Kappa Index Versus Csf Oligoclonal Bands in Diagnosis of ms and Prediction of Disease Activity

Kappa Index Versus Csf Oligoclonal Bands in Diagnosis of Multiple Sclerosis and Prediction of Disease

To:

1. Compare the diagnostic performance of cerebrospinal fluid kappa index to that of cerebrospinal fluid IgG oligoclonal bands in differentiating multiple sclerosis from other inflammatory and non-inflammatory neurological diseases .
2. Assess the role of kappa free light chain and oligoclonal bands in predicting disease activity (conversion from clinical isolated syndrome to multiple sclerosis)

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Diagnostic test: kappa index

Detailed Description

Multiple sclerosis is a chronic inflammatory immune-mediated disorder of the central nervous system.Diagnosis requires the combination of clinical signs and symptoms with paraclinical findings obtained by magnetic resonance imaging and cerebrospinal fluid analysis .which are componants of the 2017 McDonald criteria .So far, the gold standard for demonstrating intrathecal IgG synthesis is represented by selective oligoclonal bands in cerebrospinal fluid by isoelectric focusing (IEF), alongside an elevated IgG index .However, the detection of oligoclonal bands in cerebrospinal fluid has several limits as , it requires a time-consuming and expensive laboratory technique, with about three hours needed to obtain results Furthermore, it only provides aqualitative information about the presence of IgG in CSF .During CNS inflammation , kappa free light chain are secreted in the CSF and their concentration reflect the degree of intrathecal B cells and plasma cells activation .Measurement of KFLC could help diagnosis of OCB negative MS and identify intrathecal immunoglobulin synthesis in patient presenting with one isolated band on isoelectric focusing , and it is fully automated,rater independent, stable against preanalytical errors . Thus, the intrathecal synthesis of free light chains are more sensitive, less costly, and less time-consuming compared To OCB detection .The most reliable parameter used to assess FLC diagnostic value in MS is the k-index, .So κ-FLC index predicted the time to conversion to MS as well as disability progression . So patients with early MS and high κ-FLC index is an independent risk factor for conversion from CIS to MS

• Study Type: Observational
• Enrollment (Estimated): 140

Contacts and Locations

• Study Contact: Name: reham abdelsater, assistant lecturer; Phone Number: 01024478076; Email: rehamabdelsater@gmail.com
• Study Contact Backup: Name: Madeha Younis bakheet, professor; Phone Number: 01009344150; Email: m.younis@aun.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

we will select for this study 140 patients including control group and patients group aged between 18 -40

Description

Inclusion Criteria:

• Patients diagnosed with CIS or MS according to the 2017 revision of the McDonald criteria
• Patients diagnosed with RIS (Radiological isolated syndrome) according to the criteria by Okuda
• Age between 18 and 40 years.

Exclusion Criteria:

• History of exposure, in the 30 days prior to CSF collection, to immunosuppressant or immunomodulatory therapies .
• Peripheral neurological disorders .
• Infectious CNS disease.
• CNS tumor.
• Monoclonal gammopathy .
• Chronic kidney injury (GFR <30 ml /min/1.75m2 )

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; (-ve OCB )(70 patients) Control group which include patients with inflammatory and non-inflammatory neurological diseases (such as cerebral small vessel disease or unspecific white matter lesion )	Diagnostic test: kappa index; CSF albumin /serum albumin ratio (Qalb) k-index = (CSF kFLC/serum kFLC)/Qalb
2; (+ve OCBs )(70 patients) Patients presenting for the diagnostic workup, including CSF analysis , of clinical and/or MRI suspicion of MS or CIS.	Diagnostic test: kappa index; CSF albumin /serum albumin ratio (Qalb) k-index = (CSF kFLC/serum kFLC)/Qalb

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the diagnostic performance of CSF k index in differentiating MS from other inflammatory and non-inflammatory neurological diseases .	measure specificity and sensitivity of kappa free light chain	baseline
Assess the diagnostic performance of CSF IgG OCBs in differentiating MS from other inflammatory and non-inflammatory neurological diseases .	measure specificity and sensitivity of cerebrospinal fluid oligoclonal bands	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the role of k FLC in predicting disease activity (conversion from CIS to MS)	measure positive predictive value and negative predictive value of kappa free light chain	baseline
Assess the role of OCBs in predicting disease activity (conversion from CIS to MS)	measure positive predictive value and negative predictive value of oligoclonal bands	baseline

Collaborators and Investigators

• Sponsor: Assiut University

Publications and helpful links

General Publications

• Gaetani L, Di Carlo M, Brachelente G, Valletta F, Eusebi P, Mancini A, Gentili L, Borrelli A, Calabresi P, Sarchielli P, Ferri C, Villa A, Di Filippo M. Cerebrospinal fluid free light chains compared to oligoclonal bands as biomarkers in multiple sclerosis. J Neuroimmunol. 2020 Feb 15;339:577108. doi: 10.1016/j.jneuroim.2019.577108. Epub 2019 Nov 7.
• Duell F, Evertsson B, Al Nimer F, Sandin A, Olsson D, Olsson T, Khademi M, Hietala MA, Piehl F, Hansson M. Diagnostic accuracy of intrathecal kappa free light chains compared with OCBs in MS. Neurol Neuroimmunol Neuroinflamm. 2020 Jun 11;7(4):e775. doi: 10.1212/NXI.0000000000000775. Print 2020 Jul.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: March 30, 2024
• First Submitted That Met QC Criteria: April 16, 2024
• First Posted (Actual): April 18, 2024

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: kappa index in ms

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No