Oligoclonal Bands in Cerebrospinal Fluid of Black Patients with Multiple Sclerosis

Genetic susceptibility is a well-recognized factor in the onset of multiple sclerosis (MS). The objective of this study was to determine the frequency of oligoclonal bands (OCB) restricted to the cerebrospinal fluid, in an ethnically mixed group of MS patients in the city of São Paulo, Brazil. Techniques used to detect OCB consisted of isoelectric focusing followed by immunoblotting. OCB were found in 49 (54.4%) out of 90 patients with clinically definite MS; out of the 23 brown/black patients, 17 (73.9%) were OCB+; out of the 66 white patients, 32 (48.5%) were OCB+; and the only patient yellow was OCB+ (p=0.05). Analysis of the IgG index was also consistent with the findings, but with lower statistical significance. The data presented in our study show that the ethnic differences in MS extend to the immune response.

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Cerebrospinal fluid free kappa light chains and kappa index perform equal to oligoclonal bands in the diagnosis of multiple sclerosis

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2018-0400 ◽

2018 ◽

Vol 57 (2) ◽

pp. 210-220 ◽

Cited By ~ 9

Author(s):

Mikael Christiansen ◽

Mikkel Carstensen Gjelstrup ◽

Morten Stilund ◽

Tove Christensen ◽

Thor Petersen ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Sensitivity And Specificity ◽

Diagnostic Performance ◽

Oligoclonal Bands ◽

Light Chains ◽

Kappa Index ◽

Absolute Concentration ◽

Igg Index ◽

The Absolute

AbstractBackgroundDetection of intrathecal immunoglobulin G (IgG) synthesis by gold standard oligoclonal bands (OCB) or IgG index remains an integral part of multiple sclerosis (MS) diagnostics, although both methods have weaknesses. Emerging evidence suggests that automated detection of free light chains (FLC) in the cerebrospinal fluid (CSF) has diagnostic performance equal to OCB. The objective of this study was to compare the diagnostic performance of CSF FLC with OCB and IgG index in a large cohort of Scandinavian patients referred for MS evaluation.MethodsWe prospectively included 230 patients suspected for MS. They are composed of patients with MS (n=96), clinically isolated syndrome (n=37), other neurological diseases (OND, n=31) and symptomatic controls (SC, n=66). CSF and serum samples were analyzed for kappa and lambda FLC, OCB and IgG index. Diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis.ResultsBoth the absolute concentration of CSF-kappa and the kappa index had excellent MS diagnostic performances with ROC area under the curve of 0.93 and 0.94 (MS vs. SC+OND). At the 0.42 mg/L cutoff, CSF-kappa had sensitivity and specificity of 93.8% and 85.6%, whereas sensitivity and specificity for OCB was 82.3% and 93.8% (72.9% and 95.9% for IgG index at cutoff 0.64). CSF-lambda and lambda index performed inferior to CSF-kappa and kappa index.ConclusionsCSF-kappa and kappa index represent automated, rapid and low-cost alternatives to OCB. Using merely the absolute concentration of CSF-kappa is a logistic advantage in the clinical laboratories.

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Effects of natalizumab on oligoclonal bands in the cerebrospinal fluid of multiple sclerosis patients: A longitudinal study

Multiple Sclerosis Journal ◽

10.1177/1352458514538111 ◽

2014 ◽

Vol 20 (14) ◽

pp. 1900-1903 ◽

Cited By ~ 27

Author(s):

R Mancuso ◽

D Franciotta ◽

M Rovaris ◽

D Caputo ◽

A Sala ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Longitudinal Study ◽

Retrospective Studies ◽

Oligoclonal Bands ◽

Igg Index ◽

Before And After ◽

Oligoclonal Igg ◽

Multiple Sclerosis Patients

Retrospective studies show that natalizumab modifies oligoclonal immunoglobulin (IgG) bands (OCBs) in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. In this study, we prospectively analyzed both serum and CSF samples from 24 MS patients, before and after 2 years of natalizumab-based therapy. Our results showed complete (55%) or partial (27%) disappearance of the OCBs in CSF samples that were taken after 2 years of therapy. Intrathecal IgG production, represented by the IgG index and IgGLoc, was also quantitatively reduced. Our data showed that natalizumab substantially modulates both intrathecal polyclonal and oligoclonal IgG production: This effect was much more potent than was previously reported.

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CORRELATION OF THE IGG INDEX AND OLIGOCLONAL BANDS IN THE CEREBROSPINAL FLUID OF PATIENTS WITH MULTIPLE SCLEROSIS

Biomedical Papers ◽

10.5507/bp.2008.038 ◽

2008 ◽

Vol 152 (2) ◽

pp. 247-249 ◽

Cited By ~ 11

Author(s):

Jan Mares ◽

Roman Herzig ◽

Karel Urbanek ◽

Vladimira Sladkova ◽

Jaroslava Sklenarova ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Oligoclonal Bands ◽

Igg Index

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Study of oligoclonal bands restricted to the cerebrospinal fluid in multiple sclerosis patients in the city of São Paulo

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2009000600011 ◽

2009 ◽

Vol 67 (4) ◽

pp. 1017-1022 ◽

Cited By ~ 12

Author(s):

Paulo Diniz da Gama ◽

Luís dos Ramos Machado ◽

José Antonio Livramento ◽

Hélio Rodrigues Gomes ◽

Tarso Adoni ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Sao Paulo ◽

Oligoclonal Bands ◽

Control Group ◽

São Paulo ◽

The Central Nervous System ◽

Different Populations ◽

Multiple Sclerosis Patients ◽

The City

The frequency of oligoclonal bands (OCB) restricted to the cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) varies widely in different populations. The objective of this study was to determine the frequency of these OCB in a group of MS patients in the city of São Paulo. Techniques used to detect OCB consisted of isoelectric focusing followed by immunoblotting. Oligoclonal bands were found in 49 (54.4%) out of 90 patients with clinically definite MS; in (31.2%) of the 16 patients with clinically isolated syndrome; in 7 (17.9%) of 39 patients with inflammatory disorders of the central nervous system (IDCNS), and in none of the individuals with no neurological condition (control group). The specificity of the method was 100% when compared to the control group and 82.1% when compared to the IDCNS group. These results suggest that the frequency of CSF OCB is much lower in Brazilian MS patients from São Paulo city than that reported in MS series from Caucasian populations.

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Oligoclonal Bands and the IgG Index in Multiple Sclerosis: Uses and Limitations

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456328902600403 ◽

1989 ◽

Vol 26 (4) ◽

pp. 317-323 ◽

Cited By ~ 6

Author(s):

P D Giles ◽

J P Heath ◽

S J Wroe

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Clinical Significance ◽

Screening Test ◽

Diagnostic Value ◽

Diagnostic Sensitivity ◽

Oligoclonal Bands ◽

Igg Index ◽

The Relationship ◽

Immunoblotting Technique

The relationship between two tests commonly used in the investigation of multiple sclerosis (MS), the IgG index and oligoclonal bands, has been assessed. Using an immunoblotting technique specific for IgG, analysis of cerebrospinal fluid for oligoclonal bands was found to provide greater diagnostic sensitivity than the IgG index without any loss of specificity. In patients without oligoclonal bands the IgG index had no diagnostic value for MS and in the presence of bands the magnitude of the index was unrelated to the clinical certainty of the diagnosis. High values of the IgGindex were invariably associated with the presence of oligoclonal bands and the IgG index appeared to have no clinical significance independent of this relationship. Even as a screening test the IgG index has serious limitations.

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Natalizumab Induces Changes of Cerebrospinal Fluid Measures in Multiple Sclerosis

Diagnostics ◽

10.3390/diagnostics11122230 ◽

2021 ◽

Vol 11 (12) ◽

pp. 2230

Author(s):

Ranjani Ganapathy Subramanian ◽

Dana Horakova ◽

Manuela Vaneckova ◽

Balazs Lorincz ◽

Jan Krasensky ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Mixed Models ◽

Brain Volume ◽

Oligoclonal Bands ◽

Volume Loss ◽

Brain Volume Loss ◽

Igg Index ◽

Natalizumab Treatment

Background: There is a lack of knowledge about the evolution of cerebrospinal fluid (CSF) markers in multiple sclerosis (MS) patients undergoing natalizumab treatment. Aim: We aimed to evaluate the effect of natalizumab on basic inflammatory CSF and MRI measures. Methods: Together, 411 patients were screened for eligibility and 93 subjects with ≥2 CSF examinations ≤6 months before and ≥12 months after natalizumab initiation were recruited. The effect of natalizumab on CSF as well as clinical and paraclinical measures was analyzed using adjusted mixed models. Results: Natalizumab induced a decrease in CSF leukocytes (p < 1 × 10−15), CSF protein (p = 0.00007), the albumin quotient (p = 0.007), the IgG quotient (p = 6 × 10−15), the IgM quotient (p = 0.0002), the IgG index (p = 0.0004), the IgM index (p = 0.003) and the number of CSF-restricted oligoclonal bands (OCBs) (p = 0.0005). CSF-restricted OCBs positivity dropped from 94.6% to 86% but 26 patients (28%) had an increased number of OCBs at the follow-up. The baseline to follow-up EDSS and T2-LV were stable; a decrease in the relapse rate was consistent with a decrease in the CSF inflammatory markers and previous knowledge about the effectiveness of natalizumab. The average annualized brain volume loss during the follow-up was −0.50% (IQR = −0.96, −0.16) and was predicted by the baseline IgM index (B = −0.37; p = 0.003). Conclusions: Natalizumab is associated with a reduction of basic CSF inflammatory measures supporting its strong anti-inflammatory properties. The IgM index at the baseline predicted future brain volume loss during the course of natalizumab treatment.

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Torticollis as an Initial Manifestation of a Seronegative Demyelinating Disorder in a Child: A Case Report

Journal of Pediatric Neurology ◽

10.1055/s-0041-1736599 ◽

2021 ◽

Author(s):

Sandesh Kini ◽

Yellanthoor Ramesh Bhat ◽

Lakshmikanth Halegubbi Karegowda

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Case Report ◽

Demyelinating Disease ◽

Oligoclonal Bands ◽

Initial Manifestation ◽

Demyelinating Disorder ◽

The Brain

AbstractTorticollis refers to a condition in which the head is persistently tilted to one side, sometimes associated with pain. Torticollis in a child can be congenital or acquired. Torticollis as an initial manifestation of an underlying demyelinating syndrome is quite rare in children. Here, we report a 7-year-old girl who presented with persistent torticollis. Neuroimaging of the brain revealed features of a demyelinating disease. Further studies did not show any evidence of multiple sclerosis. Cerebrospinal fluid was negative for antiaquaporin-4 antibodies, antimyelin oligodendrocyte glycoprotein antibodies, and oligoclonal bands. A seronegative demyelinating disorder was considered. She was treated with pulsed methylprednisolone therapy. She responded well to steroids with no progression of illness during follow-up. Torticollis was partially improved.

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Oligoclonal bands in the cerebrospinal fluid and increased brain atrophy in early stages of relapsing-remitting multiple sclerosis

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2012000800003 ◽

2012 ◽

Vol 70 (8) ◽

pp. 574-577 ◽

Cited By ~ 4

Author(s):

Juan Ignacio Rojas ◽

Liliana Patrucco ◽

Santiago Tizio ◽

Edgardo Cristiano

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Brain Atrophy ◽

Disease Onset ◽

Oligoclonal Bands ◽

Matter Volume ◽

Early Stages ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Relapsing Remitting Multiple Sclerosis

OBJECTIVE: To determine if the presence of oligoclonal bands (OB) at early stages of multiple sclerosis was associated with higher brain atrophy, when compared with patients without OB. METHODS: Relapsing-remitting multiple sclerosis (RRMS) patients with less than two years of disease onset and OB detection in cerebrospinal fluid (CSF) were included. SIENAX was used for total brain volume (TBV), gray matter volume (GMV), and white matter volume (WMV). RESULTS: Forty patients were included, 29 had positive IgG-OB. No differences were found between positive and negative patients in gender, expanded disability status scale (EDSS), treatment received, and T2/T1 lesion load. TBV in positive IgG-OB patients was 1.5 mm³ x 10(6) compared with 1.64 mm³ x 10(6) in the negative ones (p=0.02). GMV was 0.51 mm³ x 10(6) in positive IgG-OB compared with 0.62 mm³ x 10(6) in negative ones (p=0.002). No differences in WMV (p=0.09) were seen. CONCLUSIONS: IgG-OB in the CSF was related to neurodegeneration magnetic resonance (MR) markers in early RRMS.

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Pediatric Multiple Sclerosis in Portugal: A Multicentre Study

Acta Médica Portuguesa ◽

10.20344/amp.6346 ◽

2016 ◽

Vol 29 (7-8) ◽

pp. 425 ◽

Cited By ~ 1

Author(s):

Ana Sofia Correia ◽

Luís Augusto ◽

Joana Meireles ◽

Joana Pinto ◽

Ana Paula Sousa

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Brain Magnetic Resonance Imaging ◽

Oligoclonal Bands ◽

Childhood Onset ◽

Multicentric Study ◽

Pediatric Multiple Sclerosis ◽

Adolescent Groups ◽

Reported Data ◽

Cerebrospinal Fluid Pleocytosis

Introduction: Multiple sclerosis is most often diagnosed among young adults but less frequently it may present during childhood or adolescence. In Portugal, there has been only one previous single-center, pediatric multiple sclerosis study. The main objective was the evaluation of the demographic, clinical, laboratorial and neuroradiological characteristics of patients with pediatric-onset multiple sclerosis in Portugal. The secondary objectives were to compare the characteristics of childhood-onset multiple sclerosis and adolescent-onset multiple sclerosis and to characterize the treatments prescribed.Material and Methods: We performed a retrospective observational, multicentric study. We reviewed data of all patients with multiple sclerosis younger than 18 years at the onset of their first multiple sclerosis symptoms.Results: There were 46 patients (72% female) included with a mean age at diagnosis of 16.1 years. Six cases had childhood-onset and 40 cases had adolescence-onset. The median value of Expanded Disability Status Scale was two. Relapsing-remitting multiple sclerosis was most prevalent (98% of cases). In the cerebrospinal fluid study, 74% of patients had positive oligoclonal bands. Brain magnetic resonance imaging studies showed a predominant supratentorial involvement (98% of cases), whereas the cervical segment was the most frequently affected in the spinal cord. All the patients enrolled in the study underwent immunomodulatory therapy, 75% ofpatients with beta-interferon. Concerning differences between the childhood and the adolescent groups, we found a greater proportion of male patients and of individuals with cerebrospinal fluid pleocytosis among the childhood-onset group.Discussion: This study provides new data on pediatric multiple sclerosis characteristics in Portugal and our results are similar to previously reported data in other parts of the worldConclusion: This is the first multicentric study characterizing pediatric multiple sclerosis in Portugal. The mechanisms underlying the particularities of pediatric multiple sclerosis remain largely unknown and further studies are required.

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Integrative biochemical, proteomics, and metabolomics cerebrospinal fluid biomarkers predict clinical conversion to multiple sclerosis

Brain Communications ◽

10.1093/braincomms/fcab084 ◽

2021 ◽

Author(s):

Fay Probert ◽

Tianrong Yeo ◽

Yifan Zhou ◽

Megan Sealey ◽

Siddharth Arora ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Predictive Accuracy ◽

Personalised Medicine ◽

Clinically Isolated Syndrome ◽

Oligoclonal Bands ◽

Protein Biomarkers ◽

Glucose Levels ◽

Prognostic Accuracy ◽

New Biomarkers

Abstract Eighty-five percent of multiple sclerosis cases begin with a discrete attack termed clinically isolated syndrome, but 37% of clinically isolated syndrome patients do not experience a relapse within 20 years of onset. Thus, the identification of biomarkers able to differentiate between individuals who are most likely to have a second clinical attack from those who remain in the clinically isolated syndrome stage is essential to apply a personalised medicine approach. We sought to identify biomarkers from biochemical, metabolic, and proteomic screens that predict clinically defined conversion from clinically isolated syndrome to multiple sclerosis and generate a multi-omics-based algorithm with higher prognostic accuracy than any currently available test. An integrative multi-variate approach was applied to the analysis of cerebrospinal fluid samples taken from 54 individuals at the point of clinically isolated syndrome with 2–10 years of subsequent follow-up enabling stratification into clinical converters and non-converters. Leukocyte counts were significantly elevated at onset in the clinical converters and predict occurrence of a second attack with 70% accuracy. Myo-inositol levels were significantly increased in clinical converters while glucose levels were decreased, predicting transition to multiple sclerosis with accuracies of 72% and 63%, respectively. Proteomics analysis identified 89 novel gene products related to conversion. The identified biochemical and protein biomarkers were combined to produce an algorithm with predictive accuracy of 83% for the transition to clinically defined multiple sclerosis, outperforming any individual biomarker in isolation including oligoclonal bands. The identified protein biomarkers are consistent with an exaggerated immune response, perturbed energy metabolism, and multiple sclerosis pathology in the clinical converter group. The new biomarkers presented provide novel insight into the molecular pathways promoting disease while the multi-omics algorithm provides a means to more accurately predict whether an individual is likely to convert to clinically defined multiple sclerosis.

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