Can rheumatologists unequivocally diagnose axial spondyloarthritis in patients with chronic back pain of less than 2 years duration? Primary outcome of the 2-year SPondyloArthritis Caught Early (SPACE) cohort.

OBJECTIVES: To investigate the prevalence of axial spondyloarthritis (axSpA) in patients with chronic back pain (CBP) of less than 2 years (2y) duration referred to the rheumatologist, the development of diagnosis over time, and patient characteristics of those developing definite (d-)axSpA over 2y. METHODS: We analysed the 2y data from SPondyloArthritis Caught Early, a European cohort of patients (<45 years) with CBP (≥3 months, ≤2y) of unknown origin. The diagnostic workup comprised evaluation of clinical SpA features, acute phase reactants, HLA-B27, radiographs and MRI (sacroiliac joints and spine), with repeated assessments. At each visit (baseline, 3 months, 1y and 2y), rheumatologists reported a diagnosis of axSpA or non-axSpA with level of confidence (LoC; 0-not confident at all to 10-very confident). MAIN OUTCOME: axSpA diagnosis with LoC≥7 (d-axSpA) at 2y. RESULTS: In 552 patients with CBP, d-axSpA was diagnosed in 175 (32%) at baseline and 165 (30%) at 2y. Baseline diagnosis remained rather stable: at 2y, baseline d-axSpA was revised in 5% of patients, while 8% 'gained' d-axSpA. Diagnostic uncertainty persisted in 30%. HLA-B27+ and baseline sacroiliitis imaging discriminated best 2y-d-axSpA versus 2y-d-non-axSpA patients. Good response to non-steroidal anti-inflammatory drugs and MRI-sacroiliitis most frequently developed over follow-up in patients with a new d-axSpA diagnosis. Of the patients who developed MRI-sacroiliitis, 7/8 were HLA-B27+ and 5/8 male. CONCLUSION: A diagnosis of d-axSpA can be reliably made in nearly one-third of patients with CBP referred to the rheumatologist, but diagnostic uncertainty may persist in 5%-30% after 2y. Repeated assessments yield is modest, but repeating MRI may be worthwhile in male HLA-B27+ patients.

Do fatty lesions explain the effect of inflammation on new syndesmophytes in patients with radiographic axial spondyloarthritis? Results from the SIAS cohort and ASSERT trial.

OBJECTIVES: To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition. METHODS: Patients with radiographic axial spondyloarthritis (r-axSpA) from the SIAS (Sensitive Imaging in Ankylosing Spondylitis) cohort and ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial were assessed at T0, T1 (SIAS: 1 year; ASSERT: 24 weeks) and T2 (2 years). Syndesmophytes assessed in each vertebral corner by whole spine low-dose CT (SIAS) or spinal radiographs (ASSERT) at T0 and T2 were considered present if seen by two of two readers. Inflammation (T0) and fat deposition (T0 and T1) on MRI were present if seen by ≥2 of 3 readers (SIAS) or 2 of 2 readers (ASSERT). Vertebral corners showing fat deposition or a syndesmophyte at baseline were ignored. Mediation analysis was applied to determine what proportion of the total effect of inflammation on syndesmophyte formation could be explained via the path of intermediate fat deposition. RESULTS: Forty-nine SIAS patients (with 2667 vertebral corners) and 168 ASSERT patients (with 2918 vertebral corners) were analysed. The presence of inflammation at T0 increased the probability of a new syndesmophyte in the same vertebral corner at T2 by 9.3%. Of this total effect, 0.2% (2% (0.2 of 9.3) of the total effect) went via intermediate new fat deposition. In ASSERT, the total effect was 7.3%, of which 0.8% (10% of the total effect) went via new fat deposition. CONCLUSION: In r-axSpA, vertebral corner inflammation may lead to syndesmophyte formation but in a minority of cases via visible fat deposition.

Good construct validity of the CT Syndesmophyte Score (CTSS) in patients with radiographic axial spondyloarthritis.

OBJECTIVES: To assess construct validity of the CT Syndesmophyte Score (CTSS) for the measurement of structural spinal damage in patients with radiographic axial spondyloarthritis. METHODS: Low-dose CT and conventional radiography (CR) were performed at baseline and 2 years. CT was assessed with CTSS by two readers and CR with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by three readers. Two hypotheses were tested: (1) syndesmophytes scored with CTSS are also detected with mSASSS at baseline or 2 years later; (2) CTSS is non-inferior to mSASSS in correlations with spinal mobility measures. Presence of a syndesmophyte was determined per reader per corner for all anterior cervical and lumbar corners on CT at baseline and CR at baseline and 2 years. Correlations of CTSS and mSASSS with six spinal/hip mobility measurements plus Bath Ankylosing Spondylitis Metrology Index (BASMI) were tested. RESULTS: Data from 48 patients (85% male, 85% HLA-B27+, mean age 48 years) were available for hypothesis 1 and 41/48 were available for hypothesis 2. At baseline, syndesmophytes were scored with CTSS in 348 (reader 1, 38%) and 327 (reader 2, 36%) corners out of 917. Of these, depending on reader pairs, 62%-79% were also seen on CR at baseline or after 2 years. CTSS correlated well (rs 0.46-0.73), and with higher correlation coefficients than mSASSS (rs 0.34-0.64), with all spinal mobility measures and BASMI. CONCLUSIONS: The good agreement between syndesmophytes detected by CTSS and mSASSS and the strong correlation of CTSS with spinal mobility support the construct validity of the CTSS.

Inflammation, bone loss and 2-year bone formation at the same vertebra in axial spondyloarthritis: a multilevel MRI and low-dose CT analysis.

OBJECTIVE: To investigate whether in radiographic axial spondyloarthritis (r-axSpA) inflammation is associated with lower trabecular bone density (TBD), and subsequently, if a lower TBD increases the likelihood of 2-year bone formation at the same vertebra. METHODS: Whole spine (C3-L5) data from patients included in the multicentre 2-year Sensitive Imaging in Ankylosing Spondylitis cohort was used. Two readers measured baseline TBD by Hounsfield units (HU) on low-dose CT (ldCT). Baseline MRI bone marrow oedema (BME) status scores and ldCT syndesmophyte formation and/or growth change-from-baseline scores were assessed by three and two readers, respectively. Average of readers' continuous measurements or readers' agreement in binary scores generated within the same vertebra (1-present in ≥1 quadrant/0-absent in all quadrants) were used. Multilevel generalised estimating equations models were used, the unit of analysis being the vertebra. RESULTS: In 50 patients with r-axSpA, TBD HU decreased from cranial to caudal vertebrae. Baseline MRI-BME was present in 300/985 (30%) and syndesmophytes in 588/910 (65%) vertebrae, both most prevalent at thoracolumbar region. Syndesmophyte formation or growth was observed in 18% of at-risk vertebrae (124/691). A significant confounder-adjusted association was found between inflammation and lower TBD (regression coefficient=-51; 95% CI-63 to -39). TBD was not associated with 2-year syndesmophyte formation or growth (adjusted OR 1.00; 95% CI 0.99 to 1.00). CONCLUSION: In r-axSpA, while vertebral inflammation was associated with lower vertebral TBD, lower vertebral TBD itself did not increase the risk for new bone formation at the same vertebra. In preventing syndesmophyte progression, targeting local inflammation seems more important than targeting vertebral trabecular bone loss.

Role of vertebral corner inflammation and fat deposition on MRI on syndesmophyte development detected on whole spine low-dose CT scan in radiographic axial spondyloarthritis.

OBJECTIVES: To investigate the associations between MRI detected vertebral corner inflammation (VCI) and vertebral corner fat deposition (VCFD) on whole spine low-dose CT scan (ldCT) detected syndesmophyte formation and growth. METHODS: Patients from the Sensitive Imaging in Ankylosing Spondylitis cohort underwent MRI (baseline, 1 year and 2 years) and ldCT (baseline and 2 years). MR images were scored by three readers for VCI and VCFD, MRI patterns were defined by presence of VCI and/or VCFD over 2 years. LdCT images were scored by two central readers for presence and size of syndesmophytes and change was calculated for new or new/grown syndesmophytes. Multilevel generalised estimated equations were used to test the associations between VCI and VCFD and syndesmophyte development. RESULTS: Fifty radiographic patients with axial spondyloarthritis were included (mean age 49 years, 86% male, 78% HLA-B27+). Absence of both VCI and VCFD protected against syndesmophyte development (ORs 0.36-0.37). Presence of VCI and/or VCFD increased the risk of syndesmophyte development (ORs 1.73-2.60). Out of all corners with a new or new/grown syndesmophyte, 47% of corners according to reader 1 and 44% according to reader 2 had neither VCI nor VCFD preceding the bone formation. CONCLUSIONS: VCI and VCFD were positively associated with syndesmophyte development. This has been shown for the first time for syndesmophytes detected on ldCT and also in the thoracic spine. However, almost half of all bone formation occurred in corners without VCI or VCFD, suggesting the presence of these lesions in yearly MRIs does not fully clarify the development of syndesmophytes.

Associations between syndesmophytes and facet joint ankylosis in radiographic axial spondyloarthritis patients on low-dose CT over 2 years.

OBJECTIVES: In radiographic axial spondyloarthritis (r-axSpA), spinal damage manifests as syndesmophytes and facet joint ankylosis (FJA). We evaluated whether the presence of one lesion increased the risk of the other lesion. METHODS: Patients with r-axSpA underwent low-dose CT (ldCT) and MRI of the whole spine at baseline and 2 years. On ldCT, vertebrae were scored for presence and size of syndesmophytes; facet joints were assessed for ankylosis. MR images were assessed for inflammation. Two hypotheses were tested: (i) presence of FJA is associated with new syndesmophyte(s) on the same vertebral unit (VU) 2 years later, and (ii) presence of bridging syndesmophyte(s) is associated with new FJA on the same VU 2 years later. Two generalized estimating equations models were tested per hypothesis using increase of FJA/syndesmophytes (model A) or presence of FJA/syndesmophytes (model B) as outcome, adjusted for inflammation at baseline. Secondary analyses tested the hypotheses with outcomes on adjacent VUs and dose-response effects. RESULTS: Fifty-one patients were included (mean age 49, 84% male, 82% HLA-B27+). Baseline bridging syndesmophytes occurred more often (range: 10-60% per VU) than FJA (range: 8-36%). Odds ratios (ORs) (95% CI) for presence of bridging syndesmophytes on development of FJA were 3.55 (2.03, 6.21) for model A and 3.30 (2.14, 5.09) for model B. ORs for presence of baseline FJA on new syndesmophytes were 1.87 (1.20, 2.92) for model A and 1.69 (0.88, 3.22) for model B. Secondary analyses yielded positive ORs for both hypotheses. CONCLUSIONS: Bone formation in vertebrae and in facet joints influence each other's occurrence, with the effect of syndesmophytes being larger than that of FJA.

Facet joint ankylosis in r-axSpA: detection and 2-year progression on whole spine low-dose CT and comparison with syndesmophyte progression.

OBJECTIVES: To evaluate the occurrence and progression of facet joint ankylosis in the whole spine using low-dose CT (ldCT) in radiographic axial spondyloarthritis (r-axSpA) and compare progression of facet joint ankylosis and syndesmophytes. METHODS: Patients with r-axSpA from the Sensitive Imaging in Ankylosing Spondylitis (SIAS) cohort underwent ldCT at baseline (n = 60) and 2 years (n = 53). Facet joints (right and left, levels C2-S1) were scored as ankylosed, not ankylosed or unable to assess. Joints that were frequently poorly visible (>15% missing), were excluded. Inter-reader reliability on the patient level was assessed with intraclass correlation coefficients (ICCs) and smallest detectable change (SDC). Ankylosis was assessed at joint level and patient level for both timepoints. Syndesmophytes were assessed with CT syndesmophyte score. RESULTS: Levels C5-T2 were difficult to assess and excluded from all further analyses. Facet joint ICCs were good to excellent for status scores (0.72-0.93) and poor to excellent for progression scores (0.10-0.91). Facet joint ankylosis was detected at every level but most frequently in the thoracic joints. In total, 48% of patients showed 2-year progression. Most progression occurred in the thoracic segment. Using SDCs as cutoff, 18% of patients had progression of facet joint ankylosis only, whereas 20% of patients had progression of syndesmophytes only. CONCLUSION: This is the first study evaluating facet joints in the whole spine by ldCT in r-axSpA. Facet joint ankylosis was detected most often in the thoracic spine. Assessing facet joints in addition to syndesmophytes detected substantially more patients with damage progression over two years.

Single-case Design Studies in Children with Cerebral Palsy: A Scoping Review.

Aim: To critically evaluate single-case design (SCD) studies performed within the population of children/adolescents with cerebral palsy (CP).Methods: A scoping review of SCD studies of children/adolescents with CP. Demographic, methodological, and statistical data were extracted. Articles were evaluated using the Risk of Bias in N-of-1 Trials (RoBiNT) Scale and the Consolidated Standards of Reporting Trials (CONSORT) extension for N-of-1 trials (CENT 2015). Comments regarding strengths and limitations were analyzed.Results: Studies investigated the effects of a wide range of interventions on various outcomes. Most SCD types were adopted in multiple studies. All studies used visual inspection rather than visual analysis, often complemented with basic statistical descriptives. Risk of bias was high, particularly concerning internal validity. Many CENT items were insufficiently reported. Several benefits and limitations of SCD were identified.Conclusions: The quality of evidence from results of SCD studies needs to be increased through risk of bias reduction.