The Impact of Illness Perceptions and Coping on the Association Between Back Pain and Health Outcomes in Patients Suspected of Having Axial Spondyloarthritis: Data From the SPondyloArthritis Caught Early Cohort.

OBJECTIVE: To investigate whether illness perceptions and coping influence the relationship between back pain and health outcomes in patients suspected of having axial spondyloarthritis (SpA). METHODS: In the SPondyloArthritis Caught Early cohort, regression models were computed at baseline, with back pain intensity (range 0-10) as the determinant and health-related quality of life, the physical component summary score (PCS) and mental component summary (MCS) of the Short Form 36 (SF-36) health survey, or work productivity loss as outcomes. Subsequently, using Leventhal's Common-Sense Model of Self-Regulation, illness perceptions and, thereafter, coping were added to the models. Analyses were repeated for patients diagnosed and classified as having axial SpA according to the Assessment of SpondyloArthritis international Society axial SpA criteria (ASAS axial SpA), patients only diagnosed with axial SpA (axial SpA-diagnosed only), and those with chronic back pain. RESULTS: A total of 424 patients (145 with ASAS axial SpA, 81 with only a diagnosis of axial SpA, and 198 with chronic back pain); 64% of the total group were female, the mean ± SD age was 30.9 ± 8.1 years, and the mean ± SD symptom duration was 13.3 ± 7.1 months) were studied. In all patients, the strength of the associations between back pain and the PCS, back pain and the MCS score, and back pain and loss of work productivity were decreased by adding illness perceptions to the model, but explained variance improved. Adding coping to these models did not change the results. Comparable results were observed in all subgroups. CONCLUSION: Illness perception, but not coping, is important in the relationship between back pain and HRQoL and work productivity loss in patients suspected of having axial SpA, irrespective of subgroup. This finding suggests that targeting illness perceptions could improve health outcomes in patients suspected of having axial SpA.

In Early Axial Spondyloarthritis, Increasing Disease Activity Is Associated with Worsening of Health-related Quality of Life over Time.

OBJECTIVE: In early axial spondyloarthritis (axSpA), data are lacking about the relationship between disease activity and health-related quality of life (HRQOL). We assessed and quantified the association between change in Ankylosing Spondylitis Disease Activity Score (ASDAS) and HRQOL over time in early axSpA. METHODS: Baseline and 1-year data of patients with axSpA fulfilling the Assessment of Spondyloarthritis international Society (ASAS) classification criteria from the SPondyloArthritis Caught Early (SPACE) cohort were analyzed. Associations between change in ASDAS and in physical (PCS) or mental component summary (MCS) of the Medical Outcomes Study Short Form-36 were tested by linear regression models. Age, sex, ASAS criteria arm, and blue- versus white-collar work were tested for effect modification. Subsequently, these factors and medication were tested for confounding. RESULTS: There were 161 patients with axSpA [53% male, mean (± SD) age 29.7 (± 7.5) yrs, symptom duration 13.6 (± 7.2) months, HLA-B27-positive 91%, radiographic sacroiliitis 22%] who had ASDAS of 2.5 (± 1.0) and 2.0 (± 0.8), PCS of 28.4 (± 14.3) and 36.9 (± 13.1), and MCS of 48.2 (± 13.8) and 49.3 (± 12.0) at baseline and 1 year, respectively. Per unit increase in ASDAS between baseline and 1 year, PCS worsened by 9.5 points. The same level of disease activity had fewer adverse effects on physical HRQOL in women and white-collar workers. CONCLUSION: To our knowledge, our data are the first to show that in a broad group of patients with early axSpA, increasing ASDAS is associated with worsening of physical HRQOL, but not mental HRQOL, over time.

Magnetic Resonance Imaging of the Sacroiliac Joints Indicating Sacroiliitis According to the Assessment of SpondyloArthritis international Society Definition in Healthy Individuals, Runners, and Women With Postpartum Back Pain.

OBJECTIVE: To compare magnetic resonance images (MRIs) of the sacroiliac (SI) joints of healthy subjects and individuals with known mechanical strain acting upon the SI joints to those of patients with axial spondyloarthritis (SpA) and patients with chronic back pain. METHODS: Three readers who had received standardized training and were blinded with regard to study group randomly scored MRIs of the SI joints of 172 subjects, including 47 healthy individuals without current or past back pain, 47 axial SpA patients from the Spondyloarthritis Caught Early (SPACE) cohort (with a previous MRI confirmed positive for sacroiliitis), 47 controls with chronic back pain (irrespective of MRI results) from the SPACE cohort, 7 women with postpartum back pain, and 24 frequent runners. MRIs were scored according to the Assessment of SpondyloArthritis international Society (ASAS) definition and Spondyloarthritis Research Consortium of Canada (SPARCC) index. RESULTS: Of the 47 healthy volunteers, 11 (23.4%) had an MRI positive for sacroiliitis, compared to 43 (91.5%) of 47 axial SpA patients and 3 (6.4%) of 47 patients with chronic back pain. Three (12.5%) of the 24 runners and 4 (57.1%) of the 7 women with postpartum back pain had a positive MRI. Using a SPARCC cutoff of ≥2 for positivity, 12 (25.5%) of 47 healthy volunteers, 46 (97.9%) of 47 positive axial SpA patients, 5 (10.6%) of 47 controls with chronic back pain, 4 (16.7%) of 24 runners, and 4 (57.1%) of 7 women with postpartum back pain had positive MRIs. Deep bone marrow edema (BME) lesions were not found in healthy volunteers, patients with chronic back pain, or runners, but were found in 42 (89.4%) of 47 positive axial SpA patients and in 1 (14.3%) of 7 women with postpartum back pain. CONCLUSION: A substantial proportion of healthy individuals without current or past back pain has an MRI positive for sacroiliitis according to the ASAS definition. Deep (extensive) BME lesions are almost exclusively found in axial SpA patients.

Pathophysiology of axial spondyloarthritis: Consensus and controversies.

BACKGROUND: Axial spondyloarthritis (axSpA) is a common inflammatory arthritis of the sacroiliac joints and the spine. The best-known and most studied form of axSpA is ankylosing spondylitis. DESIGN: In this review, we provide a brief overview of the pathophysiology of axSpA. In addition, we performed a quantitative text analysis of reviews on the pathogenesis of axSpA published in the last 10 years to establish the current consensus in various fields of research into the pathogenesis of axSpA. RESULTS: There appears to be broad consensus on genetic risk factors and the involvement of the immune system in the initiation phase of the disease although little consensus was found on which specific immune cells drive disease. Moreover, despite relatively little data available, alterations in the microbiome are commonly thought to be involved in disease. Abnormal bone formation is the most prominent pathogenic factor thought to be involved in disease progression. CONCLUSION: So, although the pathophysiology of axSpA remains incompletely understood, the progress in recent years in several fields of research in axSpA including genetics, diagnosis, imaging and therapeutics, hold great promise for the future.

Low-dose CT detects more progression of bone formation in comparison to conventional radiography in patients with ankylosing spondylitis: results from the SIAS cohort.

OBJECTIVES: To compare the CT Syndesmophyte Score (CTSS) for low-dose CT (ldCT) with the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) for conventional radiographs (CR) in patients with ankylosing spondylitis (AS). METHODS: Patients with AS in the Sensitive Imaging in Ankylosing Spondylitis cohort had lateral cervical and lumbar spine CR and whole spine ldCT at baseline and 2 years. CR and ldCT images were scored by two readers, paired by patient, blinded to time order, per imaging modality. For the total score analysis, we used average scores of readers per corner on CR or quadrant on ldCT. For the syndesmophyte analysis we used individual reader and consensus scores, regarding new or growing syndesmophyte at the same corner/quadrant. RESULTS: 50 patients were included in the syndesmophyte analysis and 37 in the total score analysis. Mean (SD) status scores for mSASSS (range 0-72) and CTSS (range 0-552) at baseline were 17.9 (13.8) and 161.6 (126.6), and mean progression was 2.4 (3.8) and 17.9 (22.1). Three times as many patients showed new or growing syndesmophytes at ≥3 quadrants on ldCT compared with ≥3 corners on CR for individual readers; for consensus this increased to five times. In 50 patients, 36 new or growing syndesmophytes are seen on CR compared with 151 on ldCT, most being found in the thoracic spine. CONCLUSIONS: ldCT, covering the whole spine, detects more progression in the form of new and growing syndesmophytes in patients with AS compared with CR, which is limited to the cervical and lumbar spine. Most progression occurred in the thoracic spine.

Development of the CT Syndesmophyte Score (CTSS) in patients with ankylosing spondylitis: data from the SIAS cohort.

OBJECTIVES: To develop the CT Syndesmophyte Score (CTSS) for low-dose CT (ldCT) to assess structural damage in the spine of patients with ankylosing spondylitis (AS) and test its reliability. METHODS: Patientswith AS in the SIAS cohort had whole spine ldCT at baseline and 2 years. Syndesmophytes were scored in coronal and sagittal planes in eight quadrants per vertebral unit (VU) as absent=0, <50% of the intervertebral disc space (IDS)=1, ≥50%=2 or bridging the IDS=3 (range 0-552). Images were scored by two readers, paired by patient, blinded to time order. Whole spine and spinal segment status and change scores were calculated. Inter-reader reliability was assessed by intraclass correlation coefficient (ICC), smallest detectable change (SDC) and frequency of scores per VU. RESULTS: 49 patients (mean age 50 years (SD 9.8), 84% men, 88% human leucocyte antigen B27 positive) were included. Mean (SD) scores of reader 1 were: whole spine baseline status score 163 (126) and change score 16 (21), spinal segment baseline status scores 30 (41), 97 (77) and 36 (36) and change scores 2 (7), 12 (18) and 3 (4) for the cervical, thoracic and lumbar spine, respectively. Scores of reader 2 were similar. Whole spine status score ICC was 0.99 and 0.97-0.98 for spinal segments. Whole spine change score ICC was 0.77 and 0.32-0.75 for spinal segments. Whole-spine SDC was 14.4. Score distribution pattern per VU was similar between readers. CONCLUSIONS: Using the CTSS, new bone formation in the spine of patients with AS can be assessed reliably. Most progression was seen in the thoracic spine.

Gastrin-releasing peptide contributes to the regulation of adult hippocampal neurogenesis and neuronal development.

In the postnatal hippocampus, newly generated neurons contribute to learning and memory. Disruptions in neurogenesis and neuronal development have been linked to cognitive impairment and are implicated in a broad variety of neurological and psychiatric disorders. To identify putative factors involved in this process, we examined hippocampal gene expression alterations in mice possessing a heterozygous knockout of the calcium/calmodulin-dependent protein kinase II alpha heterozygous knockout gene (CaMK2α-hKO), an established model of cognitive impairment that also displays altered neurogenesis and neuronal development. Using this approach, we identified gastrin-releasing peptide (GRP) as the most dysregulated gene. In wild-type mice, GRP labels NeuN-positive neurons, the lone exception being GRP-positive, NeuN-negative cells in the subgranular zone, suggesting GRP expression may be relevant to neurogenesis and/or neuronal development. Using a model of in vitro hippocampal neurogenesis, we determined that GRP signaling is essential for the continued survival and development of newborn neurons, both of which are blocked by transient knockdown of GRP's cognate receptor (GRPR). Furthermore, GRP appears to negatively regulate neurogenesis-associated proliferation in neural stem cells both in vitro and in vivo. Intracerebroventricular infusion of GRP resulted in a decrease in immature neuronal markers, increased cAMP response element-binding protein (CREB) phosphorylation, and decreased neurogenesis. Despite increased levels of GRP mRNA, CaMK2α-hKO mutant mice expressed reduced levels of GRP peptide. This lack of GRP may contribute to the elevated neurogenesis and impaired neuronal development, which are reversed following exogenous GRP infusion. Based on these findings, we hypothesize that GRP modulates neurogenesis and neuronal development and may contribute to hippocampus-associated cognitive impairment.