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HelpTest Code LAB589 Multiple Sclerosis (MS) Cascade, Serum and Spinal Fluid
Additional Codes
|
Test Name in EPIC |
EPIC Test Code |
Mnemonic |
Mayo Test ID |
|---|---|---|---|
| MS Panel, CSF/Serum | LAB589 | MSP3 | MSP3 |
Specimen Required
Both serum and spinal fluid are required. Spinal fluid must be obtained within 1 week of serum collection.
Specimen Type: Spinal fluid
Container/Tube: Sterile vial
Specimen Volume: 1 mL
Collection Instructions:
1. Submit CSF from collection vial no. 4.(preferred); vial no. 1, 3, 2 are also acceptable (in this order).
2. Label specimen as spinal fluid.
Specimen Type: Serum
Supplies: Sarstedt Aliquot Tube 5 mL (T914)
Collection Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions:
1. Within 2 hours of collection, centrifuge and aliquot serum into a plastic vial.
2. Label specimen as serum.
Useful For
Diagnosing multiple sclerosis, especially helpful in patients with equivocal clinical or radiological findings
Profile Information
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| KCSFP | Kappa Free Light Chain, CSF | Yes, (KCSF) | Yes |
| XSRM | Additional sample for reflex OLIGS | No | Yes |
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| OLIGS | Serum Bands | Yes, (Order OLIG, submit CSF and Serum) | No |
| OLIGC | CSF Bands | Yes, (Order OLIG, submit CSF and Serum) | No |
Testing Algorithm
Kappa free light-chain testing will be performed by nephelometry on cerebral spinal fluid (CSF) samples. When kappa free light-chain testing indicates either borderline or positive results (≥0.0600 mg/dL), the oligoclonal banding test will be performed at an additional charge.
If the time of testing exceeds the specimen stability for oligoclonal banding tests, only kappa free light-chain testing will be performed. Kappa free light-chain testing will only be performed up to specimen stability.
For more information see Central Nervous System Demyelinating Disease Diagnostic Algorithm.
Method Name
KCSFP: Nephelometry
OLIGC, OLIGS: Isoelectric Focusing (IEF) with IgG Immunoblot Detection
Reporting Name
Multiple Sclerosis CascadeSpecimen Type
CSFSerum
Specimen Minimum Volume
Serum, Spinal fluid: 0.5 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| CSF | Frozen (preferred) | 14 days | |
| Refrigerated | 72 hours | ||
| Ambient | 24 hours | ||
| Serum | Frozen (preferred) | 14 days | |
| Ambient | 14 days | ||
| Refrigerated | 14 days |
Reject Due To
| Gross hemolysis | Reject |
| Gross lipemia | OK |
| Gross icterus | OK |
Clinical Information
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease characterized by visual, motor, and sensory disturbances. The diagnosis of MS is dependent on clinical, radiological, and laboratory findings. The detection of increased intrathecal immunoglobulin synthesis is the basis for current diagnostic laboratory tests for MS. These tests include the kappa free light chain detection in cerebrospinal fluid (CSF) and CSF oligoclonal bands detection.
Reference Values
KAPPA FREE LIGHT CHAIN
Medical decision point: 0.1000 mg/dL
Positive: ≥0.1000 mg/dL
Borderline: 0.0600 mg/dL-0.0999 mg/dL
Negative <0.0600 mg/dL
OLIGOCLONAL BANDS:
<2 bands
Interpretation
When result is less than 0.0600 mg/dL, the kappa free light-chain concentration measured in cerebrospinal fluid (CSF) is lower than the threshold associated with demyelinating disease. This is a negative result. Testing for oligoclonal banding is not performed. Clinical correlation is recommended.
When result is between 0.0600 and 0.0999 mg/dL, this is a borderline result. These findings are not specific for multiple sclerosis (MS) because CSF-specific immunoglobulin synthesis may also be detected in patients with other neurologic diseases (infectious, inflammatory, cerebrovascular, autoimmune, and paraneoplastic). Clinical correlation is recommended. Automatic reflexing to oligoclonal bands will occur.
When result is 0.1000 mg/dL or more, the kappa free light chain concentration measured in CSF is at or greater than the threshold associated with demyelinating disease. This is a positive result. These findings, however, are not specific for MS because CSF-specific immunoglobulin synthesis may also be detected in patients with other neurologic diseases (infectious, inflammatory, cerebrovascular, autoimmune, and paraneoplastic). Clinical correlation is recommended. Automatic reflexing to oligoclonal bands will occur.
A Mayo Clinic study published in 2018 with 325 patients suggested that a kappa free light-chain concentration in CSF greater than or equal to 0.06 mg/dL has 92% clinical sensitivity for the diagnosis of MS.(1)
A second, larger Mayo Clinic study with 1355 patients published in 2021 showed that a kappa CSF concentration greater than or equal to 0.06 mg/dL had approximately 89% sensitivity. When kappa value was greater than or equal to 0.1 mg/dL, it had similar sensitivity (87%) to the finding of two unique CSF oligoclonal bands (89%).(2)
Given the difference in thresholds based on these studies and highest sensitivity at the threshold of 0.06 mg/dL, any CSF kappa free light-chain result greater than or equal to 0.06 mg/dL will reflex to oligoclonal banding when the multiple sclerosis cascade test is ordered.
When the oligoclonal band assay detects 2 or more unique IgG bands in the CSF, the result is positive.
Cerebrospinal fluid is used in the diagnosis of MS by identifying increased intrathecal IgG synthesis qualitatively (oligoclonal bands). The presence of 2 or more unique CSF oligoclonal bands was reintroduced as one of the diagnostic criteria for MS in the 2017 revised McDonald criteria.(3) These findings, however, are not specific for MS as CSF-specific IgG synthesis may also be found in patients with other neurologic diseases including infectious, inflammatory, cerebrovascular, and paraneoplastic disorders. Clinical correlation is recommended.
Cautions
Increased intrathecal immunoglobulin synthesis may occur in other inflammatory central nervous system diseases, and therefore, these assays are not specific for multiple sclerosis.
Supportive Data
In a cohort of 1307 patients, where 159 had demyelinating disease, the Mayo Clinic oligoclonal banding test had a clinical sensitivity of 74% and clinical specificity of 89%, area under the ROC (receiver operating characteristic) curve of 0.813, when 2 or more unique cerebrospinal fluid (CSF) bands are used as a cutoff for positive. This kappa free light chain test, when considered positive at a concentration greater than or equal to 0.1000 mg/dL as a medical decision point, has a sensitivity of 70% with a specificity of 87%. The differences between the 2 tests are not statistically significant and the 2 tests show comparable performance with shorter turn-around-time for results and an objective quantitative result.
This panel combines the ease of use and interpretation of the quantitative measurement of kappa free light chains in CSF and allies it to the traditional interpretation of oligoclonal bands for optimized efficiency in laboratory testing for demyelinating diseases and improved test utilization.
Method Description
Kappa Free Light Chain:
Kappa free light chain is measured by nephelometric method in which the light scattered onto the antigen-antibody complexes is measured. The intensity of the measured scattered light is proportional to the amount of antigen-antibody complexes in the sample under certain conditions.(Instruction manual: Siemens Nephelometer II. Siemens, Inc; Version 2.3, 2008; Addendum to the Instruction Manual 2.4, 07/2019)
Oligoclonal Banding:
The oligoclonal banding assay requires paired cerebrospinal fluid (CSF) and serum samples. Unconcentrated CSF and diluted serum are electrophoresed by isoelectric focusing. The separated IgG bands are visualized by an IgG immunoblot, and oligoclonal bands present in the CSF and not in the serum are reported. The assay uses reagents from Helena Laboratories.(Saadeh RS, Ramos PA, Algeciras-Schimnich A, Flanagan EP, Pittock SJ, Willrich MA. An update on laboratory-based diagnostic biomarkers for multiple sclerosis and beyond. Clin Chem. 2022;68(9):1134-1150. doi:10.1093/clinchem/hvac061)
suggest removing for a more generic description of the method. Please look if there is a newer version of the package insert. Reagents are Binding Site, though.
Day(s) Performed
Monday through Friday
Report Available
3 to 5 daysSpecimen Retention Time
14 daysPerforming Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
This test has been modified from the manufacturer's instructions. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
83521
83916 x2 (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| MSP3 | Multiple Sclerosis Cascade | 100757-4 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| KCSFP | Kappa Free Light Chain, CSF | 48774-4 |
| XSRM | Additional sample for Reflex OLIGS | No LOINC Needed |
Forms
If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.