cauda Equina Syndrome: presentation, outcome, and predictors with focus on micturition, defecation, and sexual dysfunction.

BACKGROUND: Even though micturition, defecation, and sexual function are substantially affected in cauda equina syndrome (CES), data on outcome are scarce. METHODS: Medical files of patients operated on lumbar herniated disc were screened for CES and retrospectively analyzed for baseline characteristics, outcome of micturition, defecation, and sexual function and possible predictors. RESULTS: Seventy-five CES patients (52% men) were included with a mean age of 44 years. L5-S1 was the most common affected level. Duration of CES complaints at presentation was, on average, 84 h (median 48 h). Prevalence of symptoms at presentation: sciatica (97%), altered sensation of the saddle area (93%), micturition dysfunction (92%), and defecation dysfunction (74%). Only 26 patients were asked about sexual dysfunction of whom 25 patients experienced dysfunction. Female gender was associated with more defecation dysfunction at presentation than male gender (OR 4.11; p = 0.039). All patients underwent decompressive surgery. Two post-operative follow-up (FU) moments took place after a mean of 75 h and 63 days. Outcomes at second FU moment: micturition dysfunction 48%, defecation dysfunction 42%, sexual dysfunction 53%, sciatica 48%, and altered sensation of the saddle area 57%. A shorter time to decompression was associated with more sciatica at FU 1 (p = 0.042) which effect had disappeared at FU 2. CONCLUSION: This study is unique in (1) displaying the presenting features in a large cohort of CES patients, (2) demonstrating that recovery after decompression is slow and far from complete in the majority of patients with regard to micturition, defecation, and sexual function and (3) evaluating predictors for outcome.

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

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.

Publication rate of paper and podium presentations from the European Section of the Cervical Spine Research Society Annual Meeting.

PURPOSE: The Cervical Spine Research Society Europe (CSRS-E) actively promotes scientific activities, the annual meeting being the most evident of them. The publication rate of oral and poster presentations at the annual meeting could be a measure for the success of the promotional activities. The publication rates of abstracts presented at the annual European meetings of the CSRS are unknown. The quality of the abstracts presented at a conference is reflected by the publication rate. A high publication rate is usually interpreted as representative of high scientific value of the conference. METHODS: Poster and podium presentations from the 2007 to 2012 annual meetings were identified. Pubmed was used to search for the abstract title and/or the combination of authors to verify whether the data were published in a peer-reviewed journal. Abstracts were considered published if the data presented at the meeting were identical to that in the publication. The journals in which the data were published were identified, as well as the origin of the research centre. RESULTS: From 2007 to 2012 826 abstracts were featured at the CSRS Europe annual meetings. There were 236 podium presentations and 590 poster presentations. 42 % of the podium presentations resulted in a publication, and 28 % of the poster presentations led to a publication. Overall, 32 % of accepted abstracts effectuated a publication in a peer-reviewed scientific journal. Abstracts from European research groups had a publication rate of 29 % compared to 34 % for abstracts from non-European research groups. Spine, European Spine Journal, Journal of Spinal Disorders and Techniques and J Neurosurgery Spine were the most common publication journals for the abstracts. The mean impact factor of the journals in which was published was 2.2. CONCLUSION: 42 % of the abstracts that were accepted for podium presentation at the CSRS Europe resulted in a publication in peer-reviewed MEDLINE indexed journals. Publication rates are at the high end of the publication rate spectrum of abstracts accepted for European scientific meetings.

Discussing sexual health in spinal care.

BACKGROUND: The possible detrimental effects of spinal disease on sexual health are widely recognized; however, it is not known to what extent neurosurgeons discuss this topic with their patients. The aim of this study is to identify knowledge, attitude and practice patterns of neurosurgeons counseling their patients about sexual health. METHODS: All members of the Dutch Association of Neurosurgery (neurosurgeons and residents) were sent a questionnaire addressing their attitudes, knowledge and practice patterns regarding discussing sexual health. RESULTS: Response rate was 62% with 89 questionnaires suitable for analysis. The majority of participants (83%) were male; mean age, 42.4 years. The mean experience in neurosurgical practice was 9 years. Respondents assumed that in 34% of their patients, sexual health was affected due to spinal disease. The majority of respondents (64%) stated that responsibility for discussing sexual health lies (partly) with the neurosurgeon; however, 73% indicated to (almost) never do this. The main reasons for not discussing sexual health were patients' old age (42%), lack of knowledge (38%) and lack of patients' initiative to bring up the subject (36%). Twenty-six percent indicated lack of time as a reason. There was no evidence for gender or doctor's age discordance as important barriers. Fifty percent of participants wished to gain more knowledge on discussing sexual health with patients. CONCLUSION: This study shows that despite high prevalence of sexual dysfunction (SD) in spinal patients, counseling about sexual health is not often done in neurosurgical care. More training on sexual health counseling early in the residency program seems critical. By initiating the discussion, clinicians who deal with spinal patients have the potential to detect sexual dysfunction (SD) and to refer adequately when necessary, thereby improving overall quality of life of their patients.

Complaints of micturition, defecation and sexual function in cauda equina syndrome due to lumbar disk herniation: a systematic review.

PURPOSE: Cauda equina syndrome (CES) is a rare complication of lumbar disk herniation. Although micturition, defecation and/or sexual function are by definition affected, little seems to be known about long-term outcome. Aim of this study is to review current literature on outcome of micturition, defecation and sexual function in CES due to lumbar disk herniation. METHODS: A literature search was done in Pubmed, Embase and Web of Science using a sensitive search string combination. Studies were selected by predefined selection criteria and risk of bias was assessed using a Cochrane checklist adjusted for this purpose. RESULTS: Fifteen studies were included. Risk of bias varied with six studies showing low risk. Mean minimal follow-up time was 17.0 months (range 3-24 months). All studies evaluated micturition and reported dysfunction at follow-up in 42.5% (range 13.3-90.0%). Defecation and sexual function were evaluated in eight and nine studies, respectively, and reported to be 49.6 (range 10.5-90.0%) and 44.3% (range 10.0-76.6%), respectively. Only two studies assessed sexual function in all patients at follow-up. CONCLUSION: This review offers an insight into the extent of micturition dysfunction, defecation dysfunction and sexual dysfunction (SD) in CES after decompression. Our findings show that dysfunction is extremely common, even at long-term follow-up. A condition as invalidating as CES requires proper patient information and the outcomes presented here may help in providing those data. Bias in included studies, lack of universal definitions and incomplete follow-up results qualify these data as the best we momentarily have, but still subject to improvement. Since SD seems to be severely underreported, we recommend further research to explore the extent of this problem, as well as the use of questionnaires in future clinical (prospective) studies to accomplish a more patient-based approach.

Pores in synthetic nerve conduits are beneficial to regeneration.

Current opinion holds that pores in synthetic nerve guides facilitate nerve regeneration. Solid factual support for this opinion, however, is absent; most of the relevant studies assessed only morphological parameters and results have been contradictory. To evaluate the effect of pores, the rat sciatic nerve was either autografted or grafted with nonporous, macroporous (10-230 mum), and microporous (1-10 microm) biodegradable epsilon-caprolactone grafts. Twelve weeks later, the grafted nerves were resected, and the electrophysiological properties were determined in vitro. Subsequently midgraft-level sections were inspected, and peroneal nerve sections were evaluated morphometrically. Finally, the gastrocnemic and tibial muscle morphometrical properties were quantified. The microporous nerve graft performed much better than the nonporous and macroporous grafts with respect to most parameters: it was bridged by a free floating bundle that contained myelinated nerve fibers, there were more nerve fibers present distal to the graft, the electrophysiological response rate was higher, and the decrease in muscle cross-sectional area was markedly smaller. Hence, the present study demonstrates the beneficial effect of synthetic nerve guide pores on nerve regeneration, although with the caveat that not pores per se, but only small (1-10 microm) pores were effective.

Type grouping in skeletal muscles after experimental reinnervation: another explanation.

Type grouping signifies clustering of muscle fibres of the same metabolic type, and is a frequent finding in reinnervated muscles. To elucidate the mechanism behind it, the rat sciatic nerve was either autografted or grafted with hollow synthetic nerve grafts. Twelve weeks later the number and fibre area of the type I and type II muscle fibres in the gastrocnemic and anterior tibial muscles were determined after ATP-ase staining. The number and diameter of peroneal nerve fibres distal to the grafts were measured, and the number of Aalpha-nerve fibres was derived. Nearly all nerve and muscle morphometrical parameters changed equally in both experimental groups. However, type grouping occurred frequently only after autografting, whereas the number of nerve fibres and the number of Aalpha-nerve fibres increased in this group. Hence type grouping cannot be explained by increased intramuscular sprouting subsequent to a decrease in the number of innervating nerve fibres, as previously presumed. Regenerating axons branch along their course through the peripheral nerve. We propose that the probability of the occurrence of type grouping is related to the dispersion of sibling branches in the nerve. In the autograft, emerging branches are kept together by Schwann cell basal lamina scaffolds, in contrast to the hollow synthetic nerve grafts where the emerging branches become dispersed. Thus, in muscles reinnervated after autografting, the probability that nerve branches that arrive at a specific muscle territory are sibling branches is greater than after hollow tube grafting. Consequently, the probability that type grouping will occur is greater.

Adhesion and proliferation of human Schwann cells on adhesive coatings.

Attachment to and proliferation on the substrate are deemed important considerations when Schwann cells (SCs) are to be seeded in synthetic nerve grafts. Attachment is a prerequisite for the SCs to survive and fast proliferation will yield large numbers of SCs in a short time, which appears promising for stimulation of peripheral nerve regeneration. The aim of the present study was to compare the adhesion and proliferation of human Schwann cells (HSCs) on different substrates. The following were selected for their suitability as an internal coating of synthetic nerve grafts; the extracellular matrix proteins fibronectin, laminin and collagen type I and the poly-electrolytes poly(d-lysine) (PDL) and poly(ethylene-imine) (PEI). On all coatings, attachment of HSCs was satisfactory and comparable, indicating that this factor is not a major consideration in choosing a suitable coating. Proliferation was best on fibronectin, laminin and PDL, and worst on collagen type I and PEI. Since nerve regeneration is enhanced by laminin and/or fibronectin, these are preferred as coatings for synthetic nerve grafts seeded with SCs.