Carola Werner

Interobserver reliability of rheumatologists performing musculoskeletal ultrasonography: results from a EULAR “Train the trainers” course

Objective: To evaluate the interobserver reliability among 14 experts in musculoskeletal ultrasonography (US) and to determine the overall agreement about the US results compared with magnetic resonance imaging (MRI), which served as the imaging “gold standard”. Methods: The clinically dominant joint regions (shoulder, knee, ankle/toe, wrist/finger) of four patients with inflammatory rheumatic diseases were ultrasonographically examined by 14 experts. US results were compared with MRI. Overall agreements, sensitivities, specificities, and interobserver reliabilities were assessed. Results: Taking an agreement in US examination of 10 out of 14 experts into account, the overall κ for all examined joints was 0.76. Calculations for each joint region showed high κ values for the knee (1), moderate values for the shoulder (0.76) and hand/finger (0.59), and low agreement for ankle/toe joints (0.28). κ Values for bone lesions, bursitis, and tendon tears were high (κ = 1). Relatively good agreement for most US findings, compared with MRI, was found for the shoulder (overall agreement 81%, sensitivity 76%, specificity 89%) and knee joint (overall agreement 88%, sensitivity 91%, specificity 88%). Sensitivities were lower for wrist/finger (overall agreement 73%, sensitivity 66%, specificity 88%) and ankle/toe joints (overall agreement 82%, sensitivity 61%, specificity 92%). Conclusion: Interobserver reliabilities, sensitivities, and specificities in comparison with MRI were moderate to good. Further standardisation of US scanning techniques and definitions of different pathological US lesions are necessary to increase the interobserver agreement in musculoskeletal US.

Interobserver reliability in musculoskeletal ultrasonography: results from a “Teach the Teachers” rheumatologist course

Objective: To assess the interobserver reliability of the main periarticular and intra-articular ultrasonographic pathologies and to establish the principal disagreements on scanning technique and diagnostic criteria between a group of experts in musculoskeletal ultrasonography. Methods: The shoulder, wrist/hand, ankle/foot, or knee of 24 patients with rheumatic diseases were evaluated by 23 musculoskeletal ultrasound experts from different European countries randomly assigned to six groups. The participants did not reach consensus on scanning method or diagnostic criteria before the investigation. They were unaware of the patients’ clinical and imaging data. The experts from each group undertook a blinded ultrasound examination of the four anatomical regions. The ultrasound investigation included the presence/absence of joint effusion/synovitis, bony cortex abnormalities, tenosynovitis, tendon lesions, bursitis, and power Doppler signal. Afterwards they compared the ultrasound findings and re-examined the patients together while discussing their results. Results: Overall agreements were 91% for joint effusion/synovitis and tendon lesions, 87% for cortical abnormalities, 84% for tenosynovitis, 83.5% for bursitis, and 83% for power Doppler signal; κ values were good for the wrist/hand and knee (0.61 and 0.60) and fair for the shoulder and ankle/foot (0.50 and 0.54). The principal differences in scanning method and diagnostic criteria between experts were related to dynamic examination, definition of tendon lesions, and pathological v physiological fluid within joints, tendon sheaths, and bursae. Conclusions: Musculoskeletal ultrasound has a moderate to good interobserver reliability. Further consensus on standardisation of scanning technique and diagnostic criteria is necessary to improve musculoskeletal ultrasonography reproducibility.

Knee Osteoarthritis Efficacy of a new method of contrast-enhanced musculoskeletal ultrasonography in detection of synovitis in patients with knee osteoarthritis in comparison with magnetic resonance imaging

Objective: To develop a new method of digital synovial vascularisation quantification by using contrast-enhanced musculoskeletal ultrasonography (MUS) in detecting synovitis in patients with knee osteoarthritis (OA) compared with healthy subjects and MRI. Methods: Evaluation of 41 patients with painful knee OA and 6 healthy subjects. The severity of knee pain was evaluated. All patients and all 6 healthy subjects underwent contrast medium-enhanced (CE)-MUS with SonoVue®, and 36 patients additionally underwent CE-MRI with Magnevist. Joint effusion, synovial thickening and pain were assessed and compared with B-mode and Power Doppler sonography (PDS) as well as contrast medium enhancement. Results: Pain evaluated by the visual analogue scale (VAS) hardly correlated with other markers of disease activity measured by ultrasound (US) in B-mode or MRI. US of the superior recess revealed an effusion or synovial thickening in 58%. PDS findings were positive in 63%, and CE-MUS in the superior knee recess was positive in 95%. MRI showed effusion in the superior recess in 61% and showed positive findings in 82% when using contrast medium. The kappa value was 0.48 between US and MRI with regard to the effusion in the superior recess, and 0.53 between PD signal in the superior recess and effusion in the superior recess by US. Using MRI as the reference standard, there was a sensitivity of 72% for assessing effusion in the superior recess and 81% for assessing effusion in the lateral recess. Conclusion: Assessment of disease activity (synovitis) in knee OA by VAS is not sufficient. US PDS was more sensitive than B-mode, and CE-MUS was more sensitive than PDS and CE-MRI in detecting synovitis in patients with painful knee OA. Also, CE-MRI was more sensitive in detecting inflammatory changes in the superior recess than without contrast medium. Using CE-MUS and performing time/intensity analysis has shown to be a good model for evaluation of an inflammatory process in the setting of knee OA in the superior recess.

T2*-weighted MRI in diagnosis of multiple system atrophy : A practical approach for clinicians

BackgroundPutaminal iron deposition is a histopathological feature of multiple system atrophy (MSA), which is not observed in patients with idiopathic Parkinson’s disease (PD). T2*-weighted magnetic resonance imaging (MRI) gradient echo (GE) sequences are sensitive for paramagnetic susceptibility changes and therefore may support the clinical differential diagnosis between MSA and PD.MethodsWe evaluated putaminal signal intensities on 1.0 Tesla scans of 52 MSA patients, 88 patients with PD and 29 healthy control subjects.ResultsThe typical finding in T2* GE sequences of MSA patients was a signal loss of the dorsolateral putamen, which showed a high specificity (>0.91), but was present in only a subpopulation of patients (sensitivity 0.64–0.69). The combination of the latter with additional presence of a hyperintense lateral rim in fluid attenuated inversion recovery (FLAIR) sequences increased the specificity to 0.97. Using a quantitative evaluation of putaminal signal intensities in defined regions of interest MSA and PD could be discriminated with a diagnostic accuracy (r) of up to 0.82.ConclusionAlthough the separation of groups remains incomplete, the use of T2*-weighted GE sequences combined with FLAIR may be helpful for the differential diagnosis of MSA versus PD considering its fast application, easy evaluation, broad availability, the specificity of findings and the presence of putaminal signal loss already at early disease stages.

Clindamycin is neuroprotective in experimental Streptococcus pneumoniae meningitis compared with ceftriaxone

In animal models of Streptococcus pneumoniae meningitis, rifampin is neuroprotective in comparison to ceftriaxone. So far it is not clear whether this can be generalized for other protein synthesis‐inhibiting antimicrobial agents. We examined the effects of the bactericidal protein synthesis‐inhibiting clindamycin (n = 12) on the release of proinflammatory bacterial components, the formation of neurotoxic compounds and neuronal injury compared with the standard therapy with ceftriaxone (n = 12) in a rabbit model of pneumococcal meningitis. Analysis of the CSF and histological evaluation were combined with microdialysis from the hippocampal formation and the neocortex. Compared with ceftriaxone, clindamycin reduced the release of lipoteichoic acids from the bacteria (p = 0.004) into the CSF and the CSF leucocyte count (p = 0.011). This led to lower extracellular concentrations of hydroxyl radicals (p = 0.034) and glutamate (p = 0.016) in the hippocampal formation and a subsequent reduction of extracellular glycerol levels (p = 0.018) and neuronal apoptosis in the dentate gyrus (p = 0.008). The present data document beneficial effects of clindamycin compared with ceftriaxone on various parameters linked with the pathophysiology of pneumococcal meningitis and development of neuronal injury. This study suggests neuroprotection to be a group effect of bactericidal protein synthesis‐inhibiting antimicrobial agents compared with the standard therapy with β‐lactam antibiotics in meningitis.

Impact of Breast Density on Computer-Aided Detection in Full-Field Digital Mammography

The goal of this study was to evaluate the performance of a computer-aided detection (CAD) system in full-field digital mammography (Senographe 2000D, General Electric, Buc, France) in finding out carcinomas depending on the parenchymal density. A total of 226 mediolateral oblique (MLO) and 186 craniocaudal (CC) mammographic views of histologically proven cancers were retrospectively evaluated with a digital CAD system (ImageChecker V2.3 R2 Technology, Los Altos, CA, USA). Malignant tumors were detected correctly by CAD in MLO view in 84.85% in breasts with parenchymal tissue density of the American College of Radiology (ACR) type 1, in 70.33% of the ACR type 2, in 68.12% of the ACR type 3, and in 69.70% of the ACR type 4. For the CC view, similar results were found according to the ACR types. Using the chi-square and McNemar tests, there was no statistical significance. However, a trend of better detection could be seen with decreasing ACR type. In conclusion, there seems to be a tendency for breast tissue density to affect the detection rate of breast cancer when using the CAD system.

Computer-aided detection in full-field digital mammography: detection in dependence of the BI-RADS categories.

Abstract:  The object of this study was to determine the performance of a computer‐aided detection system in full‐field digital mammography (Senographe 2000D, General Electric, Buc, France) in detecting carcinomas in breasts in dependence of the initial Breast Imaging Reporting and Data System (BI‐RADS) categories. A total of 226 mediolateral oblique (MLO) and 186 craniocaudal (CC) view mammograms of histologically proven cancers were retrospectively evaluated with a primary digital computer‐aided detection system (Image Checker V2.3; R2 Technology, Los Altos, CA). According to BI‐RADS of the American College of Radiology (ACR), the lesions were classified in MLO view as BI‐RADS 1 in 2 cases, BI‐RADS 2 in 11 cases, BI‐RADS 3 in 37 cases, BI‐RADS 4 in 56 cases, and BI‐RADS 5 in 120 cases, and in CC view as BI‐RADS 1 in 2 cases, BI‐RADS 2 in 8 cases, BI‐RADS 3 in 26 cases, BI‐RADS 4 in 46 cases, and BI‐RADS 5 in 104 cases. The computer‐aided detection system shows markers also in mammograms classified as BI‐RADS categories 1–3 by the radiologist. Furthermore, BI‐RADS categories 4 and 5 in most cases demonstrate masses in mammography. With increasing BI‐RADS category, the computer‐aided detection system shows decreasing numbers of overlooked carcinomas. In MLO view, no markers were found in 100% (2/2), 81.8% (9/11), 59.5% (22/37), 46.4% (26/56), and 15% (18/120) for BI‐RADS categories 1–5, respectively. False‐positive markers, however, were seen in 0.5 per image (205/412). In conclusion, the high rate of false‐positive markers shows that the specificity of the computer‐aided detection system is limited and that improvements are necessary. 

Reliability exercise for the polymyalgia rheumatica classification criteria study: the oranjewoud ultrasound substudy.

Objective. A study supported by the EULAR and the ACR being conducted to establish classification criteria for polymyalgia rheumatica (PMR) will include ultrasound examination of the shoulders and hips. Ultrasound (US) depicts glenohumeral joint effusion, biceps tenosynovitis, subdeltoid bursitis, hip joint synovitis, and trochanteric bursitis in PMR. These findings may aid in distinguishing PMR from other diseases. The purpose of this study was to assess standards and US interreader agreement of participants in the PMR classification criteria study. Methods. Sixteen physicians in four groups examined shoulders and hips of 4 patients and 4 healthy adults with ultrasound. Overall agreement and interobserver agreement were calculated. Results. The overall agreement (OA) between groups was 87%. The OA for healthy shoulders was 88.8%, for healthy hips 100%, for shoulders with pathology 85.2%, and 74.3% for hips with pathology, respectively. Conclusion. There was a high degree of agreement found for the examination of healthy shoulders and pathologic hips. Agreement was moderate for pathologic shoulders and perfect for healthy hips. US of shoulder and hips performed by different examiners is a reliable and feasible tool for assessment of PMR related disease pathology and can be incorporated into a classification criteria study.

Nonparametric methods for analysing the accuracy of diagnostic tests with multiple readers

The evaluation of diagnostic agents or imaging procedures is governed by the same scientific and regulatory rules as that of other medical products. Receiver operating characteristic (ROC) curves, and especially the area under these ROC curves, are indices for the accuracy of a diagnostic test for continuous as well as ordinal data. The methodology of multivariate rank statistics for the nonparametric Behrens-Fisher problem is used to evaluate the accuracy of a diagnostic test in a complex factorial design with repeated measurements. Hypotheses are formulated by means of relative treatment effects and are tested by a multivariate extension of the Mann-Whitney statistic in a heteroscedastic model. The application of this method is demonstrated by the analysis of a data set from a diagnostic clinical trial.

Movement disturbances in the differential diagnosis of Creutzfeldt‐Jakob disease

Movement disturbances are common in dementia disorders and are a central feature of the clinical classification criteria of Creutzfeldt‐Jakob disease (CJD). Polymorphism at codon 129 of the prion protein gene is known to determine the clinical picture of CJD. The frequency and characteristics of movement disturbances in other dementing disorders, such as Alzheimers disease (AD), is barely known and leads to misdiagnoses. We investigated the occurrence and characteristics of movement disturbances in 143 patients neuropathologically confirmed with CJD (n = 100), AD (n = 29), dementia with Lewy bodies (DLB) (n = 7), or other diagnoses (n = 7). All patients had been referred with the differential diagnosis of prion disease. Ataxia and dysmetria were significantly more frequent in CJD than in AD or DLB patients, whereas hypokinesia was up to five times more frequent in AD or DLB (P < 0.05). Using an ordered logistic regression to identify constellations of movement disturbances, the diagnosis of CJD was likely in patients presenting ataxia but not hypokinesia. The reverse situation was statistically associated with AD. Ataxia and cogwheel rigidity were associated with valine‐homozygosity and akinesia with methionine‐homozygosity in the CJD patients. Our results indicate that the careful assessment of movement disturbances may be helpful in the differential diagnosis of Creutzfeldt‐Jakob disease.