Purpose The aim of this observational radiographic and proteomic study is to explore the influence of both Modic change (MC) and endplate avulsion (EPA) on the inflammation profile of herniated... Show morePurpose The aim of this observational radiographic and proteomic study is to explore the influence of both Modic change (MC) and endplate avulsion (EPA) on the inflammation profile of herniated discs using a proteomic and bioinformatics approach. Methods Fifteen nucleus pulposus (NP) harvested from surgery underwent LC-MS/MC analysis, the proteome was subsequently scanned for inflammatory pathways using a bioinformatics approach. All proteins that were identified in inflammatory pathways and Gene Ontology and present in > 7 samples were integrated in a multiple regression analysis with MC and EPA as predictors. Significant proteins were imputed in an interaction and pathway analysis. Results Compared to annulus fibrosus tear (AFT), six proteins were significantly altered in EPA: catalase, Fibrinogen beta chain, protein disulfide-isomerase, pigment epithelium-derived factor, osteoprotegerin and lower expression of antithrombin-III, all of which corresponded to an upregulation of pathways involved in coagulation and detoxification of reactive oxygen species (ROS). Moreover, the presence of MC resulted in a significant alteration of nine proteins compared to patients without MC. Patients with MC showed a significantly higher expression of clusterin and lumican, and lower expression of catalase, complement factor B, Fibrinogen beta chain, protein disulfide-isomerase, periostin, Alpha-1-antitrypsin and pigment epithelium-derived factor. Together these altered protein expressions resulted in a downregulation of pathways involved in detoxification of ROS, complement system and immune system. Results were verified by Immunohistochemistry with CD68 cell counts. Conclusion Both EPA and MC status significantly influence disc inflammation. The beneficial inflammatory signature of EPA illustrates that endplate pathology does not necessarily have to worsen the outcome, but the pathological inflammatory state is dependent on the presence of MC. Show less
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... Show moreBackground: 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. Show less
The frequently diagnosed lumbar disc herniation can disappear by natural course, but still leads to high low back surgery rates. The optimal period of conservative care, before surgery is executed,... Show moreThe frequently diagnosed lumbar disc herniation can disappear by natural course, but still leads to high low back surgery rates. The optimal period of conservative care, before surgery is executed, was unknown. It is surprising that scientific evidence was lacking which justified “early” surgery. Surgery, after 6-12 weeks of sciatica, was compared to prolonged conservative care in 283 patients in a randomized study. Primary outcomes were perceived recovery, leg pain intensity and functioning. Early surgery resulted in a 2 times faster recovery rate, compared to prolonged conservative care. From the latter group 39 percent of patients could not evade surgery. Within one year, however, both groups presented similar recovery rates and outcome. The impossibility to sit, because of sciatica, seemed to be a good argument to decide for early surgery. Intense pain and disability were predictors for delayed surgery. Compared to men, females exhibited a 3 times higher odds to develop chronic pain. The higher medical costs of early surgery were fully compensated by quick resumption of working capacity. From a medical point of view one may favor a prolonged wait-and-see strategy but our western society urges patients to decide for early surgery to resume daily activities. Show less
