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FP17-TU-04 CSF oligoclonal band as a marker for prognosis in multiple sclerosis
S84
19th World Congress of Neurology, Free Paper Abstracts / Journal of the Neurological Sciences 285 S1 (2009) S57–S154
FP17-TU-04 CSF oligoclonal band as a marker for prognosis in multiple sclerosis S. Demirkaya1 , M. Terzi2 , G. Genc¸ 1 , T. Kasık ¸ cı ¸ 1 , Z. Odabası ¸ 1. 1 Neurology, Gulhane, Medical Faculty, Ankara, Turkey; 2 Neurology, 19 Mayıs University, Samsun, Turkey Purpose: The diagnosis of multiple sclerosis (MS) is based on neurologic history, findings on examination, and exclusion of other disorders. The single most consistent laboratory abnormality in patients with MS except magnetic resonance imaging is increased oligoclonal immunoglobulins in cerebrospinal fluid (CSF). We investigated the association between CSF OCBs and clinical MS severity. Method: We report a retrospective and matched prospective comparison of the clinical and laboratory features of patients with clinical definite relapsing remitting MS with and without intrathecal synthesis of oligoclonal IgG. From the 113 patients, had preserved polyacrylamide gels at the time of review. We examined the relationship between OCB and age, sex, age at onset, disease duration, EDSS, evoked potentials (VEP, SEP, BAEP). Results: 46 patients were identified with apparent OCB positive and 67 patients were identified with apparent OCB negative clinically definite multiple sclerosis. The patients without OCB, at disease onset, had significantly higher frequency of visual disturbances and less pyramidal involvement than those with OCB. The spinal lesions in OCB negative patients was significantly lower than OCB positive patients. The number of T2 lesions in brain MRI was higher in patients with OCB positive. OCB positive patients had more initial polysymptomatic event than OCB negative patients. There was no statistical association between relapse rate, EDSS, disease duration and OCB in CSF. OCB positive patients had more tibial SEP abnormalities than OCB negative patients. Conclusions: OCB negative clinically definite multiple sclerosis seems to have a relatively benign prognosis. This is consistent with a secondary but nonetheless contributory role in disease process for intrathecally synthesised immunoglobulins. Absence of cerebrospinal fluid oligoclonal bands is associated with delayed disability progression in relapsing-remitting MS patients. FP17-TU-05 Screening for rheumatic diseases in the MS clinic: fulfilling the diagnostic criteria? M. Rolinski1 , M.C. Nimmo2 , A. Traboulsee3 . 1 School of Medicine, The University of Oxford, Oxford, United Kingdom; 2 Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, Canada; 3 Division of Neurology, The University of British Columbia, Vancouver, Canada Purpose: A number of rheumatic diseases can present with neurologic symptoms in a similar way to MS. In an attempt to exclude these conditions, thus fulfilling the McDonald diagnostic criteria, many centers routinely use laboratory tests as a screening tool. We aimed to investigate the utility of these tests in the context of a MS clinic. Method: We completed a retrospective study of 230 patients referred over a five year period with the diagnosis of possible MS. The results of screening tests for ANA, anti-ENA, ANCA, complement C3 and C4, rheumatoid factor, anti-dsDNA and vitamin B12 were correlated with the diagnosis at the end of the follow-up period. History of symptoms consistent with a rheumatic disorder was also recorded. Results: The diagnosis of a rheumatic disease was made in three (1.3%) of the patients in the cohort. Whilst all of these patients had at least one positive screening test result, 6.5% and 5.3% of patients meeting the diagnostic criteria for probable or definite MS also tested positive for ANA and anti-ENA, respectively. All three patients with a diagnosis of a rheumatic disease had features not
usually associated with MS, and two of these patients had features of a rheumatic disease at presentation. Conclusion: With the high incidence of positive autoantibody results in MS patients and the low frequency of rheumatic diagnoses being made in patients presenting with neurologic symptoms suspicious for MS, the routine screening of all patients presenting to a MS clinic lacks the specificity to identify non MS cases. Autoimmune screening is recommended only for patients with an atypical presentation or additional symptoms suspicious for rheumatic disease. FP17-TU-06 Th17, an effector T lymphocyte subset associated with multiple sclerosis (MS) relapses: antigen specificity, cytokine production, and sensitivity to interferon (IFN)-b L. Durelli1 , S. Rolla2 , L. Conti2 , M. Clerico1 , G. Contessa1 , P. Ripellino1 , D. La Puma1 , E. Viglietta1 , A. Uccelli3 , M. Zaffaroni4 , P. Cavalla5 , L. Rinaldi6 , C. Comi7 , F. Novelli2 . 1 Dept. of Clinical and Biological Sciences, San Luigi Gonzaga University School of Medicine, Orbassano, Italy; 2 C.E.R.M.S., Ospedale Universitario S. Giovanni Battista, Torino, Italy; 3 Clinica Neurologica II, Ospedale San Martino, Genova, Italy; 4 Divisione di Neurologia, Ospedale Civile di Gallarate, Gallarate, Italy; 5 Clinica Neurologica, Ospedale Universitario S. Giovanni Battista, Torino, Italy; 6 Divisione di Neurologia, Facolt` a di Medicina e Chirurgia, Universit` a di Padova, Padova, Italy; 7 Divisione di Neurologia, Facolt` a di Medicina e Chirurgia, Universit` a del Piemonte Orientale, Novara, Italy Purpose: Longitudinal study of the Th17/Th1 balance in active (i.e., with clinical signs of disease activity) or inactive MS (i.e., without clinical or MRI signs of disease activity). Method: Healthy subjects (HS, n = 22). Active MS patients (AMS, n = 30). Inactive MS patients (IMS, n = 32). Follow-up (6–18 months) during different phases of disease activity. ELISPOT assessment of IL-17-producing cells from PBMC stimulated with myelin basic protein (MBP, 40mg/ml) or with PPD. FACS analysis of activated PBMC and stained with anti-IFN-aR1 or anti-CD45RO and intracellularly using anti-IL-17, anti-IL-22, anti-IFN-g, and antiCD4 or CD8 mAbs. Cell cycle and apoptosis analysis on anti-CD3 re-stimulated cells treated with or without IFN-b-1a (100 U/ml) for 24–72 h and either incubated with RNase A and propidium iodide or with Annexin V/7-Amino-Actinomycin D (7-AAD). Results: Th17 decreased in patients whose disease status changed from AMS to IMS but remained stable in IMS patients whose disease status did not change. In patients who changed from AMS to IMS or from IMS to AMS several times Th17 were always higher in AMS, lower or undetectable in IMS, and increased again during a subsequent relapse. Th1 fluctuated randomly during the changes of disease activity. IL-22+ T CD4+ cells were low in HS and IMS and increased in AMS. About 80% of T CD4+ IL-17+ cells were also IL-22-producing. T CD4+ IL-17+ IL-22+ cells were increased in AMS while T CD4+ IL-17+ IL-22− were unchanged. IL-17-producing cells detected in MBP-stimulated PBMC were very low in HS, whereas it was significantly increased in AMS. IFN-b inhibits Th17 but not Th1 in a dose-dependent manner. Cell cycle analysis and annexin V and 7-AAD double staining showed that IFN-b increased early apoptotic cells. Conclusion: An expansion of peripheral MBP-specific, IL-22producing Th17, but not of Th1, is associated with disease activity in MS. Th17, but not Th1, were sensitive to the in vitro apoptotic effect of IFN-b.
19th World Congress of Neurology, Free Paper Abstracts / Journal of the Neurological Sciences 285 S1 (2009) S57–S154
FP17-TU-04 CSF oligoclonal band as a marker for prognosis in multiple sclerosis S. Demirkaya1 , M. Terzi2 , G. Genc¸ 1 , T. Kasık ¸ cı ¸ 1 , Z. Odabası ¸ 1. 1 Neurology, Gulhane, Medical Faculty, Ankara, Turkey; 2 Neurology, 19 Mayıs University, Samsun, Turkey Purpose: The diagnosis of multiple sclerosis (MS) is based on neurologic history, findings on examination, and exclusion of other disorders. The single most consistent laboratory abnormality in patients with MS except magnetic resonance imaging is increased oligoclonal immunoglobulins in cerebrospinal fluid (CSF). We investigated the association between CSF OCBs and clinical MS severity. Method: We report a retrospective and matched prospective comparison of the clinical and laboratory features of patients with clinical definite relapsing remitting MS with and without intrathecal synthesis of oligoclonal IgG. From the 113 patients, had preserved polyacrylamide gels at the time of review. We examined the relationship between OCB and age, sex, age at onset, disease duration, EDSS, evoked potentials (VEP, SEP, BAEP). Results: 46 patients were identified with apparent OCB positive and 67 patients were identified with apparent OCB negative clinically definite multiple sclerosis. The patients without OCB, at disease onset, had significantly higher frequency of visual disturbances and less pyramidal involvement than those with OCB. The spinal lesions in OCB negative patients was significantly lower than OCB positive patients. The number of T2 lesions in brain MRI was higher in patients with OCB positive. OCB positive patients had more initial polysymptomatic event than OCB negative patients. There was no statistical association between relapse rate, EDSS, disease duration and OCB in CSF. OCB positive patients had more tibial SEP abnormalities than OCB negative patients. Conclusions: OCB negative clinically definite multiple sclerosis seems to have a relatively benign prognosis. This is consistent with a secondary but nonetheless contributory role in disease process for intrathecally synthesised immunoglobulins. Absence of cerebrospinal fluid oligoclonal bands is associated with delayed disability progression in relapsing-remitting MS patients. FP17-TU-05 Screening for rheumatic diseases in the MS clinic: fulfilling the diagnostic criteria? M. Rolinski1 , M.C. Nimmo2 , A. Traboulsee3 . 1 School of Medicine, The University of Oxford, Oxford, United Kingdom; 2 Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, Canada; 3 Division of Neurology, The University of British Columbia, Vancouver, Canada Purpose: A number of rheumatic diseases can present with neurologic symptoms in a similar way to MS. In an attempt to exclude these conditions, thus fulfilling the McDonald diagnostic criteria, many centers routinely use laboratory tests as a screening tool. We aimed to investigate the utility of these tests in the context of a MS clinic. Method: We completed a retrospective study of 230 patients referred over a five year period with the diagnosis of possible MS. The results of screening tests for ANA, anti-ENA, ANCA, complement C3 and C4, rheumatoid factor, anti-dsDNA and vitamin B12 were correlated with the diagnosis at the end of the follow-up period. History of symptoms consistent with a rheumatic disorder was also recorded. Results: The diagnosis of a rheumatic disease was made in three (1.3%) of the patients in the cohort. Whilst all of these patients had at least one positive screening test result, 6.5% and 5.3% of patients meeting the diagnostic criteria for probable or definite MS also tested positive for ANA and anti-ENA, respectively. All three patients with a diagnosis of a rheumatic disease had features not
usually associated with MS, and two of these patients had features of a rheumatic disease at presentation. Conclusion: With the high incidence of positive autoantibody results in MS patients and the low frequency of rheumatic diagnoses being made in patients presenting with neurologic symptoms suspicious for MS, the routine screening of all patients presenting to a MS clinic lacks the specificity to identify non MS cases. Autoimmune screening is recommended only for patients with an atypical presentation or additional symptoms suspicious for rheumatic disease. FP17-TU-06 Th17, an effector T lymphocyte subset associated with multiple sclerosis (MS) relapses: antigen specificity, cytokine production, and sensitivity to interferon (IFN)-b L. Durelli1 , S. Rolla2 , L. Conti2 , M. Clerico1 , G. Contessa1 , P. Ripellino1 , D. La Puma1 , E. Viglietta1 , A. Uccelli3 , M. Zaffaroni4 , P. Cavalla5 , L. Rinaldi6 , C. Comi7 , F. Novelli2 . 1 Dept. of Clinical and Biological Sciences, San Luigi Gonzaga University School of Medicine, Orbassano, Italy; 2 C.E.R.M.S., Ospedale Universitario S. Giovanni Battista, Torino, Italy; 3 Clinica Neurologica II, Ospedale San Martino, Genova, Italy; 4 Divisione di Neurologia, Ospedale Civile di Gallarate, Gallarate, Italy; 5 Clinica Neurologica, Ospedale Universitario S. Giovanni Battista, Torino, Italy; 6 Divisione di Neurologia, Facolt` a di Medicina e Chirurgia, Universit` a di Padova, Padova, Italy; 7 Divisione di Neurologia, Facolt` a di Medicina e Chirurgia, Universit` a del Piemonte Orientale, Novara, Italy Purpose: Longitudinal study of the Th17/Th1 balance in active (i.e., with clinical signs of disease activity) or inactive MS (i.e., without clinical or MRI signs of disease activity). Method: Healthy subjects (HS, n = 22). Active MS patients (AMS, n = 30). Inactive MS patients (IMS, n = 32). Follow-up (6–18 months) during different phases of disease activity. ELISPOT assessment of IL-17-producing cells from PBMC stimulated with myelin basic protein (MBP, 40mg/ml) or with PPD. FACS analysis of activated PBMC and stained with anti-IFN-aR1 or anti-CD45RO and intracellularly using anti-IL-17, anti-IL-22, anti-IFN-g, and antiCD4 or CD8 mAbs. Cell cycle and apoptosis analysis on anti-CD3 re-stimulated cells treated with or without IFN-b-1a (100 U/ml) for 24–72 h and either incubated with RNase A and propidium iodide or with Annexin V/7-Amino-Actinomycin D (7-AAD). Results: Th17 decreased in patients whose disease status changed from AMS to IMS but remained stable in IMS patients whose disease status did not change. In patients who changed from AMS to IMS or from IMS to AMS several times Th17 were always higher in AMS, lower or undetectable in IMS, and increased again during a subsequent relapse. Th1 fluctuated randomly during the changes of disease activity. IL-22+ T CD4+ cells were low in HS and IMS and increased in AMS. About 80% of T CD4+ IL-17+ cells were also IL-22-producing. T CD4+ IL-17+ IL-22+ cells were increased in AMS while T CD4+ IL-17+ IL-22− were unchanged. IL-17-producing cells detected in MBP-stimulated PBMC were very low in HS, whereas it was significantly increased in AMS. IFN-b inhibits Th17 but not Th1 in a dose-dependent manner. Cell cycle analysis and annexin V and 7-AAD double staining showed that IFN-b increased early apoptotic cells. Conclusion: An expansion of peripheral MBP-specific, IL-22producing Th17, but not of Th1, is associated with disease activity in MS. Th17, but not Th1, were sensitive to the in vitro apoptotic effect of IFN-b.