Voluntary running attenuates behavioural signs of low back pain: dimorphic regulation of intervertebral disc inflammation in male and female SPARC-null mice.

OBJECTIVE: To examine the effect of running exercise on behavioral measures of pain and intervertebral disc (IVD) inflammation in the SPARC-null mouse model. METHODS: Male and female 8-month old SPARC-null and age-matched control mice received a home cage running wheel or a control, fixed wheel for 6 months. Behavioral assays were performed to assess axial discomfort (grip test) and radiating leg pain (von Frey, acetone tests) and voluntary running was confirmed. Expression of inflammatory mediators (TNF-α, IL-1ß, IL-2, IL-10, CCL5, CXCL1, CXCL5, RANKL, M-CSF, and VEGF) in IVDs was determined. Additional inflammatory (IL-1ß, IL-1Ra, CXCR1, CXCR2) and macrophage phenotypic markers (ITGAM, CD80, CD86, CD206, Arg1) in IVDs were investigated by qPCR. RESULTS: Voluntary running attenuated behavioral measures of pain in male and female SPARC-null mice. Increases in mediators including IL-1ß, CXCL1 and CXCL5 were observed in SPARC-null compared to control IVDs. After 6 months of running, increases in M-CSF and VEGF were observed in male SPARC-null IVDs. In females, pro-inflammatory mediators, including CXCL1 and CXCL5 were downregulated by running in SPARC-null mice. qPCR analysis further confirmed the anti-inflammatory effect of running in female IVDs with increased IL-1Ra mRNA. Running induced upregulation of the macrophage marker ITGAM mRNA in males. CONCLUSIONS: Voluntary running reversed behavioral signs of pain in male and female mice and reduced inflammatory mediators in females, but not males. Thus, the therapeutic mechanism of action may be sex-specific.

One-stage posterior debridement, autogenous spinous process bone graft and instrumentation for single segment lumbar pyogenic spondylitis.

To compare the surgical outcomes of autogenous spinous process with iliac bone graft in managing single segment lumbar pyogenic spondylitis (PS) after posterior debridement and instrumentation. We performed a retrospective study for adult patients with single level lumbar PS. 60 patients with single segment lumbar PS underwent one-stage posterior debridement, autogenous bone graft and instrumentations. The patients were divided into Group A (autogenous iliac bone) and Group B (autogenous spinous process). Preoperative Charlson comorbidity index (CCI) was analyzed to assess the comorbidity. Low back pain was evaluated using the visual analog scale (VAS). Neurological status was assessed with the American Spinal Injury Association (ASIA) scale. Clinical infection index including the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) was also reviewed. Moreover, fusion and changes of sagittal alignment were investigated radiologically. There was a significantly longer operative time, hospital stay and greater blood loss in group A. The VAS scores improved significantly at each follow-up interval and post-operative VAS score was significantly lower in group B. At the last follow-up, ESR and CRP returned to normal for all patients. There was at least one grade level improvement in ASIA score. No statistical difference in corrected rate, loss of sagittal angle and lumbar lordosis was found between the two groups. There was no significant difference in fusion rate, mean fusion time and complications between the two groups. Compared with iliac bone graft, the autogenous spinous process bone graft can be less invasive and painful for the single segment lumbar PS. One-stage posterior debridement, autogenous spinous process bone graft and instrumentation can provide satisfactory results for appropriate cases.

Effect of adalimumab on axial manifestations in Japanese patients with psoriatic arthritis: a 24 week prospective, observational study.

OBJECTIVES: PsA is characterized by enthesitis, synovitis and osseous involvement in the peripheral and axial joints. Few studies have examined axial involvement in PsA using imaging techniques. Here we examined axial involvement in PsA patients using MRI. In addition, we determined the efficacy of 24 week adalimumab treatment in improving the MRI findings of spondylitis and sacroiliitis. METHODS: This was a prospective, open-label, single-arm study in patients with PsA. Adalimumab was administered to patients for a total of 24 weeks. MRI examinations were conducted at baseline and at week 24 of adalimumab treatment. RESULTS: Thirty-seven patients with PsA were included in this study. Spondylitis was observed in at least one site of the positive scan in 91% (n = 31) of patients with PsA. The number of arthritic sites in the cervical, thoracic and lumbar regions of the spine was 48, 67 and 53, respectively. All patients had MRI-determined sacroiliitis of grade ≥1 severity while 28 patients (82%) had grade ≥2 sacroiliitis in at least one sacroiliac region. Sacroiliac arthritis was statistically more severe on the right side than on the left side (P < 0.05). In 34 patients with PsA, the thoracic spine was the most common site of spondylitis. In addition, 24 week adalimumab treatment led to an improvement in the mean number of spondylitis sites and the mean grade of sacroiliitis. CONCLUSION: Treatment with adalimumab for 24 weeks resulted in improvement in spondylitis and sacroiliitis.

The peculiarities and treatment outcomes of the spinal form of chronic non-bacterial osteomyelitis in children: a retrospective cohort study.

Chronic non-bacterial osteomyelitis (CNO) is a group of immune-mediated diseases which appears in bone inflammation, destruction and some orthopaedic consequences, especially in the cases of spinal involvement. This study is to compare characteristics and treatment outcomes of CNO patients with spinal involvement. The retrospective cohort study included data from 91 pediatric patients with CNO. The diagnosis is based on Jannson's criteria with morphological confirmation (nonspecific chronic inflammation). Spine involvement detected by X-ray, computed tomography, magnetic resonance imaging, and bone scan in 29 (31.9%) patients. No differences in the family history, concomitant immune-mediated diseases between spinal (SpCNO) and peripheral (pCNO) forms of CNO have been revealed. Only 5 (10.2%) SpCNO patients (10.2%) had monofocal monovertebral involvement. The main risk factors of spinal involvement were female sex: RR = 2.0 (1.1; 3.9), sensitivity (Se) = 0.66, specificity (Sp) = 0.6; multifocal involvement: RR = 2.1 (0.9; 5.0), Se = 0.83, Sp = 0.37; no foot bones involvement: RR = 3.1 (1.3; 7.5), Se = 0.83, Sp = 0.5; sternum involvement RR = 2.3 (1.3; 4.1), Se = 0.24, Sp = 0.94. In the linear regression analysis only female sex (p = 0.005), multifocal involvement (p = 0.000001) and absence of foot bones involvement (p = 0.000001) were independent risk factors of spinal involvement (p = 0.000001). The response rate on bisphosphonates and tumor necrosis factor-a inhibitors was 90.9% and 66.7%, consequently. Only 4/29 (13.8%) SpCNO patients underwent surgery due to severe spinal instability or deformities. The spinal involvement is frequent in CNO and could be crucial for choosing a treatment strategy. Bisphosphonates and TNFa-inhibitors could be effective treatment options for severe SpCNO.

Granulomatous infective spondylitis in a patient presenting with progressive difficulty in walking: the differential between tuberculosis and brucellosis.

We report a case of infectious spondylitis in a 52-year-old woman who presented with progressive difficulty in walking. The patient had a 2-month long history of neurological symptoms, which progressed rapidly to paraplegia, following her admission. Imaging studies demonstrated the presence of vertebral lesions as well as additional tissue with inflammatory elements in the spinal canal, which caused a mass effect. In combination with the presence of increased cells and protein in the cerebrospinal fluid (CSF), the differential was steered towards causes of infectious spondylitis, primarily tuberculosis. However, brucellosis was also considered, as it is endemic in our area. Prompt surgical decompression produced biopsy samples, which confirmed the presence of granulomatous inflammation. The patient was started on an empiric regimen covering both for tuberculosis and brucellosis, and gradually regained full mobility in her lower limbs. The differential of infectious spondylitis is discussed, with an emphasis on the differentiation between tuberculosis and brucellosis.

Spinal Infections Among Patients With Long-Term Central Venous Catheters for Home Parenteral Nutrition.

Spinal infections are a rare yet serious metastatic complication of bacteremia among patients with long-term central venous catheters (CVCs) for which clinicians must remain vigilant. We performed a retrospective review of all cases of spinal infection occurring in the context of a CVC for long-term parenteral nutrition (PN) managed in our department between January 2010 and October 2013, a cohort of 310 patients over this time period. Six patients were identified (mean age, 65 years; 5 male). One hundred percent of patients presented with spinal pain (5/6 cervical, 1/6 thoracic). Organisms were cultured from the CVC in 5 of 6 patients. In all cases, the white blood cell count was normal, and in 5 of 6, C-reactive protein was normal. All diagnoses were confirmed on magnetic resonance imaging (MRI), and in 3 of 6 cases, an MRI was repeated (on the advice of neurosurgical colleagues) to confirm resolution of changes after a period of antimicrobial therapy. There was no clear correlation between duration of PN or number of days following CVC insertion and onset of infection. The CVC was replaced in 4 of 6 patients at the time of diagnosis, delayed removal in 1 of 6, and salvaged in the remaining case. Although rare, a high index of suspicion is needed in patients receiving long-term PN who present with spinal pain. Peripheral inflammatory markers may not be elevated. MRI should be performed and patients should be treated with antibiotics alongside involvement of local microbiology and neurosurgical teams. Multidisciplinary discussion on CVC salvage in these cases is important, especially in cases of challenging vascular anatomy.

Whole-body Vibration at Thoracic Resonance Induces Sustained Pain and Widespread Cervical Neuroinflammation in the Rat.

BACKGROUND: Whole-body vibration (WBV) is associated with back and neck pain in military personnel and civilians. However, the role of vibration frequency and the physiological mechanisms involved in pain symptoms are unknown. QUESTIONS/PURPOSES: This study asked the following questions: (1) What is the resonance frequency of the rat spine for WBV along the spinal axis, and how does frequency of WBV alter the extent of spinal compression/extension? (2) Does a single WBV exposure at resonance induce pain that is sustained? (3) Does WBV at resonance alter the protein kinase C epsilon (PKCε) response in the dorsal root ganglia (DRG)? (4) Does WBV at resonance alter expression of calcitonin gene-related peptide (CGRP) in the spinal dorsal horn? (5) Does WBV at resonance alter the spinal neuroimmune responses that regulate pain? METHODS: Resonance of the rat (410 ± 34 g, n = 9) was measured by imposing WBV at frequencies from 3 to 15 Hz. Separate groups (317 ± 20 g, n = 10/treatment) underwent WBV at resonance (8 Hz) or at a nonresonant frequency (15 Hz). Behavioral sensitivity was assessed throughout to measure pain, and PKCε in the DRG was quantified as well as spinal CGRP, glial activation, and cytokine levels at Day 14. RESULTS: Accelerometer-based thoracic transmissibility peaks at 8 Hz (1.86 ± 0.19) and 9 Hz (1.95 ± 0.19, mean difference [MD] 0.290 ± 0.266, p < 0.03), whereas the video-based thoracic transmissibility peaks at 8 Hz (1.90 ± 0.27), 9 Hz (2.07 ± 0.20), and 10 Hz (1.80 ± 0.25, MD 0.359 ± 0.284, p < 0.01). WBV at 8 Hz produces more cervical extension (0.745 ± 0.582 mm, MD 0.242 ± 0.214, p < 0.03) and compression (0.870 ± 0.676 mm, MD 0.326 ± 0.261, p < 0.02) than 15 Hz (extension, 0.503 ± 0.279 mm; compression, 0.544 ± 0.400 mm). Pain is longer lasting (through Day 14) and more robust (p < 0.01) after WBV at the resonant frequency (8 Hz) compared with 15 Hz WBV. PKCε in the nociceptors of the DRG increases according to the severity of WBV with greatest increases after 8 Hz WBV (p < 0.03). However, spinal CGRP, cytokines, and glial activation are only evident after painful WBV at resonance. CONCLUSIONS: WBV at resonance produces long-lasting pain and widespread activation of a host of nociceptive and neuroimmune responses as compared with WBV at a nonresonance condition. Based on this work, future investigations into the temporal and regional neuroimmune response to resonant WBV in both genders would be useful. CLINICAL RELEVANCE: Although WBV is a major issue affecting the military population, there is little insight about its mechanisms of injury and pain. The neuroimmune responses produced by WBV are similar to other pain states, suggesting that pain from WBV may be mediated by similar mechanisms as other neuropathic pain conditions. This mechanistic insight suggests WBV-induced injury and pain may be tempered by antiinflammatory intervention.

Age-related inflammatory changes in the spine as demonstrated by (18)F-FDG-PET:observation and insight into degenerative spinal changes.

Our aim was to determine whether the inflammatory component associated with age-related degenerative changes in the spine can be assessed by (18)F-fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET). Mean and maximum standardize uptake values (SUV(mean) and SUV(max)) of intervertebral discs and spinous processes were measured in 45 patients who had undergone (18)F-FDG-PET for any clinical indication. Correlations between age and FDG-PET indices (SUV(mean) and SUV(max) of intervertebral discs and spinous processes) were determined. Pearson's correlation coefficients between age and intervertebral disc SUV(mean), between age and intervertebral disc SUV(max), and between age and spinous process SUV(mean) were 0.4821, 0.3946, and 0.5017 (P<0.05), indicating moderate positive correlations between these parameters. However, Pearson's correlation coefficient between age and spinous process SUV(max)was 0.7998 (P>0.05), indicating no correlation between these two parameters. In conclusion, intensity of (18)F-FDG uptake in the intervertebral discs and spinous processes generally increases with aging, which is likely to reflect associated inflammatory processes.

Pyogenic spondylitis.

Pyogenic spondylitis is a neurological and life threatening condition. It encompasses a broad range of clinical entities, including pyogenic spondylodiscitis, septic discitis, vertebral osteomyelitis, and epidural abscess. The incidence though low appears to be on the rise. The diagnosis is based on clinical, radiological, blood and tissue cultures and histopathological findings. Most of the cases can be treated non-operatively. Surgical treatment is required in 10-20% of patients. Anterior decompression, debridement and fusion are generally recommended and instrumentation is acceptable after good surgical debridement with postoperative antibiotic cover.

The effectiveness of a biologic agent on axial manifestations of psoriatic arthritis. A twelve months observational study in a group of patients treated with etanercept.

OBJECTIVES: To investigate the effectiveness of etanercept on axial manifestations of a group of patients with established psoriatic arthritis (PsA). METHODS: This was a multicentre observational study. PsA was classified based on the CASPAR criteria. Inclusion criteria were refractory PsA with axial manifestations and suitability for anti TNF-α therapy. Effectiveness was defined according to the ASAS response criteria (BASDAI: 50% relative or absolute change of 20mm and expert opinion in favour of continuation), and on the improvements of BASFI, anthropometric measures, PASI, ESR and CRP at 12 months. PASI 50 and 75 were also assessed, as well as the ACR20 and ACR50 response criteria for patients with peripheral arthritis. Comparisons between baseline and after 12-month treatment were done using the Wilcoxon signed rank test for the end-points considered. RESULTS: The study included 32 patients (25/7 M/F; median age 51yrs; 25th-75th percentiles: 34.5-58.7; median disease duration 14.5 yrs; 25th-75th percentiles: 9.2-17.00). Effectiveness of etanercept was observed in 72% of patients for the BASDAI (p<0.001), in 68% for the BASFI (p<0.001), in 76% for ESR (p<0.001) and in 68% of patients for CRP (p<0.01). The PASI improved in 72% of patients treated (p<0.0001), while PASI 50 and PASI 75 was reached in 81% and 55% of patients, respectively. ACR 20 and 50 was reached in 78 and 56% of patients with peripheral involvement respectively. CONCLUSIONS: The present study has shown that etanercept is effective on axial manifestations of established PsA, confirming the positive effects of anti TNF-α therapy on clinical manifestations of the disease.

Rheumatologic manifestations of brucellosis.

Brucellosis, an endemic disease in certain parts of the world is usually accompanied by osteoarticular involvement. The present study was performed to determine the types and frequency of rheumatologic manifestations in patients with brucellosis diagnosed in the north of Iran. Diagnosis of active brucellosis was based on the serological tests along with compatible clinical findings. Musculoskeletal involvement of brucellosis was confirmed by clinical and radiographic examinations; 51 (32 males, 19 females) patients with mean (SD) age of 35 (19) years old were studied. Rheumatological manifestations were observed in 94% of patients. The most frequent skeletal findings in order of frequency were peripheral arthritis, sacroiliitis; and spondylitis which occurred in 37; 31 and 8% of patients, respectively. Back pain, arthralgia, myalgia, and enthesopathy were also reported in 49, 34, 11.7% of patients, respectively. Based on the findings of this study, rheumatologic manifestations are common in brucellosis; therefore, in the endemic areas, brucellosis should be considered in the differential diagnosis of patients who present with any type of rheumatologic manifestations.

Role of magnetic resonance imaging in evaluation of tubercular spondylitis: pattern of disease in 100 patients with review of literature.

INTRODUCTION: The purpose of this study is to evaluate the role of magnetic resonance imaging (MRI) in evaluation of tubercular spondylitis and to correlate imaging findings with clinical severity of the disease. METHODS: One hundred consecutive patients, who presented with features suggestive of spinal infections, were subjected to MRI examination. T1W and STIR images were obtained followed by T2W and post-contrast T1W images. Various imaging characteristics of spinal infections were noted and correlated with the clinical severity of the disease. RESULTS: Backache was the most common presenting symptom present in 86 %, while paraparesis was the most common sign seen in 62 %. The neurological status of the patients correlated well with MRI findings in the majority of the cases with an overall good correlation obtained in 96 % of cases. The majority of the vertebrae and intervertebral discs affected showed hypointensity or isointensity on T1W images and hyperintensity on T2W images. Epidural/dural disease was present in 74 % while 68 % of patients demonstrated decreased intervertebral disc height. Epidural extension and subligamentous spread was in 74 % and 90 % of patients respectively. CONCLUSIONS: MRI plays a vital role in early and accurate diagnosis of spinal infections. It is non-invasive and clearly demonstrates soft tissue anatomy and pathology which makes it superior to X-rays and Computed Tomography (CT). Imaging findings of tubercular spondylitis were also found to have a good correlation with the clinical status of the patients. Hence, it is of much help in the evaluation and assessment of patients presenting with features of spinal infections.

Co-occurrence of outlet impingement syndrome of the shoulder and restricted range of motion in the thoracic spine--a prospective study with ultrasound-based motion analysis.

BACKGROUND: Shoulder complaints, and especially the outlet-impingement syndrome, are a common condition. Among other things, poor posture has been discussed as a cause. A correlation between impingement syndrome and restricted mobility of the thoracic spine (T) has been described earlier, but there has been no motion analysis of the thoracic spine to show these correlations. In the present prospective study, we intended to find out whether there is a significant difference in the thoracic sagittal range of motion (ROM) between patients with a shoulder outlet impingement syndrome and a group of patients who had no shoulder pathology. Secondly, we wanted to clarify whether Ott's sign correlates with ultrasound topometric measurements. METHODS: Two sex- and age-matched groups (2 x n = 39) underwent a clinical and an ultrasound topometric examination. The postures examined were sitting up straight, sitting in maximal flexion and sitting in maximal extension. The disabilities of the arm, shoulder and hand (DASH) score (obtained by means of a self-assessment questionnaire) and the Constant score were calculated. Lengthening and shortening of the dorsal projections of the spine in functional positions was measured by tape with Ott's sign. RESULTS: On examination of the thoracic kyphosis in the erect seated posture there were no significant differences between the two groups (p = 0.66). With ultrasound topometric measurement it was possible to show a significantly restricted segmental mobility of the thoracic spine in the study group compared with the control group (p = 0.01). An in-depth look at the mobility of the subsegments T1-4, T5-8 and T9-12 revealed that differences between the groups in the mobility in the lower two sections of the thoracic spine were significant (T5-8: p = 0.03; T9-12: p = 0.02). The study group had an average Constant score of 35.1 points and the control group, 85.5 (p < 0.001). On the DASH score the patient group reached 34.2 points and the control group, 1.4 (p < 0.001). The results of Ott's sign differed significantly between the two collectives (p = 0.0018), but showed a weak correlation with the ultrasound topometric measurements (study group flexion/extension: r = 0.36/0.43, control group flexion/extension: r = 0.29/0.26). CONCLUSION: The mobility of the thoracic spine should receive more attention in the diagnosis and therapy of patients with shoulder outlet impingement syndrome.

Towards a multidimensional patient reported outcome measures assessment: development and validation of a questionnaire for patients with ankylosing spondylitis/spondyloarthritis.

OBJECTIVE: To assess the validity, reliability and responsiveness to change of a patient self-reported questionnaire that can assess construct outcome measures of patients with ankylosing spondylitis (AS)/spondyloarthritis. METHODS: The questionnaire was developed by integrating information obtained from patients suffering from AS/spondyloarthritis based on the Rasch model. The questionnaire includes assessment of functional disability, quality of life, VAS for spinal pain, joint pain, global status, fatigue, duration of morning stiffness, review of the systems, falls and cardiovascular risks, self-helplessness as well as self-reported joint and soft tissue pain. The questionnaire was completed by 267 consecutive patients with AS (124) and spondyloarthritis (143). RESULTS: The PROMs questionnaire was reliable as demonstrated by a high-standardized alpha. The questionnaire items correlated significantly (p<0.01) with clinical parameters of disease activity. Patient reported tender joints and enthesitis scores correlated significantly with the physician's scores (correlation coefficient 0.848 and 0.821 respectively). Changes in functional disability, quality of life as well as self-helplessness scores showed significant (p<0.01) variation with diseases activity status. The PROMs questionnaire showed also a high degree of comprehensibility (9.3). CONCLUSION: The developed PROMs questionnaire is a reliable and valid instrument for assessment of patients suffering from AS and spondyloarthritis. Being short, rapid and comprehensive, this adds more to its applicability. The data support the value of completion of the simple two pages patient questionnaire, which provides a quantitative written documented record by the patient, at each visit to the rheumatologist.

Use of electrical stimulation and exercise to increase muscle strength in a patient after surgery for cervical spondylotic myelopathy.

Current literature offers little research on the restoration of function in patients following anterior decompression surgery for cervical spondylotic myelopathy. This case report describes the functional outcomes for a physical therapy program using a protocol of alternate day electrical stimulation to hip and knee extensor muscles along with exercise. The protocol, designed to increase lower extremity strength necessary for ambulation in a patient who was status post anterior cervical decompression and fusion surgery, consisted of treatment sessions five times per week for 6 weeks and included electrical stimulation [medium frequency alternating current (MFAC)] in conjunction with active range of motion exercises, followed by functional mobility training and gait training. Outcome measures included Manual Muscle testing, the Functional Independence Measure (FIM), and the Walking Index for Spinal Cord Injuries (WISCI). Improvement was demonstrated in all three measures following the use of the treatment regimen, suggesting there may be a benefit to the use of electrical stimulation and exercise to increase lower extremity strength and improve gait outcomes in this population. Definitive conclusions regarding the correlation between this treatment protocol and the outcomes achieved are limited by the case report design. Carefully designed research studies are needed to demonstrate the effectiveness of the protocol.

Modic changes and interleukin 1 gene locus polymorphisms in occupational cohort of middle-aged men.

According to recent systematic reviews, Modic changes are associated with low-back pain. However, their pathophysiology remains largely unknown. A previous study of Northern Finnish males implicated that IL1A and MMP3 polymorphisms play a role in type II Modic changes. The purpose of the current study was to examine the association of IL1 cluster polymorphisms with Modic changes amongst middle-aged men in Southern Finland. The final study sample consisted of 108 men from three different occupations, who underwent magnetic resonance imaging (MRI) with a 0.1 T-scanner. Six single nucleotide polymorphisms (SNP) in the IL1 gene cluster (IL1A c.1-889C>T; IL1B c.3954C>T; IL1RN c.1812G>A; IL1RN c.1887G>C; IL1RN c.11100T>C; IL1RN c.1506G>A) were genotyped with the SNP-TRAP method or by allele-specific primer extension on modified microarray. In all, 45 subjects had Modic changes at one or more disc levels. The presence of the minor allele of IL1A (c.1-889C>T) was associated with these changes (any Modic change p = 0.031, type II changes p = 0.036). The carriers of the T-allele had a 2.5-fold risk of Modic change and the association was independent of the other IL1 gene cluster loci studied. In addition, a minor haplotype, with a frequency of 7.5% in the study population, including the minor alleles of IL1A c.1-889C>T, IL1RN c.1812G>A, and IL1RN c.1506G>A, was significantly associated with Modic changes. This observation is in accordance with the previous finding from a different geographical area, and thus confirms the importance of the IL1A gene in the pathophysiology of Modic changes.