Enthesitis in a European registry-based cohort of patients with psoriatic arthritis treated with tumour necrosis factor inhibitors: clinical burden, patient-reported outcomes, and treatment response.

OBJECTIVE: To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response. METHOD: Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up. RESULTS: Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63-80%) than at MASES sites (mainly axial; 82-100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis. CONCLUSION: Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.

Greater trochanteric pain syndrome: predicting who will respond to a local glucocorticoid injection.

Objectives: This study aimed to explore whether certain clinical tests or a rapid improvement in lateral hip pain following periarticular injection are predictive of subsequent efficacy of local glucocorticoid (GC) injection in greater trochanteric pain syndrome (GTPS).Method: This secondary analysis of a randomized controlled trial of an injection of GC and local anaesthetic (LA) versus placebo included 44 patients with GTPS. Two subgroups of patients were defined: (i) 30 min responders, reporting a decrease of ≥ 50% of the initial pain at 30 min post-injection; and (ii) positive triple test, presenting a combination of three positive clinical tests (30-second single-leg stance, FABER, and Lequesne). Median level of numeric rating scale for pain at 1 month was the primary outcome. Interaction analysis of treatment effect in the subgroups was performed using a linear regression adjusting for pain at baseline.Results: Sixteen patients (36%) were 30 min responders. In this group, GC treatment was associated with a significant improvement in pain at 1 month compared to non-responders (p = 0.03). The 30 min response was not associated with the use of LA. Positive triple test (22% of patients) was associated with higher pain scores at baseline (p = 0.03). In this group, patients who received placebo had significantly more pain at 1 month than those with the cortisone injection (p = 0.04).Conclusion: Patients with GTPS who present a rapid decrease in pain after periarticular injection, and those who display a combination of three specific clinical tests, are more likely to benefit from an injection with GC and anaesthetic.

[Greater trochanteric pain syndrome]. / "Périarthrite de la hanche".

Trochanteric bursitis, also known as "greater trochanter pain syndrome", is a frequent and often under-diagnosed cause of pain in the lateral hip region. The diagnosis is essentially based on the clinical examination; however various forms of imaging may be useful to confirm the diagnosis and particularly to ex- clude other aetiologies. The different therapeutic options include non-steroidal anti-inflammatories, physiotherapy, local injections of cortisone and local anaesthetic, and extra-corporeal shock wave therapy. Surgical intervention is only indicated in rare cases.

[Pigmented villonodular synovitis]. / La synovite villonodulaire.

Pigmented villonodular synovitis (PVNS), also known as tenosynovial giant cell tumour is an articular pathology that occurs predominantly in young adults and is caused by an abnormal proliferation of the synovial membrane. The clinical presentation includes pain and joint swelling. MRI represents the best imaging modality to investigate this disease but the histopathology of synovial tissue provides the definitive diagnosis. The management of PVNS is often difficult due to the high risk of relapse after treatment. The objective of this article is to review the literature regarding the diagnosis and therapy of this poorly understood condition.

The effect of alcohol on radiographic progression in rheumatoid arthritis.

OBJECTIVE: Alcohol consumption reduces the risk of development of rheumatoid arthritis (RA) and significantly attenuates the development of erosive arthritis in animal models. It remains unknown whether alcohol consumption influences joint damage progression in RA. This study was undertaken to compare the rates of radiographic damage progression in alcohol drinkers and nondrinkers in a large prospective cohort of patients with RA. METHODS: All patients in the population-based Swiss Clinical Quality Management in RA registry database with at least 2 sequential radiographs were included. Joint erosions were assessed in 38 joints in the hands and feet using a validated scoring method. The rate of progression of erosions was analyzed using multivariate regression models for longitudinal data and was adjusted for potential confounders. RESULTS: The study included 2,908 patients with RA with a mean of 4 sequential radiographs and 3.9 years of followup. A trend toward reduced radiographic progression existed in drinkers compared with nondrinkers, with a mean rate of erosive progression of 0.99% (95% confidence interval [95% CI] 0.89-1.09) and 1.13% (95% CI 1.01-1.26) at 1 year, respectively. Alcohol consumption displayed a J-shaped dose-response effect, with a more favorable evolution in occasional consumers (P = 0.01) and daily consumers (P = 0.001) as compared with nondrinkers, while heavy drinkers demonstrated worse radiographic evolution (P = 0.0001). We found significant effect modification by sex, with male drinkers displaying significantly less erosive progression compared with male nondrinkers (mean 0.86% [95% CI 0.70-1.03] versus 1.35% [95% CI 1.02-1.67]; P = 0.007). CONCLUSION: Our findings indicate a trend toward reduced radiographic progression in alcohol drinkers compared with nondrinkers, specifically in occasional and daily alcohol consumers. In particular, male patients with RA who consume alcohol demonstrate less radiographic progression than do male nondrinkers.

Apolipoprotein A-I and platelet factor 4 are biomarkers for infliximab response in rheumatoid arthritis.

OBJECTIVES: The use of biologicals such as infliximab has dramatically improved the treatment of rheumatoid arthritis (RA). However, factors predictive of therapeutic response need to be identified. A proteomic study was performed prior to infliximab therapy to identify a panel of candidate protein biomarkers of RA predictive of treatment response. METHODS: Plasma profiles of 60 patients with RA (28 non-responders (as defined by the American College of Rheumatology 20% improvement criteria (ACR20)) negative and 32 responders (ACR70 positive) to infliximab) were studied by surface enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS) technology on two types of arrays, an anion exchange array (SAX2) and a nickel affinity array (IMAC3-Ni). Biomarker characterisation was carried out using classical biochemical methods (purification by ammonium sulfate precipitation or metal affinity chromatography) and identification by matrix assisted laser desorption/ionisation time-of-flight (MALDI-TOF) MS analysis. RESULTS: Two distinct protein profiles were observed on both arrays and several proteins were differentially expressed in both patient populations. Five proteins at 3.86, 7.77, 7.97, 8.14 and 74.07 kDa were overexpressed in the non-responder group, whereas one at 28 kDa was increased in the responder population (sensitivity>56%, specificity>77.5%). Moreover, combination of several biomarkers improved the sensitivity and specificity of the detection of patient response to over 97%. The 28 kDa protein was characterised as apolipoprotein A-I and the 7.77 kDa biomarker was identified as platelet factor 4. CONCLUSIONS: Six plasma biomarkers are characterised, enabling the detection of patient response to infliximab with high sensitivity and specificity. Apolipoprotein A-1 was predictive of a good response to infliximab, whereas platelet factor 4 was associated with non-responders.

Spatial vision in Alzheimer's disease. General findings and a case report.

Visual contrast sensitivity to sinusoidal gratings of five spatial frequencies was measured in 15 patients with Alzheimer's disease and in eight control subjects. Contrast sensitivity thresholds were elevated at all frequencies in 14 patients compared with control subjects. The 15th patient was unique: she had an impairment in object and face recognition so severe that she could not recognize her husband visually. Her sensitivity to low and intermediate frequencies was markedly reduced in relation to that of other patients, whereas her sensitivity to the highest frequency tested equaled theirs. These observations emphasize the importance of low spatial frequency information for visual object and face recognition.

Implicit learning in patients with probable Alzheimer's disease.

The purpose of the present study was to determine whether patients with probable Alzheimer's disease (AD) were capable of implicit procedural learning. AD patients and elderly control subjects were given a serial visual reaction time task with an embedded repeating sequence. The AD patients responded more slowly than the controls, but many nonetheless showed learning of the repeating sequence. Patients who failed to learn the sequence were similar in age and overall severity of dementia to those who learned, but they scored lower on some tasks of nonverbal reasoning.

Neurochemical dissociation of memory systems.

The administration of scopolamine, an anticholinergic drug, reduced the ability to recall and recognize stimuli presented previously--abilities thought to require declarative memory. In contrast, measures of procedural memory were unaffected by scopolamine: performance on a serial reaction time task incorporating a repeating stimulus and response sequence showed no difference in acquisition and retention of the sequence after scopolamine or saline. These results suggest that the cholinergic system is required for declarative but not procedural memory.

Procedural learning is impaired in Huntington's disease: evidence from the serial reaction time task.

The purpose of the study was to test the hypothesis that Huntington's disease (HD) is associated with impairment of procedural learning. We identified 13 patients with mild to moderate HD whose manual performance was still sufficiently intact to assess learning on the serial reaction time (SRT) task. Twelve age-matched neurologically normal control subjects were studied as well. The SRT task was a four-choice reaction time task in which the stimuli followed a sequence (10 items in length) which repeated itself 10 times during each of the first four blocks of trials. During the fifth block of trials, the stimuli were random. Learning was manifested by a reduction in response latency over the first four blocks and an increase in response latency in the fifth (random) block. Learning in this task has been demonstrated in other amnesics of other etiologies. The HD patients were significantly impaired on sequence-specific learning, using the log-transformed reaction time data (P less than 0.004). In addition, in an individual-by-individual analysis, five of the HD patients and none of the control subjects failed to show sequence-specific learning, a difference in proportions that was significant (P less than 0.04). No feature of the standard cognitive or motor assessment of the HD patients was associated with efficacy of procedural learning. HD, including patients with mild disease, was associated with a deficit in procedural learning, consistent with the hypothesis that the striatum plays a critical role in supporting procedural learning.

Explicit and implicit remembering: when is learning preserved in amnesia?

Amnesic patients can learn and retain a variety of skills. To investigate what distinguishes tasks that are within the learning abilities of amnesic patients from those that are not, we administered two tests to individuals with Korsakoff's syndrome and two control groups. One was a visual reaction time task with an embedded repeating sequence of stimulus positions. Response times of Korsakoff patients indicated that they learned this sequence and retained it normally for a week. The second task was a tactual stylus maze in which all blind alleys were blocked. Korsakoff patients were impaired in learning this maze, as assessed by the time required to trace it. Differences between the two tasks are outlined and the implications of these differences are discussed.

Selective attention in Alzheimer's disease: CSF correlates of behavioral impairments.

CSF levels of HVA, 5-HIAA, and free MHPG, the major metabolites of dopamine, serotonin, and norepinephrine respectively, were measured in 22 patients with AD. These 22 patients were also administered tests of picture-recognition and attentional focusing as part of an earlier experiment. A significant association between deficits in attentional focusing and reduced levels of free MHPG in CSF was noted. These results suggest that behavioral measures can identify patients with noradrenergic involvement.

Selective attention in Alzheimer's disease: characterizing cognitive subgroups of patients.

Picture recognition was studied in 20 patients with AD and in 20 control subjects, using a procedure that matched these groups for initial performance. The groups did not differ significantly in overall forgetting, although 10 patients displayed improved recognition performance 72 hr after learning. These same patients were impaired in a test of attentional focusing, as revealed by post hoc analyses. A predictive experiment involving 20 new patients with AD confirmed the initial findings: a subgroup of patients displayed improved recognition performance 72 hr after learning and impairments in attentional focusing. Neuropsychological tests thus identify a subgroup of patients with impaired selective attention, perhaps related to locus coeruleus neuropathology.

Chromatic information processing.

The investigation of visual processing mediated solely by chromatic information requires conditions preventing a subject's use of the luminance differences normally accompanying a chromatic change. In Experiment 1, which involved a discriminative reaction time (RT) task, chromatic and white stimuli of the same luminance were presented on a dimmer achromatic background. Subjects were instructed to respond only to the chromatic stimuli. RT was slowest at 570 nm and somewhat faster to short wavelengths than to long wavelengths. In Experiment 2, which compared two discriminative RT tasks, RT was faster when subjects responded to color than when they responded to white. Experiments 3 and 4 demonstrated that a brighter white surround decreased the perceived brightness of chromatic stimuli as well as their perceptual similarity to white, but did not affect RT. The results are discussed in terms of the response strength of the chromatic processing channel.

Attentional processing and the independence of color and orientation.

Judgments of the color and shape of a stimulus specified by a cue indicating its location demonstrate stochastic independence. Evidence for the independence of color and orientation was obtained when the cue followed stimulus offset immediately, the cue followed stimulus offset by 2 s, and when either a central or peripheral precue focused attention on the cued stimulus at the time of its presentation. It appears that an object's color and orientation are represented independently even following the attentional focusing thought to support feature integration.

On the development of procedural knowledge.

Amnesic patients demonstrate by their performance on a serial reaction time task that they learned a repeating spatial sequence despite their lack of awareness of the repetition (Nissen & Bullemer, 1987). In the experiments reported here, we investigated this form of procedural learning in normal subjects. A subgroup of subjects showed substantial procedural learning of the sequence in the absence of explicit declarative knowledge of it. Their ability to generate the sequence was effectively at chance and showed no savings in learning. Additional amounts of training increased both procedural and declarative knowledge of the sequence. Development of knowledge in one system seems not to depend on knowledge in the other. Procedural learning in this situation is neither solely perceptual nor solely motor. The learning shows minimal transfer to a situation employing the same motor sequence.

Implicit learning of new verbal associations.

Implicit learning of a series of new verbal associations was studied in four experiments. The first two experiments demonstrated that learning of a repeating sequence of verbal stimuli may occur without awareness, but only when the stimulus-response mapping requires an attention-demanding activity: Subjects who were unaware of the sequence learned when instructed to categorize the stimuli, but not when instructed simply to read them. However, in both situations, unaware subjects performed no better than untrained control subjects in expressing their knowledge of the sequence explicitly. In Experiments 3 and 4, subjects showed implicit learning when the task involved either motor responses to verbal stimuli or verbal responses to spatially arranged stimuli. These findings are discussed in terms of the conditions under which implicit learning can be obtained. First, they demonstrate implicit learning of a set of new associations in the verbal domain. Second, the data suggest that attention is important in implicit learning. Finally, the degree of interitem organization that is familiar preexperimentally seems to partially determine the amount of implicit learning.

Radiographic changes in the knee after meniscal transplantation. An experimental study in a sheep model.

Meniscal transplantation has been suggested as an alternative to total meniscectomy, which is now known to lead to long-term osteoarthritic degeneration of the knee joint. To evaluate the success of meniscal transplantation, we divided 28 sheep knees into 4 groups: total meniscectomy, allograft, autograft, and control. After a mean postoperative time of 21.4 months, we radiographed the excised knee joints in a loaded state and graded the radiographs for osteoarthritic changes. The knees with meniscectomies, allografts, and autografts showed significantly more degenerative changes than the control knees. However, there were no statistically significant differences between these three groups. The results of this study suggest that meniscal allograft transplantation does not protect the knee against degenerative changes.