Spinal fluid, oligoclonal bands and kappa free light chains
Why look at spinal fluid
The brain and spinal cord float in cerebrospinal fluid, which is made inside the brain and drains back into the blood. Because it bathes the nervous system, it carries traces of what the immune system is doing there. In MS the main question is whether antibodies are being made inside the nervous system itself, which is called intrathecal antibody synthesis. It happens in most people with MS and is evidence that the problem is inflammatory.
The lumbar puncture
Spinal fluid is taken by lumbar puncture. With the person lying on their side or sitting forward, a thin needle is passed between two vertebrae in the lower back, below the end of the spinal cord, and a few millilitres of fluid are collected. A blood sample is taken at the same time so the two can be compared. The commonest side effect is a headache that is worse when standing, which usually settles within days. Thinner, blunt-tipped needles make it less likely.
What is measured
A standard analysis covers more than antibodies.
- Cells. White cells are normal or only mildly raised in MS. A high count, or many neutrophils, points to another cause such as infection.
- Protein and albumin. Albumin is made only in the liver, so its ratio between fluid and blood shows how leaky the barrier is.
- IgG index. The ratio of antibody to albumin in fluid compared with blood. A raised index suggests antibody made inside the nervous system.
- Oligoclonal bands and kappa free light chains, described below.
- Tests for other diseases when the picture is unclear, such as infections.
Oligoclonal bands
The standard method separates the antibodies in paired samples of fluid and blood by their electrical charge on a gel (isoelectric focusing), then stains them for IgG. A healthy person's antibodies, made by millions of different cells, form a smooth smear. A small number of expanded antibody-making cell families each form a sharp band. Bands present in the fluid but not in the blood show antibody made inside the nervous system.
A systematic review of 71 studies found bands in 87.7 per cent of 12,253 people with MS and 68.6 per cent of 2,685 people with a first episode suggestive of MS. People with a first episode and positive bands had about ten times the odds of developing MS (odds ratio 9.88). The proportion with bands also varied with latitude. In a Barcelona cohort of 1,015 people with a first episode followed for a mean of almost seven years, bands raised the risk of MS and of reaching EDSS 3, independently of the MRI findings.
Bands are not specific to MS. They appear in infections of the nervous system and other inflammatory diseases, and about one person with MS in eight does not have them. They are found much less often in NMOSD and MOGAD, which helps tell those diseases apart (lesson 10.1).
Kappa free light chains
Antibodies are built from heavy and light chains, and antibody-making cells release spare light chains of two kinds, kappa and lambda. When antibodies are made inside the nervous system, kappa free light chains build up in the fluid. Their concentration, corrected for the barrier with the albumin ratio, gives the kappa index.
An international consensus found that intrathecal kappa light chains diagnose MS with sensitivity and specificity of about 90 per cent, similar to oligoclonal bands, with practical advantages: the test is automated, fast, cheaper, gives a number rather than a pattern read by eye, and does not depend on the person reading it. A 2025 consensus on the new criteria recommends a kappa index of 6.1 or more as the cut-off, and notes that bands and kappa light chains agree in about 90 per cent of cases, so occasionally both are worth measuring.
How the 2024 criteria use spinal fluid
The 2024 revision of the McDonald criteria allows kappa free light chains to be used in place of oligoclonal bands to show antibody production inside the nervous system. Positive spinal fluid can support a diagnosis in defined situations, and the criteria give extra guidance for people over 50 and people with other conditions that also cause white matter changes. The 2025 consensus adds that neurofilament light should not be used to make the diagnosis, although it may help with prognosis and monitoring.
Check yourself
What we know
- Antibody production inside the nervous system is found in most people with MS and strongly predicts MS after a first episode.
- Kappa free light chains match oligoclonal bands in accuracy and are now accepted in the diagnostic criteria.
- Neither test proves MS on its own, and a negative result does not exclude it.
What we don't know
- What the antibodies in MS spinal fluid recognise. Most of their targets are still unknown.
- Why the proportion with bands differs with latitude.
- Whether the kappa index can guide treatment decisions for an individual, beyond diagnosis.
In the research now
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Key terms
- Cerebrospinal fluid
- The clear fluid around the brain and spinal cord, sampled by lumbar puncture.
- IgG index
- A ratio comparing antibody levels in spinal fluid and blood, corrected for leakage. A raised index suggests antibody made in the nervous system.
- Isoelectric focusing
- A laboratory method that separates proteins by electrical charge on a gel, used to show oligoclonal bands.
- Kappa index
- The level of kappa free light chains in spinal fluid relative to blood, corrected for leakage.
- EDSS
- Expanded Disability Status Scale, from 0 (normal examination) to 10, the main disability measure in trials. Its middle range depends heavily on walking.
- Oligoclonal bands
- Distinct bands of antibodies found in spinal fluid but not matched in blood, showing antibody production inside the nervous system. They are common in MS but are not specific to it.
- Kappa free light chains
- Fragments of antibodies measured in spinal fluid. Raised levels show antibody production inside the nervous system and can support a diagnosis of MS.
- Lumbar puncture
- A procedure that takes a small sample of spinal fluid through a needle in the lower back.
- McDonald criteria
- The international criteria for diagnosing MS, last revised in 2024 and published in 2025.
- Neurofilament light (NfL)
- A protein released when nerve fibres are damaged. Blood levels can rise with new inflammation and fall on effective treatment. Other conditions can also affect its level.
References
- Freedman MS, et al. Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement. Arch Neurol 2005.https://doi.org/10.1001/archneur.62.6.865
- Dobson R, et al. Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude. J Neurol Neurosurg Psychiatry 2013.https://doi.org/10.1136/jnnp-2012-304695
- Tintore M, et al. Defining high, medium and low impact prognostic factors for developing multiple sclerosis. Brain 2015.https://doi.org/10.1093/brain/awv105
- Hegen H, et al. Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: a consensus statement. Mult Scler 2023.https://doi.org/10.1177/13524585221134217
- Deisenhammer F, et al. Positive cerebrospinal fluid in the 2024 McDonald criteria for multiple sclerosis. eBioMedicine 2025.https://doi.org/10.1016/j.ebiom.2025.105905
- Montalban X, et al. Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria. Lancet Neurol 2025.https://doi.org/10.1016/S1474-4422(25)00270-4
Next module · Imaging in depth
How MRI shows MS
MRI is the most important single test in MS. This lesson explains how the scanner makes its pictures, what each type of scan shows, and how to tell a new lesion from an old one.
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