The good, the bands, and the ugly: do oligoclonal bands mean more brain shrinkage?

Oligoclonal bands (OCBs) are now back in the diagnostic criteria for MS - they can be used to support a diagnosis. If someone has a clinically-isolated syndrome - an episode of symptoms or signs due to demyelination without any evidence of previous events - the presence of OCBs makes it much more likely that they will go on to develop clinically-definite MS

Additionally, the presence of OCBs is associated with a higher chance of disability progression in defnite MS. Over 95% of people with clinically-definite MS have evidence of bands in their CSF. So, there's quite good evidence that these bands are telling us something meaningful about the disease process and are not just epiphenomena (a 'by-product').

OCBs are a strange phenomenon. When you take a sample of any fluid, you can separate out the proteins in it according to their size and charge. This is called electrophoresis. If you use this technique to look at the proteins in cerebrospinal fluid, you can detect a few distinct 'bands' of protein, which represent antibodies either being produced inside the CNS, or leaking into the CNS from the blood. These bands are detectable in the majority of pwMS (over 95% of people with definite MS), but can also occur in some infections of the CNS and other inflammatory diseases. In MS, these bands are typically present in CSF but not in blood, indicating that the antibodies are being produced inside the CNS.

This is what they look like:
nicked from the MS trust website

What is so strange and remarkable about these bands is that, although we know they are antibodies, we do not know...
1. Where they come from
2. What they recognise
3. Whether they are 'pathogenic' (involved in causing / perpetuating the disease)

Another marker of future disease progression that has generated lots of interest is brain atrophy (shrinkage). Atrophy is measured by MRI. It is clinically-important because it is thought to reflect neurodegeneration, which we know occurs from early in the disease and predicts long-term disability progression.

A new study looked at the relationship between OCBs and brain atrophy. PwMS were included if they had a new (<12 month) diagnosis of MS and had not had steroids in the preceding 30 days. 145 people were included, comprising:
- 20 pwMS without OCBs
- 25 pwMS with OCBs
- 15 healthy controls
The OCB-negative group were slightly older, slightly more male and had a slightly lower EDSS at baseline.

They compared brain volumes - as measured by MRI - between the three groups. The brain volumes included white matter volume (the connections between nerve cells), grey matter volume (the cell bodies of nerve cells), and total brain volume. 

Normalised white matter volume was significantly reduced in the group of pwMS who had OCBs, compared to both healthy controls and pwMS without OCBs. This effect was still significant after adjusting for differences in age, EDSS, and disease duration. There was no difference in whole brain volumes or grey matter volumes between the groups.

This is partly consistent with previous similar work. Other groups have reported an association between OCBs and increased grey matter atrophy and whole brain atrophy. It is therefore slightly surprising that these authors don't find the same thing, and only see an effect in the white matter.

This study is cross-sectional, and so we are seeing a snapshot in time. To show causation it would be useful to see that people with OCBs, when followed over time, develop more atrophy than people without OCBs.

The authors also don't control for previous or current disease-modifying therapy use. As we know that effective therapies can wipe out OCBs and slow brain atrophy, this is a major issue for me. One which limits interpretation of the findings considerably.

Another reason to be wary of overinterpreting these findings is that 'brain volume' on MRI is not the same thing as atrophy. Loss of brain volume can be a combination of loss of neurons, glia (supporting cells), and resolution of inflammation. The phenomenon in which the brain appears to shrink in the initial phase following DMT initiation is called 'pseudoatrophy', and is thought to reflect a reduction in inflammatory swelling rather than a genuine loss of brain tissue. As far as I can see the authors don't correct their volume measures for lesion count. 

So in short this is interesting stuff but I'm not wholly convinced, on the basis of this, that there is such a stark difference in brain atrophy between pwMS with and without OCBs. It will be important to follow these people over time to see whether the difference in white matter volume is robust and sustained. To really test the hypothesis that OCB+ MS and OCB- MS are different diseases, it would be great to see the results of the big phase III trials analysed according to OCB status. 




Oligoclonal bands of IgG (OB) are proposed as an early prognostic factor of the disease. Growing attention is directed towards brain volume evaluation as a possible marker of the severity of MS. Previous studies found that MS patients lacking OB have less brain atrophy.


to evaluate a possible relationship between OB and cerebral volume in a cohort of early MS patients.


Inclusion criteria were: diagnosis of relapsing-remitting MS; CSF analysis and MRI acquired simultaneously and within 12 months from clinical onset. A total of 15 healthy controls underwent MRI.


In 20 MS patients, CSF analysis did not show OB synthesis (OB negative group). A control group of 25 MS patients in whom OB was detected was also randomly recruited (OB positive group). T test showed a significant difference in NWV between the OB positive and OB negative groups (P value = 0.01), and between the OB positive group and the healthy controls (P value = 0.001). No differences were detected between OB negative group and healthy controls.
Multivariable linear regression showed a relationship between NWV and OB synthesis (P value = 0.02) controlling for age, gender, and EDSS.


Our preliminary results suggest that OB positive patients show more atrophy of white matter since early phases of the disease, supporting the role of CSF analysis as a prognostic factor in MS.