Radiological Disease Activity Research Articles

BG-12 Increases the Proportion of Patients Free of Clinical and Radiologic Disease Activity in Relapsing-Remitting Multiple Sclerosis: Findings from the DEFINE Study (PD5.005)

Objective: To evaluate the impact of BG-12 (dimethyl fumarate) on the proportion of patients with relapsing-remitting multiple sclerosis (RRMS) who were free of clinical or magnetic resonance imaging (MRI) disease activity in the Phase 3 DEFINE study. Background DEFINE was a 2-year randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of BG-12 in patients with RRMS. In DEFINE, BG-12 significantly reduced clinical relapses, disability progression, and MRI measures of disease activity. Design/Methods: Patients aged 18-55 years with a diagnosis of RRMS and an Expanded Disability Status Scale (EDSS) score of 0.0-5.0 were included in the study. Patients were randomly assigned 1:1:1 to placebo, BG-12 240 mg twice daily (BID) or three times daily (TID). In the current analysis, absence of disease activity over 2 years was analyzed as follows: clinical (no relapses or EDSS progression), radiologic (no new or newly enlarging T2 lesions and gadolinium-enhancing lesions), and overall (no clinical and radiologic disease activity). Analyses of disease-free measures were performed on the MRI cohort using a chi-square test and logistic regression model. Results: The analysis included 469 patients with MRI measures. The proportion of disease-free patients over 2 years was significantly higher in both BG-12 treatment groups versus placebo: clinical (BID 63% and TID 59% vs placebo 39%; P P P Conclusions: Findings from this subset analysis of DEFINE indicate that BG-12 demonstrated a significant treatment effect on clinical, radiologic, and overall disease-free activity compared with placebo over 2 years in patients with RRMS. Supported by: Biogen Idec Inc. Disclosure: Dr. Giovannoni has received personal compensation for activities with Bayer-Pharmaceuticals Corporation, Biogen Idec, Five Prime Therapeutics, Inc, Genzyme Corporation, Ironwood Pharmaceuticals, Merck Serono, Novartis, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals and Vertex Pharmaceuticals as a speaker, consultant and/or serving on data monitoring boards. Dr. Gold has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Merck Serono, Teva Neuroscience. Dr. Gold has received personal compensation in an editorial capacity for Therapeutic Advances in Neurological Disorders. Dr. Gold has received (royalty or license fee or contractual rights) payments from Biogen Idec. Dr. Gold has received research support from Bayer Pharmaceuticals Corporation, Biogen Idec, Merck Serono, Novartis and Teva Neuroscience. Dr. Kappos has received research support from Acorda Therapeutics, Actelion, Allozyne, BaroFold, Inc., Bayer Pharmaceuticals Corporation, Bayhill Therapeutics, Biogen Idec, Boehringer Ingelheim Pharmaceuticals, Inc, Elan Corporation, Genmab, GlaxoSmithKline, Inc., Glenmark Pharma, Merck Serono, MediciNova, Novartis, Sanofi-Aventis Pharmaceuticals, Santhera Pharmaceuticals, Shire, Roche Diagnostics, Teva Neuroscience, UCB Pharma, Pfizer Inc, Swiss MS Society, Swiss National Research Foundation, European Union, Gianni Rubatto Foundation, Novartis and Roche Research Foundations. Dr. Arnold has received personal compensation for activities with Bayer Healthcare, Biogen Idec, Genentech, Inc., NeuroRx Research, Roche Diagnostics Corporation, Schering, Serono, Inc., and Teva Neuroscience. Dr. Arnold Dr. Arnold has received research support from Bayer Healthcare, Biogen Idec, Genentech, Inc., NeuroRx Research, Roche Diagnostics Corporation, Schering, Serono, Inc., and Teva Neuroscience. Dr. Bar-Or has received personal compensation for activities with Aventis Pharmaceuticals, Bayhill Therapeutics, Biogen Idec, Berlex Laboratories, Eli Lilly & Company, Genentech, Inc., GlaxoSmithKline, Ono Pharmaceutical, Diogenix, Roche Diagnostics Corporation, Merck Serono, Novartis, Teva Neuroscience. Dr. Selmaj has received personal compensation for activities with Genzyme, Ono, and Biogen Idec. Dr. Zhang has received personal compensation for activities with Biogen Idec as an employee. Dr. Sheikh has received personal compensation for activities with Biogen Idec as an employee. Dr. Dawson has received personal compensation for activities with Biogen Idec Inc. as an employee.

Clinical and Radiological Disease Activity Is Associated with Accelerated Rates of Retinal Ganglion Cell Layer Degeneration in Multiple Sclerosis (S10.002)

Clinical and Radiological Disease Activity Is Associated with Accelerated Rates of Retinal Ganglion Cell Layer Degeneration in Multiple Sclerosis (S10.002)

The Sustained Disease Activity Free Status as a Measure of Therapeutic Response & the Long Term Impact of Immunomodulatory Treatment (PD5.001)

Objective: To examine the effects of Interferon beta (IFNb) and Glatiramer Acetate (GA) on sustained disease activity free (DAF) status. Background IFNb and GA provide similar levels of efficacy in patients with relapsing-remitting multiple sclerosis (RRMS). However, they have not been demonstrated to induce disease remission. The sustained DAF status is a novel concept and viable goal of therapy based on clinical and radiological measures. Design/Methods: DAF status was defined as no activity on clinical measures (relapses and change in EDSS),and radiological measures (gadolinium-enhancing lesions and new/enlarging T2 lesions on cranial MRI). We assessed the impact of IFNb and GA on the proportion of DAF patients based on individual and combined components. All patients were matched according to baseline characteristics and treatment exposure. Results: This is a retrospective, observational study of 245 naive and RRMS patients who received immunomodulators over 10 (9.77+-3.28) years of follow up. 41 (35%) of 117 patients taking IFNb and 46 (35.9%) of 128 taking GA were free of clinical disease activity ([OR]0.96, 95% CI 0.56-1.62; p=0.8). 73 (77.7%) of 94 and 86 (81.9%) of 105 patients receiving IFNb and GA, respectively, were free of radiological disease activity ([OR]0.76 95% CI 0.38-1.53; p=0.45). Freedom from combined activity was observed in 26 (28.3%) of 92 patients taking IFNb and 40 (37%) of 108 taking GA ([OR]0.67, 95% CI 0.36-1.21; p=0.18). Although no differences were found between group treatments, subgroups analysis demonstrated a greater proportion of patients free from clinical disease activity among those on >=5 years of GA therapy ([OR] 0.32, 95% CI 0.12-0.82; p Conclusions: Both IFNb and GA induced DAF status in patients with RRMS, sustained in the long term. DAF status could be an important measure of therapeutic response in MS, yet applicable to immunomodulators currently in use. Disclosure: Dr. Carra has received personal compensation for activities with Biogen Idec, Merck Serono, Bayer Schering, Novartis, and Teva Neuroscience. Dr. Rojas has nothing to disclose. Dr. Vrech has nothing to disclose. Dr. Lindembaum has nothing to disclose.

Sa1852 Impact of Medications on Radiologic Disease Activity and Bowel Damage in Crohn's Disease: A Prospective Longitudinal MRI Study

Sa1852 Impact of Medications on Radiologic Disease Activity and Bowel Damage in Crohn's Disease: A Prospective Longitudinal MRI Study

Clinical and Radiological Disease Reactivation After Cessation of Long-Term Therapy With Natalizumab

ABSTRACTNaitalizumab is a potent monoclonal antibody approved for the treatment of relapsing–remitting multiple sclerosis (MS); however, little is known about the course of disease after cessation of therapy. The few existing reports describe different courses of disease after treatment discontinuation. Here we report on four MS patients who experienced clear clinical and radiological reactivation of the disease several months after cessation of therapy with natalizumab (15–29 months). In all cases, there was almost no clinical or radiological disease activity during natalizumab therapy. Three patients experienced a severe clinical relapse between 3 and 9 months after therapy cessation. The fourth patient developed cerebral magnetic resonance imaging (MRI) activity showing multiple new gadolinium-enhanced lesions. Due to these observations, it is recommended to weigh up the risk of disease reactivation against the risk of progressive multifocal leukoencephalopathy.

Effect of natalizumab on clinical and radiological disease activity in a French cohort of patients with relapsing-remitting multiple sclerosis

"Disease activity free" in relapsing-remitting multiple sclerosis (RRMS) is a new concept introduced by the results of the AFFIRM study. Our objective was to analyze the clinical and radiological efficacy of natalizumab treatment in actual clinical practice and compare it with the post hoc analysis of the AFFIRM study. All patients with RRMS who began treatment with natalizumab at our two French MS centres between April 2007 and May 2008 were included and followed-up for at least 2 years. No measurable disease activity ("disease activity free") was defined as no activity on clinical measures (no relapses and no sustained disability progression) and radiological measures (no gadolinium-enhancing lesions and no new T2-hyperintense lesions on cerebral MRI). A total of 193 patients were included. Natalizumab was discontinued in 25.9% of cases before the completion of 2 years of treatment. In our cohort, we observed patients with more severe disease than in the AFFIRM study. The proportion of patients remaining free of clinical activity during 2 years of treatment was lower than in the AFFIRM study (37.8% vs. 64.3%). The proportion of patients remaining free of radiological activity during 2 years of treatment was higher than in the AFFIRM study (68.9% vs. 57.7%), while the proportion of patients remaining free of disease activity during 2 years of treatment was comparable to the AFFIRM study (33.3% vs. 36.7%). Natalizumab seems to be as effective in a real-life setting as in pivotal and post hoc studies. The confirmation of such benefits is important because of the progressive multifocal leukoencephalopathy risk.

Natalizumab and drug holiday in clinical practice: An observational study in very active relapsing remitting Multiple Sclerosis patients

In order to reduce the risk of progressive multifocal leucoencephalopathy when using natalizumab for more than 12 months, a 6-month drug holiday has been discussed. However, the consequences on short term disease activity have been poorly assessed. The aim of this study was to assess clinical and radiological disease activity within 6 months after stopping natalizumab in very active relapsing remitting Multiple Sclerosis (RRMS) patients. In 8 hospitals from Western France, we retrospectively collected clinical and MRI data from consecutive RRMS patients treated with natalizumab for at least 6 months, and who stopped the drug for various reasons except therapeutic failure. Patients didn't receive any other disease modifying treatment after discontinuing natalizumab. A total of 27 patients with very active RRMS before natalizumab start (mean annualized relapse rate of 2.3, MRI activity in 21 of 27 patients) were studied. Within 6 months after discontinuing natalizumab, 18 patients (67%) experienced clinical relapse and 3 additional patients had radiological activity, without clinical relapse. Four patients (15%) experienced a rebound activity, with severe relapse and 20 or more gadolinium enhancing lesions on MRI. Such observational data didn't support the concept of drug holiday when using natalizumab in very active RRMS.

Pulsed steroids followed by glatiramer acetate to prevent inflammatory activity after cessation of natalizumab therapy: a prospective, 6-month observational study

In this study, the tolerability and safety of treatment with pulsed steroids and glatiramer acetate and the occurrence of clinical and radiological activity after natalizumab (NTZ) cessation in multiple sclerosis (MS) patients were assessed. MS patients with NTZ were discontinued after 2years of treatment, or if adverse events or disease progressed during NTZ. They were offered as alternative treatment 1 g methylprednisolone per month during 3months followed by daily 20 mcg glatiramer acetate and were prospectively studied. Adverse events, occurrence of immune reconstitution inflammatory syndrome, clinical exacerbations, and gadolinium-enhancing lesions in MRI performed at 3 and 6months after NTZ cessation were recorded. EDSS change during follow-up was also recorded. A total of 18 MS patients entered the study and were followed up for a mean of 10months (range 6-18months). There were no significant adverse events. At month 3, no patient had clinical or radiological disease activity. At month 6, 16.6% of patients had had a relapse and 55.5% of patients showed gadolinium-enhancing lesions in the MRI. After 6months, 33.3% of patients had a further relapse. There was no IRIS, severe relapses, or significant difference between EDSS at NTZ discontinuation and after follow-up. The alternative treatment with monthly prednisolone followed by GA prevents the development of IRIS, but not the return to previous inflammatory activity, which occurs between 5 and 6months after NTZ withdrawal.

Estudio observacional sobre la efectividad y seguridad del natalizumab en el tratamiento de la esclerosis múltiple

To analyse the safety and effectiveness of natalizumab in the treatment of multiple sclerosis in a real clinical practice setting and according to the approved indications. All patients with multiple sclerosis treated with natalizumab in our centre were evaluated. The clinical and radiological disease activity during the first year of treatment was analyzed in patients who received at least 12 doses of the drug. The data regarding moderate and severe adverse events in the entire study sample was also evaluated. A total of 112 patients were included in the study, of which 110 had been previously treated with other drugs and 76 had received at least 12 doses of natalizumab. In this group, the annualized relapse rate was reduced by 89% compared to the preceding year and 80% of patients were free from relapses after one year of treatment. Nine percent of patients exhibited 3-month confirmed disability progression. At month 12, the mean number of gadolinium-enhancing lesions on brain MRI was decreased by 99% compared to the pre-treatment MRI. During the first year of treatment, 76% of patients remained free from clinical activity and 33% remained free from both clinical and radiological disease activity. Twenty-nine percent of patients had at least one moderate or severe adverse event, which led to treatment discontinuation in 6%. Four percent of patients experienced immediate hypersensitivity reactions. This study suggests that natalizumab is effective in reducing disease activity in patients with relapsing multiple sclerosis and inadequate response to other therapies, with a favorable risk-benefit ratio.

Natalizumab para la esclerosis múltiple remitente-recurrente

Introduction Natalizumab is a monoclonal antibody that inhibits leukocyte migration across the blood-brain barrier and has been approved for the treatment of relapsing-remitting multiple sclerosis. Objective To provide a review and update of the pharmacological and therapeutic characteristics of natalizumab, with special emphasis on the most recently published data on the efficacy, effectiveness and safety of this drug. Development Several randomized clinical trials in patients with relapsing forms of multiple sclerosis have demonstrated that natalizumab substantially reduces clinical and radiological disease activity. Post hoc analysis of phase III clinical trials and the results of post-approval observational studies indicate that natalizumab significantly increases the proportion of patients with complete clinical and radiological response and is effective in patients with highly active forms of multiple sclerosis and suboptimal response to other treatments. Like other monoclonal antibodies, natalizumab can cause hypersensitivity reactions, which are severe in 1% of patients. Other adverse effects are generally mild or infrequent. Nevertheless, several cases of progressive multifocal leukoencephalopathy have been detected in patients treated with natalizumab monotherapy. The risk of this severe complication seems to increase with the number of doses administered. Conclusion Natalizumab has a favorable risk-benefit ratio in the treatment of relapsing -remitting multiple sclerosis. However, because of the potential risk of progressive multifocal leukoencephalopathy, patients must be carefully selected and specific protocols must be followed during the drug's administration.

Additional benefit of procalcitonin to C‐reactive protein to assess disease activity and severity in Crohn’s disease

Serum procalcitonin level may reflect non-infectious inflammation. To assess the correlation of serum procalcitonin level with clinical, biological, endoscopic and radiological markers of disease activity in inflammatory bowel diseases (IBD), and to evaluate the additional diagnostic benefit of measuring serum procalcitonin level to that of C-reactive protein (CRP) for disease activity appraisal. We performed a prospective observational study. Spearman's rank correlation and receiver operating characteristic analysis were used to evaluate correlation and diagnostic accuracy respectively. In Crohn's disease (CD) (n = 30), serum procalcitonin level was strongly correlated with clinical, biological, endoscopic and radiological disease activity markers. In CD, the serum procalcitonin level >0.14 μg/L demonstrated a high accuracy for detecting severe disease (Sensitivity = 100%; Specificity = 96%; AUROC = 0.963; P = 0.0001). The diagnostic accuracy of the 'serum procalcitonin level-CRP strategy' (CRP >5 mg/L and serum procalcitonin level >0.05 μg/L) was significantly superior to that of CRP alone for diagnosing severe CD (AUROC = 0.783 vs. 0.674; P = 0.01). In ulcerative colitis (UC) (n = 27), serum procalcitonin level was correlated with CRP and with endoscopic and radiological disease activity markers. In CD, the serum procalcitonin level was correlated with all disease activity markers and a cut-off of 0.14 μg/L could distinguish severe forms of the disease. The 'serum procalcitonin level-CRP strategy' was superior to CRP alone for diagnosing active or severe CD.

Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity

Treatment of early relapsing-remitting multiple sclerosis with the lymphocyte-depleting humanized monoclonal antibody alemtuzumab (Campath [registered trade mark]) significantly reduced the risk of relapse and accumulation of disability compared with interferon β-1a in a phase 2 trial [Coles et al., (Alemtuzumab vs. interferon β-1a in early multiple sclerosis. N Engl J Med 2008; 359: 1786-801)]. Patients treated with alemtuzumab experienced an improvement in disability at 6 months that was sustained for at least 3 years. In contrast, those treated with interferon β-1a steadily accumulated disability. Here, by post hoc subgroup analyses of the CAMMS223 trial, we show that among participants with no clinical disease activity immediately before treatment, or any clinical or radiological disease activity on-trial, disability improved after alemtuzumab but not following interferon β-1a. This suggests that disability improvement after alemtuzumab is not solely attributable to its anti-inflammatory effect. So we hypothesized that lymphocytes, reconstituting after alemtuzumab, permit or promote brain repair. Here we show that after alemtuzumab, and only when specifically stimulated with myelin basic protein, peripheral blood mononuclear cell cultures produced increased concentrations of brain-derived neurotrophic factor, platelet-derived growth factor and ciliary neurotrophic factor. Analysis by reverse transcriptase polymerase chain reaction of cell separations showed that the increased production of ciliary neurotrophic factor and brain-derived neurotrophic factor after alemtuzumab is attributable to increased production by T cells. Media from these post-alemtuzumab peripheral blood mononuclear cell cultures promoted survival of rat neurones and increased axonal length in vitro, effects that were partially reversed by neutralizing antibodies against brain-derived nerve growth factor and ciliary neurotrophic factor. This conditioned media also enhanced oligodendrocyte precursor cell survival, maturation and myelination. Taken together, the clinical analyses and laboratory findings support the interpretation that improvement in disability after alemtuzumab may result, in part, from neuroprotection associated with increased lymphocytic delivery of neurotrophins to the central nervous system.

The effect of war stress on multiple sclerosis exacerbations and radiological disease activity

Objective The relationship between stressful life events and multiple sclerosis (MS) exacerbations or radiological disease activity is at best controversial. The aim of this study is to examine the relationship between exposure to war-related events incurred during the July 2006 Israeli–Lebanese war and clinical relapses and MRI disease activity among Lebanese MS patients. Methods We studied a group of 216 patients with clinically definite relapsing remitting MS (RRMS), on whom clinical data was available for the war period and for the preceding and following year(s). The number of relapses was determined during the war period and during similar periods over a 3-year span. All patients with brain MRI during the war period had their scans reviewed for evidence of disease activity as defined by the presence of gadolinium enhancing (Gd+) lesions. A group of patients with brain MRI performed outside the war period was used for comparison. Results The total number of relapses during the war period ( n = 23) was significantly higher than during non-war periods (mean = 8.4, SD = 0.86) ( p = 0.006). Of the 18 patients with brain MRI during the war, 5/7 with relapses and 1/11 without relapses had Gd+ lesions ( p = 0.013). More patients had Gd+ lesions during the war period (33%) compared to controls (13%) ( p = 0.075). Interpretation Our study shows that exposure to war-related events is likely to lead to an increase in both clinical relapses and MRI disease activity in patients with MS.

Getting the measure of multiple sclerosis

In this issue of The Lancet Neurology, Eva Havrdova and co-workers 1 Havrdova E Galetta S Hutchinson M et al. Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study. Lancet Neurol. 2009; (published online Feb 9.)https://doi.org/10.1016/S1474-4422(09)70021-3 Summary Full Text Full Text PDF Scopus (376) Google Scholar provide an interesting approach to the assessment of a treatment for multiple sclerosis by combining clinical and MRI outcomes in a measure of so-called disease freedom. As with other neurological disorders, development of outcome measures for multiple sclerosis that are meaningful to clinicians and patients over both short and long periods is difficult, because no single measure captures the disease complexity. Even the most widely used measure—the expanded disability status scale—is a composite score in some senses, but becomes a measure of ability to walk above a score of 5 on a 0–10 scale. The multiple sclerosis functional composite 2 Rudick RA Cutter G Reingold S The multiple sclerosis functional composite: a new clinical outcome measure for multiple sclerosis trials. Mult Scler. 2002; 8: 359-365 Crossref PubMed Scopus (160) Google Scholar and its successors are designed to measure the various domains of dysfunction but maintain the ability to detect changes between treatment groups. No widely accepted serum or CSF biomarkers of disease activity exist, and relapse rate—despite its potential variability—is the measure of disease activity used in most clinical trials for relapsing-remitting disease. Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) studyDisease remission might become an increasingly attainable goal in multiple sclerosis treatment with the use of newer, more effective therapies. Full-Text PDF

Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study

The efficacy of natalizumab on clinical and radiological measures in the phase III Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study has prompted the investigation of whether natalizumab can increase the proportion of patients with relapsing-remitting multiple sclerosis who do not have disease activity. Post-hoc analyses of data from the AFFIRM study were done to determine the effects of natalizumab compared with placebo on the proportion of patients who were free of disease activity over 2 years. Absence of disease activity was defined as no activity on clinical measures (no relapses and no sustained disability progression), radiological measures (no gadolinium-enhancing lesions and no new or enlarging T2-hyperintense lesions on cranial MRI), or a composite of the two. 383 (64%) of 596 patients taking natalizumab and 117 (39%) of 301 taking placebo were free of clinical disease activity (absolute difference 25.4%, 95% CI 18.7-32.1%, p<0.0001); 342 (58%) of 593 and 42 (14%) of 296 were free of radiological disease activity (43.5%, 37.9-49.1%, p<0.0001); and 220 (37%) of 600 and 22 (7%) of 304 were free of combined activity (29.5%, 24.7-34.3%, p<0.0001) over 2 years. The effect of natalizumab versus placebo was consistent across subgroups of patients with highly active or non-highly active disease at baseline. Disease remission might become an increasingly attainable goal in multiple sclerosis treatment with the use of newer, more effective therapies.

Circulating Dickkopf-1 and Radiological Progression in Patients with Early Rheumatoid Arthritis Treated with Etanercept

Dickkopf-1 (Dkk-1) regulates bone remodeling in animal models of inflammatory arthritis, but its role in patients with rheumatoid arthritis (RA) remains unclear. Baseline circulating Dkk-1 was measured in 113 patients with RA (< 3 yrs) who received etanercept (10 or 25 mg twice/week, n = 63) or methotrexate alone (n = 40) for 1 year. Progression was assessed by changes in radiological Sharp score. Increased Dkk-1 was associated with a higher risk of progression of bone erosion, independently of age, sex, baseline radiological damage, C-reactive protein, and disease activity in patients treated with etanercept. Dkk-1 may be an important mediator of bone erosion in patients with RA.

The relation of hand functions with radiological damage and disease activity in rheumatoid arthritis

The purpose of this study was to investigate specifically the correlation of hand functions determined by Duruoz hand index (DHI) with radiological findings and disease activity in rheumatoid arthritis (RA) patients. Forty-eight RA patients were evaluated with DHI questionnaire, disease activity score (DAS) 28 and modified Larsen scoring method. Correlation between DAS-28 and DHI was assessed in all the patients. Mean DHI scores were compared between patients in remission (DAS-28 < 2.6) and patients who have more or less disease activity (DAS-28 >or= 2.6). To exclude the probable conflicting effect of disease activity on hand functions, the correlation between radiological scores and DHI was investigated only in patients with remission. There was a positive correlation between DAS-28 and DHI in all patients group (r = 0.434, P < 0.002). No correlation between the radiological scores of any joint groups and DHI could be found in patients with remission. Hand functions seemed to be affected prominently from disease activity. Radiological scores demonstrating joint damage were not in relation with hand functions.

Tau, Phospho-Tau, and S-100B in the Cerebrospinal Fluid of Children With Multiple Sclerosis

Axonal injury and glial activation are an early neuropathologic event in adults with multiple sclerosis. To investigate whether markers of axonal injury and glial activation are already elevated in the cerebrospinal fluid of children with multiple sclerosis, we studied the cerebrospinal fluid of 25 children with multiple sclerosis and 67 controls for the presence of tau, phospho-tau, and S-100B proteins using specific enzyme-linked immunoabsorbent assays. In general, tau, phospho-tau, and S-100B protein levels did not differ significantly between groups. However, in a subgroup of nine children with multiple sclerosis, all of whom had prominent clinical symptoms at the time of lumbar puncture and radiologic disease activity, tau protein levels were significantly elevated when compared with other controls. These data indicate that axonal injury is not restricted to adult multiple sclerosis but can already occur in children with multiple sclerosis.

Anticorps anticytoplasme des polynucléaires chez les patients atteints de polyarthrite rhumatoïde : corrélations avec les caractéristiques cliniques, biologiques et radiologiques

Objectives. – To determine the prevalence and the associations of anti-neutrophil cytoplasmic antibodies (ANCA) and subtypes with clinical, biological and radiological findings in patients with rheumatoid arthritis (RA). Materials and methods. – This is a transversal study of 85 patients with RA (followed in Ibn-i Sina Hospital of School of Medicine, Ankara University) with disease duration of 8.7 ± 6.4 years. Besides clinical, biological and radiological disease activity parameters, ANCA and ANCA against myeloperoxidase (MPO) and proteinase 3 (PR3) were examined. Results. – The prevalence of ANCA, perinuclear ANCA (p-ANCA) and atypical ANCA (a-ANCA) were 18% (15/85 patients), 6% and 12%, respectively. Anti-MPO was found in six patients while anti-PR3 was not found. No significant association could be found between clinical, biological, and radiological disease activity assessments and ANCA (including indirect immunoflorescence subtypes). Similarly, ANCA were not associated with features suggestive of underlying vasculitis (noticed in 11/85 patients), and/or other extra-articular features. Conclusions. – Our results confirm that ANCA of various specificities (mainly a-ANCA) occur in a minority of RA. However, those ANCA were not associated with more severe RA, including the 6/85 patients positive for MPO (who were all free from vasculitis). The over-representation in RA sera of a-ANCA, as compared to p-ANCA, should be further studied.

Anti-neutrophil cytoplasmic antibodies in patients with rheumatoid arthritis: clinical, biological, and radiological correlations

Objectives. – To determine the prevalence and the associations of anti-neutrophil cytoplasmic antibodies (ANCA) and subtypes with clinical, biological, and radiological findings in patients with rheumatoid arthritis (RA). Materials and methods. – This is a transversal study of 85 patients with RA (followed in Ibn-i Sina Hospital, Ankara University School of Medicine) with disease duration of 8.7 ± 6.4 years. Besides clinical, biological, and radiological disease activity parameters, ANCA and ANCA against myeloperoxidase (MPO) and proteinase 3 (PR3) were examined. Results. – The prevalence of ANCA, perinuclear ANCA (p-ANCA) and atypical ANCA (a-ANCA) were 18% (15/85 patients), 6% and 12%, respectively. Anti-MPO was found in six patients while anti-PR3 was not found. No significant association could be found between clinical, biological, and radiological disease activity assessments and ANCA (including indirect immunoflorescence subtypes). Similarly, ANCA were not associated with features suggestive of underlying vasculitis (noticed in 11/85 patients), and/or other extra-articular features. Conclusions. – Our results confirm that ANCA of various specificities (mainly a-ANCA) occur in a minority of RA. However, those ANCA were not associated with more severe RA, including the 6/85 patients positive for MPO (who were all free from vasculitis). The over-representation in RA sera of a-ANCA, as compared to p-ANCA, should be further studied.