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HelpTest ID: MSP3 Multiple Sclerosis (MS) Cascade, Serum and Spinal Fluid
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 |
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.
Clinical Reference
1. Gurtner KM, Shosha E, Bryant SC, et al. CSF free light chain identification of demyelinating disease: comparison with oligoclonal banding and other CSF indexes. Clin Chem Lab Med. 2018;56(7):1071-1080
2. Saadeh RS, Bryant SC, McKeon A, et al. CSF kappa free light chains: cutoff validation for diagnosing multiple sclerosis. Mayo Clin Proc. 2022;97(4):738-751. doi:10.1016/j.mayocp.2021.09.014
3. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162-173
4. McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis: A review. JAMA. 2021;325(8):765-779. doi:10.1001/jama.2020.26858
5. Hegen H, Walde J, Milosavljevic D, et al. Free light chains in the cerebrospinal fluid. Comparison of different methods to determine intrathecal synthesis. Clin Chem Lab Med. 2019;57(10):1574-1586. doi:10.1515/cclm-2018-1300
6. Hegen H, Zinganell A, Auer M, Deisenhammer F. The clinical significance of single or double bands in cerebrospinal fluid isoelectric focusing. A retrospective study and systematic review. PLoS One. 2019;14(4):e0215410. doi:10.1371/journal.pone.0215410
7. Deisenhammer F, Zetterberg H, Fitzner B, Zettl UK. The Cerebrospinal fluid in multiple sclerosis. Front Immunol. 2019;10:726. doi:10.3389/fimmu.2019.00726
8. Susse M, Hannich M, Petersmann A, et al. Kappa free light chains in cerebrospinal fluid to identify patients with oligoclonal bands. Eur J Neurol. 2018;25(9):1134-1139. doi:10.1111/ene.13667
9. Hegen H, Arrambide G, Gnanapavan S, et al. Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A consensus statement. Mult Scler. 2023;29(2):182-195. doi:10.1177/13524585221134217
10. Hegen H, Walde J, Berek K, et al. Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A systematic review and meta-analysis. Mult Scler. 2023;29(2):169-181. doi:10.1177/13524585221134213
Day(s) Performed
Monday through Friday
Report Available
3 to 5 daysTest 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.
Special Instructions
mml-Demyelinating-Diseases