Peripheral nerve graft architecture affects regeneration

The primary goal in repairing a peripheral nerve lesion is to guide the outgrowing axon back to its original target organ, which can be done by bridging the defect with an autograft or, more experimentally, a synthetic nerve graft. In this thesis an overview is presented of the evaluation methods that are currently used to assess peripheral nerve regeneration and their expediency is discussed. An in vitro electrophysiological evaluation method that charts the electrophysiological properties of the myelinated Aα- and Aβ-nerve fibres was introduced, and it was demonstrated that small differences between grafted nerves could be discriminated. Moreover, the electrophysiological data could be correlated to the morphometrical data, that was likewise broken up into Aα- and Aβ-components. This correlation especially provided new insight in the changes that occur in regenerating nerve fibres. After applying a panel of evaluation methods it was demonstrated that the presence of pores in and biodegradability of synthetic nerve grafts are beneficial to regeneration, evidenced mainly by preferable values of the electrophysiological parameters. Finally the changes that occurred in reinnervated muscles helped to gain insight into the preferential architecture of a synthetic nerve graft.​​​​​​​UBL - phd migration 201

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

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

Discussing sexual health in spinal care

Abstract 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. KEYWORDS: Cauda equina syndrome; Counseling; Patient care; Sexual dysfunction; Spinal cord injury GynecologyCervix cance

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

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

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( -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.\ud \ud 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

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