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316: Chlamydia pneumoniae infection in patients with multiple sclerosis
Abstracts / Journal of Clinical Neuroscience 14 (2007) 1009–1040
Methods: We used individual patient data from the placebo arm of the European Lubeluzole Trial (part of the Virtual International Stroke Trials Archive). Survival analysis techniques were used to describe the temporal profile of cardiac mortality after stroke. Likely prognostic determinants were assessed with Cox regression. Associations are presented as hazard ratios (HR) with 95% confidence intervals. Results: A total of 846 ischemic stroke patients were studied, including 388 with symptomatic ischaemic heart disease and 250 with cardiac failure. Of the 184 deaths in the three month follow up period, 36 (19.6%) were attributable to cardiac causes, second only to the 79 (42.9%) who died from neurological causes related to their stroke. Risk of cardiac death was highest at study entry and then declined gradually. After day 14, deaths from cardiac causes were more frequent than neurological deaths. In a multivariate model, factors strongly associated with cardiac mortality included diabetes (HR 3.9 [1.9, 7.7], p < 0.001), cardiac failure (HR 3.1 [1.5, 6.4], p = 0.002), previous myocardial infarction (HR 2.4 [1.2, 4.7], p = 0.010), age (HR 1.6 per 10 years [1.1, 2.3], p = 0.013), and greater stroke severity (HR 1.04 per unit decrease in European Stroke Scale [1.02, 1.06], p < 0.001). Conclusion: Cardiac death is common in the first three months after stroke. Patients at highest risk of death are identifiable and may benefit from more aggressive investigation, monitoring or treatment to improve survival.
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and IgG and IgA antibodies using a commercial ELISA. All ELISA methods were semiquantitative. MRI scans with gadolinium were performed monthly examining for new T1-weighted MRI enhancing lesions, new and enlarging T2-weighted MRI lesions. The Mann–Whitney U test was used for analysis. 32.3% of MS patients, 24.3% OND controls and 21.8% healthy controls demonstrated serum immune complexes. Accounting for covariates the odds ratio for MS patients over healthy individuals was 3.0 (95% CI 1.82 to 4.94; p < 0.0001) although it was lower for incident MS patients (OR 2.17; 95% CI 1.02 to 4.61; p = 0.044). There were 41 new T1-weighted MRI enhancing lesions in the placebo group (n = 5) versus 19 in the treated group (n = 6: p = 0.072). There were 33 new or enlarging T2weighted MRI lesions in the placebo group compared to 20 in the Azithromycin group (p = 0.093). There were no significant differences in serological parameters of CP infection between groups. Infection with C. pneumoniae is more frequent in MS patients than the healthy population.The lower rate amongst incident MS patients may reflect increasing ‘‘susceptibility’’ as the disease progresses. Azithromycin treatment may reduce the number of new lesions in MS patients although this does not appear to be via suppression of CP infection. doi:10.1016/j.jocn.2007.02.022
doi:10.1016/j.jocn.2007.02.021
316: Chlamydia pneumoniae infection in patients with multiple sclerosis John D.E. Parratt a, Jonathon O’Riordan b, Robert J. Swingler b; a University of Sydney; b University of Dundee, United Kingdom The frequency of Chlamydia pneumoniae (CP) infection and the pathogenic relevance of the bacteria in patients with multiple sclerosis (MS) is unclear.We sought to clarify the rate of systemic infection in MS patients and examine whether modulating infection with antibiotics affects demyelination clinically. 155 MS patients, 70 neurological (OND) and 499 healthy controls were examined for CP specific serum immune complexes in a blinded, case-control study. An in-house ELISA sandwich technique was used. Multivariate, binary logistic regression was used to account for cohorts (including incident (n = 49) and prevalent (n = 107) MS), sex, age, area of residence and deprivation status. 11 infected MS patients were examined over a 6 month period in a double-blinded placebo controlled trial of Azithromycin 500mg thrice weekly. Blood samples were taken two weekly and analysed for CP specific immune complexes and antigen using in-house ELISA methods
317: Developing strategies to manage neutralising antibodies – preliminary results from the RENeu study and some individual case reports Suzanne J. Hodgkinson a, Les Sedal a, Mark Paine a, Stan Seijka a, Helmut Butzkueven a, David Booth a, Fiona Mackay a, Aaron Tabensky b; a Liverpool Hospital; b Biogen Idec, Sydney There are currently no clinical guidelines for management of interferon-beta (IFN) treated patients who develop neutralising antibodies (NAbs) to their IFN therapy. The RENeu study (Recovery of IFN-beta Efficacy in RRMS with Neutralising IFN-beta Antibodies and Reduced Bioactivity) tests the hypothesis that patients who develop persistent NAbs and are unresponsive to IFN as measured by MxA mRNA can (a) become NAb negative if their IFN therapy is ceased and their MS is managed by monthly pulsed methylprednisolone treatment (500 mg/day for 3 days) for up to 12 months, and (b) become responsive to IFN if they are reinitiated on the least immunogenic IFN i.e. AVONEX. The RENeu study will also assess the clinical efficacy and safety of this treatment regimen over 2 years. We report on preliminary results for the first patients enrolled in RENeu as well as some results in individual patients not eligible for this trial. Six patients (of 20 planned for RENeu) have been treated with monthly
Methods: We used individual patient data from the placebo arm of the European Lubeluzole Trial (part of the Virtual International Stroke Trials Archive). Survival analysis techniques were used to describe the temporal profile of cardiac mortality after stroke. Likely prognostic determinants were assessed with Cox regression. Associations are presented as hazard ratios (HR) with 95% confidence intervals. Results: A total of 846 ischemic stroke patients were studied, including 388 with symptomatic ischaemic heart disease and 250 with cardiac failure. Of the 184 deaths in the three month follow up period, 36 (19.6%) were attributable to cardiac causes, second only to the 79 (42.9%) who died from neurological causes related to their stroke. Risk of cardiac death was highest at study entry and then declined gradually. After day 14, deaths from cardiac causes were more frequent than neurological deaths. In a multivariate model, factors strongly associated with cardiac mortality included diabetes (HR 3.9 [1.9, 7.7], p < 0.001), cardiac failure (HR 3.1 [1.5, 6.4], p = 0.002), previous myocardial infarction (HR 2.4 [1.2, 4.7], p = 0.010), age (HR 1.6 per 10 years [1.1, 2.3], p = 0.013), and greater stroke severity (HR 1.04 per unit decrease in European Stroke Scale [1.02, 1.06], p < 0.001). Conclusion: Cardiac death is common in the first three months after stroke. Patients at highest risk of death are identifiable and may benefit from more aggressive investigation, monitoring or treatment to improve survival.
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and IgG and IgA antibodies using a commercial ELISA. All ELISA methods were semiquantitative. MRI scans with gadolinium were performed monthly examining for new T1-weighted MRI enhancing lesions, new and enlarging T2-weighted MRI lesions. The Mann–Whitney U test was used for analysis. 32.3% of MS patients, 24.3% OND controls and 21.8% healthy controls demonstrated serum immune complexes. Accounting for covariates the odds ratio for MS patients over healthy individuals was 3.0 (95% CI 1.82 to 4.94; p < 0.0001) although it was lower for incident MS patients (OR 2.17; 95% CI 1.02 to 4.61; p = 0.044). There were 41 new T1-weighted MRI enhancing lesions in the placebo group (n = 5) versus 19 in the treated group (n = 6: p = 0.072). There were 33 new or enlarging T2weighted MRI lesions in the placebo group compared to 20 in the Azithromycin group (p = 0.093). There were no significant differences in serological parameters of CP infection between groups. Infection with C. pneumoniae is more frequent in MS patients than the healthy population.The lower rate amongst incident MS patients may reflect increasing ‘‘susceptibility’’ as the disease progresses. Azithromycin treatment may reduce the number of new lesions in MS patients although this does not appear to be via suppression of CP infection. doi:10.1016/j.jocn.2007.02.022
doi:10.1016/j.jocn.2007.02.021
316: Chlamydia pneumoniae infection in patients with multiple sclerosis John D.E. Parratt a, Jonathon O’Riordan b, Robert J. Swingler b; a University of Sydney; b University of Dundee, United Kingdom The frequency of Chlamydia pneumoniae (CP) infection and the pathogenic relevance of the bacteria in patients with multiple sclerosis (MS) is unclear.We sought to clarify the rate of systemic infection in MS patients and examine whether modulating infection with antibiotics affects demyelination clinically. 155 MS patients, 70 neurological (OND) and 499 healthy controls were examined for CP specific serum immune complexes in a blinded, case-control study. An in-house ELISA sandwich technique was used. Multivariate, binary logistic regression was used to account for cohorts (including incident (n = 49) and prevalent (n = 107) MS), sex, age, area of residence and deprivation status. 11 infected MS patients were examined over a 6 month period in a double-blinded placebo controlled trial of Azithromycin 500mg thrice weekly. Blood samples were taken two weekly and analysed for CP specific immune complexes and antigen using in-house ELISA methods
317: Developing strategies to manage neutralising antibodies – preliminary results from the RENeu study and some individual case reports Suzanne J. Hodgkinson a, Les Sedal a, Mark Paine a, Stan Seijka a, Helmut Butzkueven a, David Booth a, Fiona Mackay a, Aaron Tabensky b; a Liverpool Hospital; b Biogen Idec, Sydney There are currently no clinical guidelines for management of interferon-beta (IFN) treated patients who develop neutralising antibodies (NAbs) to their IFN therapy. The RENeu study (Recovery of IFN-beta Efficacy in RRMS with Neutralising IFN-beta Antibodies and Reduced Bioactivity) tests the hypothesis that patients who develop persistent NAbs and are unresponsive to IFN as measured by MxA mRNA can (a) become NAb negative if their IFN therapy is ceased and their MS is managed by monthly pulsed methylprednisolone treatment (500 mg/day for 3 days) for up to 12 months, and (b) become responsive to IFN if they are reinitiated on the least immunogenic IFN i.e. AVONEX. The RENeu study will also assess the clinical efficacy and safety of this treatment regimen over 2 years. We report on preliminary results for the first patients enrolled in RENeu as well as some results in individual patients not eligible for this trial. Six patients (of 20 planned for RENeu) have been treated with monthly