Cerebrospinal Fluid IgM and Oligoclonal IgG Bands in Multiple Sclerosis: A Meta-Analysis of Prevalence and Prognosis

The presence of intrathecal IgM synthesis (ITMS) has been associated with an aggressive multiple sclerosis (MS) clinical course. In the present systematic review, we aimed at assessing the prevalence of ITMS among different MS phenotypes. Moreover, we aimed at quantifying the risk of a second relapse in ITMS positive and oligoclonal IgG bands (OCGBs)-positive patients. We selected clinical studies reporting the ITMS prevalence assessed as oligoclonal IgM Bands (OCMBs), lipid-specific OCMBs (LS-OCMBs), and/or as an intrathecal IgM production > 0% (IgMLoc, Reiber formula). The overall prevalence of ITMS was higher in relapsing-remitting (RR) than clinically isolated syndrome (CIS) patients (40.1% versus 23.8%, p < 0.00001), while was in line with that detected in primary progressive MS (PPMS, 26.7%). Almost all patients (98%) with ITMS had also OCGBs. The risk of having a second relapse was higher in OCGBs positive patients (HR = 2.18, p = 0.007) but much higher in ITMS positive patients (HR = 3.62, p = 0.0005). This study revealed that the prevalence of ITMS is higher in RRMS patients. It suggests that the risk of having a second relapse, previously ascribed to OCGBs, may, to a certain extent, be related to the presence of intrathecal IgM.

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Oligoclonal IgG bands in the cerebrospinal fluid of portuguese patients with multiple sclerosis: negative results indicate benign disease

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2005000300001 ◽

2005 ◽

Vol 63 (2b) ◽

pp. 375-379 ◽

Cited By ~ 11

Author(s):

Maria José Sá ◽

Lucinda Sequeira ◽

Maria Edite Rio ◽

Edward J. Thompson

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Benign Disease ◽

Serum Samples ◽

Negative Results ◽

Significant Difference ◽

Relapsing Remitting ◽

The Mean ◽

Oligoclonal Igg ◽

Oligoclonal Igg Bands

We assessed the frequency of cerebrospinal fluid (CSF) restricted oligoclonal IgG bands (IgG-OCB) in Portuguese multiple sclerosis (MS) patients and its relationship with outcome. Paired CSF/serum samples of 406 patients with neurological disorders were submitted to isoelectric focusing with immunodetection of IgG. Ninety-two patients had definite MS; non-MS cases were assembled in groups inflammatory/infectious diseases (ID, n=141) and other/controls (OD, n=173). We found in the MS group: mean duration, 38.9 months; clinically isolated syndromes, 24%; relapsing/remitting course (RR), 65%; in RR patients the mean EDSS was 2.1 and the mean index of progression was 0.31. Positive patterns significantly predominated in MS (82.6%; ID, 40.4%; OD, 3.5%). The sensitivity and the specificity of positive IgG-OCB for MS diagnosis was 82.6% and 79.9%, respectively. The sole statistically significant difference in the MS group was the lower progression index observed in negative cases. We conclude that the frequency of positive IgG-OCB patterns in our MS patients fits most values reported in the literature, and that negative results indicate benign disease.

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Emotional outcomes in clinically isolated syndrome and early phase multiple sclerosis: a systematic review and meta-analysis

Journal of Psychosomatic Research ◽

10.1016/j.jpsychores.2019.109761 ◽

2019 ◽

Vol 124 ◽

pp. 109761 ◽

Cited By ~ 5

Author(s):

A. Rintala ◽

F. Matcham ◽

M. Radaelli ◽

G. Locafaro ◽

S. Simblett ◽

...

Keyword(s):

Multiple Sclerosis ◽

Systematic Review ◽

Early Phase ◽

Meta Analysis ◽

Clinically Isolated Syndrome ◽

Emotional Outcomes

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Comparative efficacy of disease-modifying therapies for patients with relapsing remitting multiple sclerosis: Systematic review and network meta-analysis

Multiple Sclerosis and Related Disorders ◽

10.1016/j.msard.2016.06.001 ◽

2016 ◽

Vol 9 ◽

pp. 23-30 ◽

Cited By ~ 59

Author(s):

Emer Fogarty ◽

Susanne Schmitz ◽

Niall Tubridy ◽

Cathal Walsh ◽

Michael Barry

Keyword(s):

Multiple Sclerosis ◽

Systematic Review ◽

Meta Analysis ◽

Comparative Efficacy ◽

Disease Modifying Therapies ◽

Relapsing Remitting ◽

Disease Modifying ◽

Remitting Multiple Sclerosis ◽

Relapsing Remitting Multiple Sclerosis

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Cerebrospinal Fluid Findings in 541 Patients With Clinically Isolated Syndrome and Multiple Sclerosis: A Monocentric Study

Frontiers in Immunology ◽

10.3389/fimmu.2021.675307 ◽

2021 ◽

Vol 12 ◽

Author(s):

Klaus Berek ◽

Gabriel Bsteh ◽

Michael Auer ◽

Franziska Di Pauli ◽

Anne Zinganell ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

White Blood Cells ◽

Clinically Isolated Syndrome ◽

The Novel ◽

Barrier Dysfunction ◽

Csf Pleocytosis ◽

Oligoclonal Igg ◽

Wbc Count ◽

Oligoclonal Igg Bands

BackgroundReports on typical routine cerebrospinal fluid (CSF) findings are outdated owing to novel reference limits (RL) and revised diagnostic criteria of Multiple Sclerosis (MS).ObjectiveTo assess routine CSF parameters in MS patients and the frequency of pathologic findings by applying novel RL.MethodsCSF white blood cells (WBC), CSF total protein (CSF-TP), CSF/serum albumin quotient (Qalb), intrathecal synthesis of immunoglobulins (Ig) A, M and G, oligoclonal IgG bands (OCB) were determined in patients with clinically isolated syndrome (CIS) and MS.ResultsOf 541 patients 54% showed CSF pleocytosis with a WBC count up to 40/μl. CSF cytology revealed lymphocytes, monocytes and neutrophils in 99%, 41% and 9% of patients. CSF-TP and Qalb were increased in 19% and 7% applying age-corrected RL as opposed to 34% and 26% with conventional RL. Quantitative intrathecal IgG, IgA and IgM synthesis were present in 65%, 14% and 21%; OCB in 95% of patients. WBC were higher in relapsing than progressive MS and predicted, together with monocytes, the conversion from CIS to clinically definite MS. Intrathecal IgG fraction was highest in secondary progressive MS.ConclusionsCSF profile in MS varies across disease courses. Blood-CSF-barrier dysfunction and intrathecal IgA/IgM synthesis are less frequent when the novel RL are applied.

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Leptomeningeal Enhancement in Multiple Sclerosis and Other Neurological Diseases: A Systematic Review and Meta-Analysis

10.1101/2021.12.15.472797 ◽

2021 ◽

Author(s):

Benjamin Victor Ineichen ◽

Charidimos Tsagkas ◽

Martina Absinta ◽

Daniel S Reich

Keyword(s):

Multiple Sclerosis ◽

Systematic Review ◽

Neurological Diseases ◽

Meta Analysis ◽

Mean Difference ◽

Clinical Settings ◽

Imaging Features ◽

Qualitative Synthesis ◽

Leptomeningeal Enhancement ◽

Relapsing Remitting

Background: The lack of systematic evidence on leptomeningeal enhancement (LME) on MRI in neurological diseases, including multiple sclerosis (MS), hampers its interpretation in clinical routine and research settings. Purpose: To perform a systematic review and meta-analysis of MRI LME in MS and other neurologi-cal diseases. Materials and Methods: In a comprehensive literature search in Medline, Scopus, and Embase, out of 2292 publications, 459 records assessing LME in neurological diseases were eligible for qualitative synthesis. Of these, 135 were included in a random effects model meta-analysis with subgroup analyses for MS. Results: Of eligible publications, 161 investigated LME in neoplastic neurological (n=2392), 91 in neuroinfectious (n=1890), and 75 in primary neuroinflammatory diseases (n=4038). The LME proportions for these disease classes were 0.47 [95%CI: 0.37 to 0.57], 0.59 [95%CI: 0.47 to 0.69], and 0.26 [95%CI: 0.20 to 0.35], respectively. In a subgroup analysis comprising 1605 MS cases, LME proportion was 0.30 [95%CI 0.21 to 0.42] with lower proportions in relapsing-remitting (0.19 [95%CI 0.13 to 0.27]) compared to progressive MS (0.39 [95%CI 0.30 to 0.49], p=0.002) and higher proportions in studies imaging at 7T (0.79 [95%CI 0.64 to 0.89]) compared to lower field strengths (0.21 [95%CI 0.15 to 0.29], p<0.001). LME in MS was associated with longer disease duration (mean difference 2.2 years [95%CI 0.2 to 4.2], p=0.03), higher Expanded Disability Status Scale (mean difference 0.6 points [95%CI 0.2 to 1.0], p=0.006), higher T1 (mean difference 1.6ml [95%CI 0.1 to 3.0], p=0.04) and T2 lesion load (mean difference 5.9ml [95%CI 3.2 to 8.6], p<0.001), and lower cortical volume (mean difference -21.3ml [95%CI -34.7 to -7.9], p=0.002). Conclusions: Our study provides high-grade evidence for the substantial presence of LME in MS and a comprehensive panel of other neurological diseases. Our data could facilitate differential diagnosis of LME in clinical settings. Additionally, our meta-analysis corroborates that LME is associ-ated with key clinical and imaging features of MS. PROSPERO No: CRD42021235026.

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Disease-modifying treatments and cognition in relapsing-remitting multiple sclerosis

Neurology ◽

10.1212/wnl.0000000000009522 ◽

2020 ◽

Vol 94 (22) ◽

pp. e2373-e2383 ◽

Cited By ~ 8

Author(s):

Nils C. Landmeyer ◽

Paul-Christian Bürkner ◽

Heinz Wiendl ◽

Tobias Ruck ◽

Hans-Peter Hartung ◽

...

Keyword(s):

Multiple Sclerosis ◽

Systematic Review ◽

Cognitive Impairment ◽

Test Performance ◽

Meta Analysis ◽

Cognitive Test ◽

Current Evidence ◽

Relapsing Remitting ◽

Disease Modifying ◽

Cognitive Test Performance

ObjectiveDisease-modifying treatments (DMTs) are the gold standard for slowing disability progression in multiple sclerosis (MS), but their effects on cognitive impairment, a key symptom of the disease, are mostly unknown. We conducted a systematic review and meta-analysis to evaluate the differential effects of DMTs on cognitive test performance in relapsing-remitting MS (RRMS).MethodsPubMed, Scopus, and Cochrane Library were searched for studies reporting longitudinal cognitive performance data related to all major DMTs. The standardized mean difference (Hedges g) between baseline and follow-up cognitive assessment was used as the main effect size measure.ResultsForty-four studies, including 55 distinct MS patient samples, were found eligible for the systematic review. Twenty-five studies were related to platform therapies (mainly β-interferon [n = 17] and glatiramer acetate [n = 4]), whereas 22 studies were related to escalation therapies (mainly natalizumab [n = 14] and fingolimod [n = 6]). Reported data were mostly confined to the cognitive domain processing speed. A meta-analysis including 41 studies and 7,131 patients revealed a small to moderate positive effect on cognitive test performance of DMTs in general (g = 0.27, 95% confidence interval [CI] = [0.21–0.33]), but no statistically significant differences between platform (g = 0.27, 95% CI = [0.18–0.35]) and escalation therapies (g = 0.28, 95% CI = [0.19–0.37]) or between any single DMT and β-interferon.ConclusionsDMTs are effective in improving cognitive test performance in RRMS, but a treatment escalation mainly to amend cognition is not supported by the current evidence. Given the multitude of DMTs and their widespread use, the available data regarding differential treatment effects on cognitive impairment are remarkably scant. Clinical drug trials that use more extensive cognitive outcome measures are urgently needed.

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