The association of intrathecal immunoglobulin synthesis and cortical lesions predicts disease activity in clinically isolated syndrome and early relapsing–remitting multiple sclerosis

2011 ◽  
Vol 18 (2) ◽  
pp. 174-180 ◽  
Author(s):  
Massimiliano Calabrese ◽  
Lisa Federle ◽  
Valentina Bernardi ◽  
Francesca Rinaldi ◽  
Alice Favaretto ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Primary Role ◽  
Cortical Lesions ◽  
Intrathecal Synthesis ◽  
Immunoglobulin Synthesis ◽  
Humoral Immune ◽  
Relapsing Remitting ◽  
In Cis ◽  
Ig Synthesis

Background: The intrathecal production of immunoglobulin (Ig) is a major biological feature of multiple sclerosis (MS), and immunopathological studies have suggested a primary role of the humoral immune response in causing irreversible brain damage. Objective: To evaluate whether, in the early phases of MS, intrathecal Ig synthesis correlates with the presence of cortical lesions (CLs), and if their association could predict the clinical course of the disease. Methods: Eighty-six patients presenting with symptoms and signs suggestive of MS underwent a diagnostic work-up that included magnetic resonance imaging and cerebrospinal fluid examination. The risk ratios (RR) for conversion to MS and for a new disease activity were calculated. Results: Patients with clinically isolated syndromes (CIS) having CLs and intrathecal synthesis of Ig had the highest risk of conversion to MS (RR = 3.4; Wald 95% CI = 1.7–7.0, p < 0.001) whereas CIS patients without CLs and intrathecal synthesis of Ig had the lowest risk of conversion to MS (RR = 0.1, Wald 95% CI = 0.02–0.7, p < 0.001). The highest risk of having disease-related activity during the follow-up was observed in CIS and relapsing–remitting MS patients showing CLs and intrathecal Ig synthesis (RR = 2.1; Wald 95% CI = 1.5–3.1, p < 0.001) while the lowest in CIS and relapsing–remitting MS patients without CLs and intrathecal Ig synthesis (RR = 0.3; Wald 95% CI = 0.1–0.7, p < 0.001). Conclusion: We observed that the association of intrathecal immunoglobulin synthesis and CLs was highly predictive of an earlier CIS conversion to MS as well as of a higher disease activity.

Chlamydia pneumoniae in multiple sclerosis: humoral immune responses in serum and cerebrospinal fluid and correlation with disease activity marker

2001 ◽  
Vol 7 (1) ◽  
pp. 13-18 ◽  
Author(s):  
D Krametter ◽  
G Niederwieser ◽  
A Berghold ◽  
G Birnbaum ◽  
S Strasser-Fuchs ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Immune Responses ◽  
Disease Activity ◽  
Chlamydia Pneumoniae ◽  
Neurological Diseases ◽  
Intrathecal Synthesis ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Specific Igg

Humoral immune responses to Chlamydia pneumoniae (C. pneumoniae) were studied in paired sera and cerebrospinal fluid (CSF) of patients with definite multiple sclerosis (MS) and other inflammatory and non-inflammatory neurological diseases. Seropositivity was not significantly different between these groups. However, C. pneumoniae-specific IgG titers were significantly higher in CSF of MS than in controls. Sixteen out of 52 seropositive MS patients (30.8%) showed intrathecal synthesis of C. pneumoniae-specific IgG but only one of 43 seropositive controls (2.3%). In MS, this was strongly associated with intrathecal synthesis of polyclonal IgG in 13/16 patients. However, these elevated C. pneumoniae antibody titers in CSF did not significantly correlate with disease duration, disease course, clinical or MRI disease activity, disability or presence of oligoclonal IgG in MS.

scholarly journals Discontinuation and dose reduction of rituximab in relapsing–remitting multiple sclerosis

2021 ◽  
Author(s):  
Malin Boremalm ◽  
Peter Sundström ◽  
Jonatan Salzer
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Dose Reduction ◽  
Inflammatory Disease ◽  
University Hospital ◽  
Full Dose ◽  
Reduced Dose ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Abstract Background Rituximab is safe and effective for treating relapsing–remitting multiple sclerosis (RRMS) according to phase II and observational studies. There are limited data on disease activity after discontinuation and dose reduction. The objective of this study was to evaluate the effects on inflammatory disease activity after discontinuation or dose reduction of rituximab in patients with RRMS or clinically isolated syndrome (CIS). Methods In this retrospective observational study, we included all RRMS and CIS patients ever treated with rituximab at the University Hospital of Umeå who had either; (1) discontinued treatment at any time or (2) reduced the dose to a mean of < 1000 mg yearly. The patients served as their own controls by contributing patient years on full dose, reduced dose, and off treatment. Results A total of 225 patients treated with mean (SD) 6256 (2456) mg rituximab during mean (SD) 6.5 (2.0) years were included. There were no differences regarding the annualized relapse rates during full dose versus reduced dose or off treatment (0.02 versus < 0.01 and 0.02, p = 0.09), neither regarding proportion MRI scans with new or enlarged T2 lesions (0.03 versus 0.01 and 0.03, p = 0.37) or contrast-enhancing lesions (< 0.01 versus 0 and 0.02, p = 0.22). Conclusions This study indicates that rituximab has long-term effects on inflammatory disease activity and that disease reactivation is rare in MS patients who discontinued treatment for any reason. It also suggests that treatment with low-dose rituximab (< 1000 mg yearly) is sufficient to maintain suppression of inflammatory disease activity in patients with stable disease.

scholarly journals HIV infection and multiple sclerosis: a case with unexpected “no evidence of disease activity” status

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199957
Author(s):  
Fernando Labella ◽  
Fernando Acebrón ◽  
María del Carmen Blanco-Valero ◽  
Alba Rodrígez-Martín ◽  
Ángela Monterde Ortega ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Hiv Infection ◽  
Disease Activity ◽  
Demyelinating Disease ◽  
Clinical Course ◽  
Disease Modifying Drugs ◽  
Immunodeficiency Virus ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Disease Modifying

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system whose etiology remains unclear. It has been suggested that MS can be triggered by certain viruses; however, human immunodeficiency virus (HIV) infection is associated with reduced incidence of MS. We present the case of a young patient diagnosed with active relapsing-remitting MS whose clinical course substantially improved following HIV infection and treatment. The patient achieved no evidence of disease activity status without any disease-modifying drugs. Both HIV-induced immunosuppression and antiretroviral therapy may have attenuated the clinical course in this patient.

Heterogeneous pathological processes account for thalamic degeneration in multiple sclerosis: Insights from 7 T imaging

2017 ◽  
Vol 24 (11) ◽  
pp. 1433-1444 ◽  
Author(s):  
Céline Louapre ◽  
Sindhuja T Govindarajan ◽  
Costanza Giannì ◽  
Nancy Madigan ◽  
Jacob A Sloane ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Thalamic Lesion ◽  
Cortical Lesions ◽  
Focal Lesions ◽  
Thalamic Degeneration ◽  
Relapsing Remitting ◽  
Thalamic Lesions ◽  
Magnetic Resonance Imaging Mri

Background: Thalamic degeneration impacts multiple sclerosis (MS) prognosis. Objective: To investigate heterogeneous thalamic pathology, its correlation with white matter (WM), cortical lesions and thickness, and as function of distance from cerebrospinal fluid (CSF). Methods: In 41 MS subjects and 17 controls, using 3 and 7 T imaging, we tested for (1) differences in thalamic volume and quantitative T2* (q-T2*) (2) globally and (3) within concentric bands originating from the CSF/thalamus interface; (4) the relation between thalamic, cortical, and WM metrics; and (5) the contribution of magnetic resonance imaging (MRI) metrics to clinical scores. We also assessed MS thalamic lesion distribution as a function of distance from CSF. Results: Thalamic lesions were mainly located next to the ventricles. Thalamic volume was decreased in MS versus controls ( p < 10−2); global q-T2* was longer in secondary progressive multiple sclerosis (SPMS) only ( p < 10−2), indicating myelin and/or iron loss. Thalamic atrophy and longer q-T2* correlated with WM lesion volume ( p < 0.01). In relapsing-remitting MS, q-T2* thalamic abnormalities were located next to the WM ( p < 0.01 (uncorrected), p = 0.09 (corrected)), while they were homogeneously distributed in SPMS. Cortical MRI metrics were the strongest predictors of clinical outcome. Conclusion: Heterogeneous pathological processes affect the thalamus in MS. While focal lesions are likely mainly driven by CSF-mediated factors, overall thalamic degeneration develops in association with WM lesions.

scholarly journals Nine-year follow up after hematopoietic stem cell transplantation in five multiple sclerosis patients

2019 ◽  
Vol 77 (8) ◽  
pp. 531-535 ◽  
Author(s):  
Elizabeth R. Comini-Frota ◽  
Bruna C. C. Marques ◽  
Caio Torres ◽  
Karoline M. S. Cohen ◽  
Eduardo Carvalho Miranda
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Disease Activity ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Disease Onset ◽  
Hematopoietic Stem ◽  
Relapsing Remitting

ABSTRACT Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system. Its treatment has focused on inflammation control as early as possible to avoid disability. Autologous hematopoietic stem cell transplantation (AHSCT) has been used for treating MS since 1996, with recent decisive results regarding benefits in long-term efficacy. Five patients followed up at an MS center in Belo Horizonte, Brazil, who had relapsing-remitting MS with high disease activity, underwent AHSCT between 2009 and 2011. They were evaluated clinically, with magnetic resonance imaging, and by the EDSS every six months after transplantation, up to July 2018. The patients were four women and one man, with ages ranging from 25-50 years, and time since disease onset ranging from 4-17 years at the time of the procedure. Four patients improved, one patient was stabilized, and all patients were free of disease activity after 5-9 years. Through improving patient selection and decreasing the time from disease onset, AHSCT could stop epitope spreading and disease progression. Despite multiple other therapeutic choices being approved for relapsing-remitting MS, AHSCT continues to be a treatment to consider for aggressive MS disease.

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