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

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.

scholarly journals The cerebrospinal fluid in multiple sclerosis: far beyond the bands

2017 ◽  
Vol 15 (1) ◽  
pp. 100-104 ◽  
Author(s):  
Renan Barros Domingues ◽  
Gustavo Bruniera Peres Fernandes ◽  
Fernando Brunale Vilela de Moura Leite ◽  
Charles Peter Tilbery ◽  
Rodrigo Barbosa Thomaz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Oligoclonal Bands ◽  
Fluid Analysis ◽  
Cerebrospinal Fluid Biomarkers ◽  
Therapeutic Decisions ◽  
Neuroimaging Data ◽  
Chemokine Ligand ◽  
New Biomarkers

ABSTRACT The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency. A more refined evaluation of disease and therapy status can contribute to better therapeutic choices, particularly in escalation of therapies. This is very relevant taking into account the availability of a greater number of drugs for multiple sclerosis treatment in recent years. In this review, we critically evaluate the current literature regarding the most important cerebrospinal fluid biomarkers in multiple sclerosis. The determination of biomarkers levels, such as chemokine ligand 13, fetuin A, and mainly light neurofilament has shown promising results in the evaluation of this disease, providing information that along with clinical and neuroimaging data may contribute to better therapeutic decisions.

Tear analysis in clinically isolated syndrome as new multiple sclerosis criterion

2009 ◽  
Vol 16 (1) ◽  
pp. 87-92 ◽  
Author(s):  
Gauthier Calais ◽  
Gerard Forzy ◽  
Charlotte Crinquette ◽  
Alexandre Mackowiak ◽  
Jerome de Seze ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Magnetic Resonance ◽  
Isoelectric Focusing ◽  
Clinically Isolated Syndrome ◽  
Oligoclonal Bands ◽  
Resonance Imaging ◽  
Magnetic Resonance Imaging Mri ◽  
Tear Analysis

In clinically isolated syndrome (CIS), the detection of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) is critical for space dissemination validation when magnetic resonance imaging (MRI) diagnostic criteria are not fulfilled. However, lumbar puncture for CSF collection is considered relatively invasive. Previous studies have demonstrated applicability of OCB detection in tears to the diagnosis of multiple sclerosis (MS). The objective of the present study was to assess concordance between OCB detection in tears and in CSF. We have prospectively included patients with CIS and compared results of CSF and tear OCB detection by isoelectric focusing (IEF). Tears were collected using a Schirmer strip. We included 82 patients. For 69 of them, samples were analysable. OCBs were detected in CSF for 63.8% and in tears for 42% of patients. All patients with tear OCBs had CSF OCBs. We suggest that tear OCB detection may replace CSF OCB detection as a diagnostic tool in patients with CIS. This would circumvent the practice of invasive lumbar punctures currently used in MS diagnosis.

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

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.

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

2012 ◽  
Vol 70 (8) ◽  
pp. 574-577 ◽  
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.

scholarly journals Pediatric Multiple Sclerosis in Portugal: A Multicentre Study

2016 ◽  
Vol 29 (7-8) ◽  
pp. 425 ◽  
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.

Early predictors of multiple sclerosis after a typical clinically isolated syndrome

2014 ◽  
Vol 20 (13) ◽  
pp. 1721-1726 ◽  
Author(s):  
Aurélie Ruet ◽  
Georgina Arrambide ◽  
Bruno Brochet ◽  
Cristina Auger ◽  
Eva Simon ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
At Risk ◽  
High Specificity ◽  
Clinically Isolated Syndrome ◽  
Oligoclonal Bands ◽  
Mcdonald Criteria ◽  
Early Predictors ◽  
Patients At Risk ◽  
Magnetic Resonance Imaging Mri ◽  
Periventricular Lesions

Background: The 2010 McDonald criteria allow diagnosing multiple sclerosis (MS) with one magnetic resonance imaging (MRI) scan. Nevertheless, not all patients at risk fulfil criteria at baseline. Other predictive factors (PFs) are: age ≤40 years, positive oligoclonal bands (OBs), and ≥3 periventricular lesions. Objective: The purpose of this study was to evaluate the 2010 McDonald criteria performance and to assess other PFs in patients without dissemination in space (DIS). Methods: Patients with clinically isolated syndrome (CIS) underwent baseline MRI and OB determination with clinical and radiological follow-up. Adjusted hazard ratios (aHRs) for clinically definite MS were estimated for DIS, dissemination in time (DIT), and DIS+DIT. Diagnostic properties at two years were calculated. In cases without DIS, combinations of ≥2 PFs were assessed. Results: A total of 652 patients were recruited; aHRs were 3.8 (2.5–5.8) for DIS, 4.2 (1.9–9.2) for DIT, and 8.6 (5.4–13.8) for DIS+DIT. Sensitivities were 69.6%, 42.3%, and 36.4%, and specificities were 67.3%, 87.9%, and 90.2%, respectively. In patients without DIS, aHRs varied between 2.7–5.5 and specificities ranged from 73.5–89.7% for PF combinations. Conclusion: The high specificity of the 2010 McDonald criteria is confirmed. In patients without DIS, PF combinations could be helpful in identifying those at risk for MS.

Cerebrospinal fluid oligoclonal bands and progression of disability in multiple sclerosis

2007 ◽  
Vol 14 (7) ◽  
pp. 797-800 ◽  
Author(s):  
M. Koch ◽  
D. Heersema ◽  
J. Mostert ◽  
A. Teelken ◽  
J. De Keyser
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Oligoclonal Bands

The contribute of cerebrospinal fluid free light-chain assay in the diagnosis of multiple sclerosis and other neurological diseases in an Italian multicenter study

2021 ◽  
pp. 135245852110641
Author(s):  
Gaetano Bernardi ◽  
Tiziana Biagioli ◽  
Paola Malpassi ◽  
Teresa De Michele ◽  
Domizia Vecchio ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Disorders ◽  
Operating Characteristic ◽  
Neurological Diseases ◽  
Characteristic Curve ◽  
Oligoclonal Bands ◽  
Free Light Chains ◽  
Complementary Information ◽  
Combined Use

Background: Cerebrospinal fluid (CSF) free light chains (FLCs) can be an alternative assay to oligoclonal bands (OCBs) in inflammatory neurological disorders, but threshold has no consensus. Objective: To assess the diagnostic accuracy of CSF FLCs in multiple sclerosis (MS) and other neurological diseases. Methods: A total of 406 patients from five Italian centers. FLCs were measured in CSF and serum using Freelite MX assays on Optilite. Results: A total of 171 patients were diagnosed as MS, 154 non-inflammatory neurological diseases, 48 inflammatory central nervous system (CNS) diseases, and 33 peripheral neurological diseases. Both kFLC and λFLC indices were significantly higher in patients with MS compared to other groups ( p < 0.0001). The kFLC index ⩾ 6.4 is comparable to OCB for MS diagnosis (area under the receiver operating characteristic curve (AUC) = 0.876; sensitivity 83.6% vs 84.2%; specificity 88.5% vs 90.6%). λFLC index ⩾ 5 showed an AUC of 0.616, sensitivity of 33.3% and specificity of 90.6%. In all, 12/27 (44.4%) MS patients with negative OCB had kFLC index ⩾ 6.4. Interestingly, 37.5% of 24 patients with a single CSF IgG band showed high kFLC index and 12.5% positive λFLC index. Conclusion: Our findings support the diagnostic utility of FLC indices in MS and other CNS inflammatory disorders, suggesting a combined use of FLC and OCB to help clinicians with complementary information.

Two agarose electrophoretic systems for demonstration of oligoclonal bands in cerebrospinal fluid compared.

1980 ◽  
Vol 26 (2) ◽  
pp. 343-345 ◽  
Author(s):  
B Gerson ◽  
F J Krolikowski ◽  
I M Gerson
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
High Resolution ◽  
Thin Layer ◽  
Oligoclonal Bands ◽  
System Sensitivity ◽  
Electrophoretic Patterns ◽  
Clinical Laboratories ◽  
Two Systems

Abstract Demonstration of oligoclonal bands by electrophoresis of cerebrospinal fluid is an important aid in establishing the diagnosis of multiple sclerosis. Electrophoretic systems vary in their effectiveness in doing so. We compared two systems in this respect. For a thin-layer agarose system, sensitivity was less (47%) than for a high-resolution agarose system (87%). Each system had good specificity (92 and 85%, respectively). Interpretation of electrophoretic patterns for cerebrospinal fluid should be available in clinical laboratories. Further, the best available system should be used for demonstration of oligoclonal bands.

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