Bacterial growth in patients with low back pain and Modic changes: protocol of a multicentre, case-control biopsy study.

INTRODUCTION: Bacterial infection and Modic changes (MCs) as causes of low back pain (LBP) are debated. Results diverged between two randomised controlled trials examining the effect of amoxicillin with and without clavulanic acid versus placebo on patients with chronic LBP (cLBP) and MCs. Previous biopsy studies have been criticised with regard to methods, few patients and controls, and insufficient measures to minimise perioperative contamination. In this study, we minimise contamination risk, include a control group and optimise statistical power. The main aim is to compare bacterial growth between patients with and without MCs. METHODS AND ANALYSIS: This multicentre, case-control study examines disc and vertebral body biopsies of patients with cLBP. Cases have MCs at the level of tissue sampling, controls do not. Previously operated patients are included as a subgroup. Tissue is sampled before antibiotic prophylaxis with separate instruments. We will apply microbiological methods and histology on biopsies, and predefine criteria for significant bacterial growth, possible contamination and no growth. Microbiologists, surgeons and pathologist are blinded to allocation of case or control. Primary analysis assesses significant growth in MC1 versus controls and MC2 versus controls separately. Bacterial disc growth in previously operated patients, patients with large MCs and growth from the vertebral body in the fusion group are all considered exploratory analyses. ETHICS AND DISSEMINATION: The Regional Committees for Medical and Health Research Ethics in Norway (REC South East, reference number 2015/697) has approved the study. Study participation requires written informed consent. The study is registered at ClinicalTrials.gov (NCT03406624). Results will be disseminated in peer-reviewed journals, scientific conferences and patient fora. TRIAL REGISTRATION NUMBER: NCT03406624.

New contributions on chronic low back pain: disc infection or contaminated cultures?

There is controversy about the likely infectious origin of chronic low back pain, because it has been suggested the possibility of a relationship with infection by Cutibacterium acnes (C. acnes). The aim of this study is to compare four methods to determine the presence of a likely infection caused by C. acnes in surgical disc samples. This work is a cross-sectional observational study in which there are included 23 patients with microdiscectomy indication. Disc samples were taken during surgery and analysis was done by culture, Sanger sequencing, next-generation sequencing (NGS), and real-time PCR (qPCR). Furthermore, clinical data collection was conducted, and it was analyzed the presence of the Modic-like changes on the magnetic resonance imaging. In 5 of the samples from among the 23 patients (21.7%), C. acnes was isolated by culture. However, in none of the samples could its genome be detected through Sanger sequencing, the less sensitive method. Only the qPCR and NGS were able to detect very few copies of the genome of this microorganism in all the samples, with no significant quantitative differences being observed between the patients in whom isolation of the microorganism by culture was evident or not. Furthermore, there were no significant relationships identified between the clinical variables, including Modic alterations and positive cultures. The most sensitive methods to the detect C. acnes were NGS and qPCR. The data obtained do not suggest association between the presence of C. acnes and the clinical process and support the hypothesis that C. acnes is found in these samples only because it is a contamination from the skin microbiome.

When infection mimics cauda equina syndrome: a cautionary tale.

A 63-year-old man presented to the emergency department with low back pain, perineal and genital numbness, together with bilateral lower limb paraesthesia and urinary retention. He was admitted under the orthopaedic service for investigation of suspected cauda equina syndrome. Magnetic resonance imaging of his spine did not reveal any evidence of cauda equina compression. Magnetic resonance imaging of his brain demonstrated nonspecific multiple hyperintensities in the right frontotemporal and left temporo-occipital regions. Computed tomography of his chest, abdomen, and pelvis did not identify any evidence of malignancy. Cerebrospinal fluid from a lumbar puncture showed a high leucocyte count (predominantly lymphocytes). Viral cerebrospinal fluid polymerase chain reaction was positive for varicella zoster virus. A diagnosis of varicella zoster virus myeloradiculitis (Elsberg syndrome) was established and the patient was treated with intravenous aciclovir. Unfortunately, the patient succumbed to a devastating intracerebral haemorrhage during his inpatient stay, probably due to vasculopathy from the underlying varicella zoster virus infection. This case describes a rare infectious mimic of cauda equina syndrome. Elsberg syndrome is an infectious syndrome characterised by bilateral lumbosacral myeloradiculitis, with varicella zoster virus being a well-recognised aetiological agent. We discuss the relevant literature in detail and identify the key, cautionary lessons learned from this case.

A rare case of isolated cauda equina Nocardia farcinica infection.

Nocardia is a Gram-positive, partially acid-fast, catalase-positive, and urease-positive bacterium that grows aerobically. We present an extremely rare case of cauda equina syndrome due to isolated intramedullary Nocardia farcinica infection. A 44-year-old male presented with low backache and gradually progressive weakness in bilateral lower limbs followed by paraplegia. He was found to have a well-defined, sharply demarcated ring-enhancing lesion located from T11-T12 to L3 vertebral body. He underwent laminectomy and decompression. The histopathological examination revealed a Gram-positive filamentous organism that looks like Nocardia. The culture report was suggestive of Nocardia farcinica. He was then treated with antibiotics and had a remarkable clinical and radiological improvement.

A travel-loving woman in her eighties with lower back pain and weight loss. / En reiseglad 80-åring med ryggsmerter og vekttap.

BACKGROUND: This case report presents one of the first documented incidents of chronic Q-fever (C. burnetii) in Norway. A comprehensive workup resulted in an unexpected finding. CASE PRESENTATION: A Norwegian woman in her eighties presented to a district general hospital with lower back pain, decreased general condition and weight loss. Computer tomography (CT) revealed a large thoracic aortic aneurysm presumed to be of mycotic origin, and later magnetic resonance imaging (MRI) scans revealed osteomyelitis in the surrounding vertebrae. Conventional diagnostic workup did not identify the causative agent. After more than 6 months of different examinations, surgery, exhausting invasive procedures and antimicrobial treatment, we were ultimately successful in determining the microbial cause of chronic mycotic aneurism and osteomyelitis to be C. Burnetii (Q-fever) through serological and PCR analysis. INTERPRETATION: An increasing proportion of the population in all age groups travel abroad, and clinicians should be aware of the increasing incidence of imported infectious diseases. Obtaining a thorough medical history is still an important tool in the diagnostic process.

Is the discopathy associated with Modic changes an infectious process? Results from a prospective monocenter study.

BACKGROUND: The local infectious origin and the putative role of Cutibacterium acnes (CA) of a particular subtype of discopathy (Modic 1) are still debated. PURPOSE: To establish the association of CA in intervertebral disc (IVD) and Modic 1 discopathy in patients with low back pain. METHODS: The prevalence of bacteria in IVD samples obtained by anterior approach in patient with chronic low back pain harboring Modic type 1, 2 or no Modic changes was compared to that measured in IVD samples obtained by posterior approach for sciatica. From 45 patients included in the study, 77 discs samples were obtained: 58 by anterior approach (32 Modic 1/2 changes, 26 without Modic change) and 19 by posterior approach. Conventional microbial cultures, universal 16S rRNA molecular detection and a CA specific PCR were performed. RESULTS: 12 /77 (15.6%) disc samples were culture positive. Among the 10 CA positive cultures, 5 out of 58 (8.6%) were identified from specimens obtained by anterior approach and 5/19 (26.3%) from posterior approach (p = 0.046). Moreover, the percentage of CA culture positive sample was statistically no different between the patient with or without Modic changes. The CA prevalence was lower through molecular, culture-free approaches: the universal 16S rRNA PCR was positive for 6 specimens, including one CA positive sample and the CA specific PCR was positive for one specimen obtained by posterior approach. CONCLUSIONS: In spine surgery the prevalence of CA in culture was significantly higher in IVD samples collected through a posterior approach compared to an anterior approach, suggesting a contamination process. This study did not support the CA related local infectious origin of Modic 1 discopathy.

Epidural and Paraspinal Abscess Presenting as Acute Low Back Pain.

A 56-year-old man sought care from a primary care physician (PCP) 5 days after lifting a heavy box produced acute, isolated lumbar pain. The PCP diagnosed a lumbar disc herniation and referred the patient to physical therapy without diagnostic imaging. Due to the presence of multiple red flags leading up to and during examination, the patient was transferred to the emergency department for further evaluation. Magnetic resonance imaging revealed a spinal epidural abscess with an associated multiloculated abscess within the adjacent left paraspinal muscles. J Orthop Sports Phys Ther 2019;49(6):482. doi:10.2519/jospt.2019.8456.

Propionibacterium acnes induces discogenic low back pain via stimulating nucleus pulposus cells to secrete pro-algesic factor of IL-8/CINC-1 through TLR2-NF-κB p65 pathway.

Latent infection of Propionibacterium acnes was considered as a new pathogeny for low back pain (LBP); however, there is no credible animal evidence or mechanism hypothesis. This study proved that P. acnes is a causative pathogen of bacteria-induced LBP and investigated its underlying mechanism. For this, P. acnes was firstly identified in patients' degenerated intervertebral disc (IVDs) samples. The results of patients' Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Japanese Orthopaedic Association (JOA), and Oswestry Disability Index (ODI) scores indicated that P. acnes-positive patients showed more severe LBP and physical disability. Then, a P. acnes-inoculated lumbar IVDs model was established in rats. The results of paw/foot withdrawal threshold and qRT-PCR indicated that P. acnes-inoculated rats had obvious LBP in behavioral evaluation and over-expression of substance P (SP) and calcitonin gene-related peptide (CGRP) in IVDs. Subsequently, enzyme-linked immunosorbent assay (ELISA) results demonstrated that increased expression of IL-8 or CINC-1 (the homolog of IL-8 in rats) in the P. acnes-positive IVDs of human and rats. The CINC-1 injected animal model proved that the cytokines were able to induce LBP. Finally, the co-culture experiments showed that nucleus pulposus cells (NPCs) were able to respond to P. acnes and secreted IL-8/CINC-1 via TLR-2/NF-κB p65 pathway. In conclusion, P. acnes had strong association with LBP by stimulating NPCs to secrete pro-algesic factor of IL-8/CINC-1 via TLR2/NF-κBp65 pathway. The finding may provide a promising alternative therapy strategy for LBP in clinical. KEY MESSAGES: Patients with P. acnes-positive IVDs tended to have more severe LBP, physical disability, and increased IL-8 expressions. P. acnes can induce LBP via IL-8/CINC-1 in IVDs. P. acnes stimulate the NPCs to secrete pro-algesic factor of IL-8/CINC-1 via TLR2/NF-κBp65 pathway.

Importance of Propionibacterium acnes hemolytic activity in human intervertebral discs: A microbiological study.

Most patients with chronic lower back pain (CLBP) exhibit degenerative disc disease. Disc specimens obtained during initial therapeutic discectomies are often infected/colonized with Propionibacterium acnes, a Gram-positive commensal of the human skin. Although pain associated with infection is typically ascribed to the body's inflammatory response, the Gram-positive bacterium Staphylococcus aureus was recently observed to directly activate nociceptors by secreting pore-forming α-hemolysins that disrupt neuronal cell membranes. The hemolytic activity of P. acnes in cultured disc specimens obtained during routine therapeutic discectomies was assessed through incubation on sheep-blood agar. The ß-hemolysis pattern displayed by P. acnes on sheep-blood agar was variable and phylogroup-dependent. Their molecular phylogroups were correlated with their hemolytic patterns. Our findings raise the possibility that pore-forming proteins contribute to the pathogenesis and/or symptomology of chronic P. acnes disc infections and CLBP, at least in a subset of cases.

[Psoas abscess due to Candida tropicalis: a case report]. / Abcès de psoas à Candida tropicalis : à propos d'un cas.

Psoas abscess is a rare infection, difficult to diagnose, which can be primary or secondary, it is often caused by a bacterial micro-organism (Staphylococcus aureus, Escherichia coli), and in rare cases by a fungal micro-organism (Candida). We report an exceptional case of Candida tropicalis psoas abscess in a 52-year-old man with no history of pathology who had inflammatory lower back pain with fever and general deterioration. The biological assessment showed a renal insufficiency and a biological inflammatory syndrome, a computed tomography made in urgency was in favor of a psoas abscess. The bacteriological study of percutaneous drainage product allowed to isolate Candida tropicalis.

Fungal Lumbosacral Osteomyelitis After Robotic-Assisted Laparoscopic Sacrocolpopexy.

Sacral osteomyelitis is a rare complication after robotic sacrocolpopexy, with previous reports of enteric and skin flora as inciting organisms. We report a patient who presented with severe low back pain and fever 6 weeks after a robotic sacrocolpopexy, who was subsequently diagnosed as having lumbosacral discitis and osteomyelitis with thoracic intervertebral extension. Empiric antibiotic therapy was initially administered. After laparoscopic mesh excision and abdominal wash out, Candida albicans was isolated from the excised mesh. Postoperatively, the patient was treated with a 12-month course of oral fluconazole with significant clinical improvement. To our knowledge, this is the second reported case of fungal osteomyelitis, providing further recommendations for the management of postoperative sacral osteomyelitis using a minimally invasive surgical technique and guidance by a multidisciplinary team.

Vertebral Osteomyelitis Caused by Helicobacter cinaedi Identified Using Broad-range Polymerase Chain Reaction with Sequencing of the Biopsied Specimen.

A 65-year-old man presented with gradually exacerbating low back pain. Magnetic resonance imaging revealed vertebral osteomyelitis in the Th11-L2 vertebral bodies and discs. The patient showed negative findings on conventional cultures. Direct broad-range polymerase chain reaction (PCR) with sequencing of the biopsied specimen had the highest similarity to the 16S rRNA gene of Helicobacter cinaedi. This case suggests that direct broad-range PCR with sequencing should be considered when conventional cultures cannot identify the causative organism of vertebral osteomyelitis, and that this method may be particularly useful when the pathogen is a fastidious organism, such as H. cinaedi.

Subclinical Propionibacterium acnes infection estimation in the intervertebral disc (SPInE-ID): protocol for a prospective cohort.

INTRODUCTION: Low back pain and vertebral endplate abnormalities are common conditions within the population. Subclinical infection caused by indolent pathogens can potentially lead to these findings, with differentiation between them notably challenging from a clinical perspective. Progressive infection of the intervertebral disc has been extensively associated with increasing low back pain, with Propionibacterium acnes specifically implicated with in relation to sciatica. The main purpose of this study is to identify if the presence of an infective pathogen within the intervertebral disc is primary or is a result of intraoperative contamination, and whether this correlates to low back pain. METHODS AND ANALYSIS: An open prospective cohort study will be performed. Subjects included within the study will be between the ages of 18 and 65 years and have a diagnosis of lumbar disc herniation requiring open decompression surgery. Excised herniated disc fragments, muscle and ligamentum flavum samples will be collected during surgery and sent to microbiology for tissue culture and pathogen identification. Score questionnaires for pain, functionality and quality of life will be given preoperatively and at 1, 3, 6 and 12 months postoperatively. A MRI will be performed 12 months after surgery for analysis of Modic changes and baseline comparison. The primary endpoint is the rate of disc infection in patients with symptomatic degenerative disc disease. The secondary endpoints will be performance scores, Modic incidence and volume. ETHICS AND DISSEMINATION: This study was approved by our Institutional Review Board and was only initiated after it (CAAE 65102617.2.0000.0071). Patients agreeing to participate will sign an informed consent form before entering the study. Results will be published in a peer reviewed medical journal irrespective of study findings. If shown to be the case, this would have profound effects on the way physicians treat chronic low back pain, even impacting health costs. TRIALS REGISTRATION NUMBER: NCT0315876; Pre-results.

Multilevel lumbar spine infection due to poor dentition in an immunocompetent adult: a case report.

BACKGROUND: Although spinal infections have been reported following dental procedures, development of a spinal infection attributed to poor dentition without a history of a dental procedure in an immunocompetent adult has not been previously reported. Here we provide a case report of a multilevel lumbar spine infection that developed in an immunocompetent adult with poor dentition. CASE PRESENTATION: A 63-year-old white male man with past medical history of hypertension presented to a hospital emergency department with a 4-month history of progressively worsening low back pain. A musculoskeletal examination demonstrated diffuse tenderness in his lumbar spine area and the results of a neurological examination were within normal limits. Computed tomography and magnetic resonance imaging of his lumbar spine demonstrated a prevertebral and presacral fluid collection ventral to the L4 to L5 and L5 to S1 interspaces. Blood cultures grew pan-sensitive Streptococcus intermedius in four of four bottles within 45 hours. Using computed tomography guidance, three core biopsies of the L4 to L5 interspace were taken and subsequent cultures were positive for Streptococcus intermedius. He reported that his last episode of dental care occurred more than 20 years ago and a dental panoramic radiograph demonstrated significant necrotic dentition. Ten teeth were extracted and the necrotic dentition was assumed to be the most likely source of infection. On hospital dismissal, he received a 12-week course of intravenously administered ceftriaxone followed by an 8-week course of orally administered cefadroxil pending repeat imaging. CONCLUSIONS: This case report demonstrates the importance of determining the source of infection in a patient with a spontaneous spinal infection. Even in the absence of a recent dental procedure, dentition should be considered a possible source of infection in an immunocompetent patient who presents with a spontaneous spinal infection.

What Is the Role of the Bacterium Propionibacterium acnes in Type 1 Modic Changes? A Review of the Literature.

This review presents a summary of the pathology and epidemiology of Modic changes and the possible role of Propionibacterium acnes. This information is followed by a synthesis of the most recent clinical research involved in culturing the discs of patients with degenerative disc disease for the presence of bacteria. We also discuss a randomized controlled trial that investigates the effects of antibiotics on patients with chronic low back pain and type 1 Modic changes. We conclude with a brief discussion of the difficulties involved in this research and the significance of the findings.

Cervical facet joint septic arthritis: a real pain in the neck.

A 64-year-old man with a complex medical history and previous cervical arthritis with discectomy presents with a 2-day history of neck and lower back pain and shortness of breath, associated with left-sided muscle weakness. He has a fever with severe sepsis causing acute renal failure. MRI spine shows evidence of left cervical facet joint septic arthritis at C6-T1. He required 6 weeks of intravenous antibiotics and intensive support with ventilation and haemofiltration. After completion of antibiotics, he made a full recovery and regained neurological function before discharge.

Histological Identification of Propionibacterium acnes in Nonpyogenic Degenerated Intervertebral Discs.

Purpose. Low-virulence anaerobic bacteria, especially the Propionibacterium acnes (P. acnes), have been thought to be a new pathogeny for a series of disc diseases. However, until now, there has been no histological evidence to confirm this link. The purpose of this study was to confirm the presence of P. acnes in nonpyogenic intervertebral discs via histological observation. Method. Degenerated intervertebral discs were harvested from 76 patients with low back pain and/or sciatica but without any symptoms of discitis or spondylodiscitis. The samples were cultured under anaerobic conditions and then examined using 16S rDNA PCR to screen for P. acnes. Samples found to be positive for P. acnes were stained with hematoxylin-eosin (HE) and modified Brown-Brenn staining and observed under a microscope. Results. Here, 16 intervertebral discs were found to be positive for P. acnes via 16S rDNA PCR and the prevalence was 21.05% (16/76). Among them, 7 samples had visible microbes stained with HE and modified Brown-Brenn staining. Morphological examination showed the bacteria to be Gram-positive and rod-shaped, so they were considered P. acnes. Conclusion. P. acnes is capable of colonizing some degenerated intervertebral discs without causing discitis, and its presence could be further confirmed by histological evidence. Targeting these bacteria may be a promising therapy method for some disc diseases.

Propionibacterium acnes Incubation in the Discs Can Result in Time-Dependent Modic Changes: A Long-Term Rabbit Model.

STUDY DESIGN: A case-control study of animal model of Modic changes (MCs) on rabbits. OBJECTIVE: To evaluate the feasibility of inducing of MCs by injection of Propionibacterium acne (P. acnes) into the lumbar intervertebral discs of rabbits. SUMMARY OF BACKGROUND DATA: MCs have been widely observed, and assume to be closely associated with low back pain and P. acnes, but there are few animal models showing the progression of MCs. METHODS: Ten rabbits were used for the study. The L3-4 and L4-5 discs of all rabbits were injected with 100 µL P. acnes (1.6 × 10 CFU/mL) as P. acnes group, L2-3 disc were injected with 100 µL normal saline as vehicle, and L5-6 disc was untreated (blank). MCs were investigated by magnetic resonance imaging before operation and at 2 weeks, 1, 3, 4.5, 6, and 9 months postoperatively. Following sacrifice, histological analysis, blood test and micro-computed tomography were performed. Cytokine expression in nucleus and endplate tissues was quantified using real-time polymerase chain reaction. RESULTS: From 3 months postoperatively, the P. acnes group showed significantly decreased T1-weighted signal intensity, whereas the T2-weighted signal was significantly higher at 3 and 4.5 months, and then decreased remarkably at 6 and 9 months. Eleven of 20 inferior endplates were identified as type I MCs at 4.5 months, and 9 of 20 were identified as type II MCs at 9 months. Real-time polymerase chain reaction showed that expression of interleukin-1ß, tumor necrosis factor α, interferon-γ, matrix metalloproteinase-9, and thrombospondin motifs-5 in the nucleus pulposus, and interleukin-1ß, tumor necrosis factor α, and thrombospondin motifs-5 in the endplates, were significantly upregulated after injection of P. acnes. Histological slices of discs injected with P. acnes showed disc degeneration, endplate abnormalities, and inflammatory response, with micro-computed tomography confirming bone resorption. CONCLUSION: P. acnes infection of the disc can induce degeneration of the disc and an inflammatory response in the endplate region, presenting as MCs type I and II time dependently. LEVEL OF EVIDENCE: N/A.

The Influence of Direct Inoculation of Propionibacterium acnes on Modic Changes in the Spine: Evidence from a Rabbit Model.

BACKGROUND: Modic changes (inflammatory-like changes visible on magnetic resonance imaging [MRI] scans of a vertebral end plate) are common and are associated with low back pain, but their origin is unclear. To our knowledge, there have been no previous in vivo animal models of Modic changes. We hypothesized that Modic changes may be related to Propionibacterium acnes. METHODS: Ten New Zealand White rabbits were injected percutaneously with 1 mL of P. acnes (1.6 × 10 colony forming units/mL) into the subchondral bone superior to the L4-L5 and L5-L6 discs; 10 other control rabbits received sham injections at L4-L5 and 1 mL of normal saline solution (vehicle) at L5-L6. The subchondral bone superior to L3-L4 discs was untreated (blank). Development of Modic changes was investigated with MRI studies before the operation and at 2 weeks and 1, 2, 3, and 6 months postoperatively. Following sacrifice of the rabbits, histological analysis and microcomputed tomography (micro-CT) were performed, and blood samples were analyzed. Cytokine expression in end-plate tissues was quantified using real-time polymerase chain reaction (PCR). RESULTS: The group that received P. acnes showed significantly increased T1-weighted signal intensity at 6 months (mean and standard deviation, 3.43 ± 0.41 [range, 2.42 to 4.44] compared with 2.43 ± 0.66 [range, 1.98 to 2.87] before the injection) and higher T2-weighted signal intensity at 6 months. Positive culture results were obtained from 9 of 20 samples injected with P. acnes. Specimens with positive cultures had a higher prevalence of Modic changes (4 of 9 samples positive for P. acnes compared with 3 of 11 samples negative for P. acnes). Real-time PCR showed significantly increased expression of tumor necrosis factor-α, interleukin-1ß, and interferon-γ following injection of P. acnes, but no changes were seen on histological analysis, micro-CT, or blood analysis. CONCLUSIONS: P. acnes can survive within the end-plate region and can initiate mild inflammatory-like responses from host cells, leading to signal intensity changes in MRI scans, which potentially resemble Modic changes. CLINICAL RELEVANCE: Disc degeneration and low back pain are associated with Modic changes. Our results indicate that Modic changes can be associated with P. acnes in the conjunction area of the disc and subchondral bone. These results may be useful for understanding the underlying mechanisms of Modic changes and related pain.