Analysing tears to diagnose multiple sclerosis
An accurate diagnosis of multiple sclerosis is a challenge since over one hundred conditions resemble MS. Until recently, one of the most common tests used to help in the diagnosis was a lumbar puncture (spinal tap), in which a needle is inserted into the spinal cord to extract cerebrospinal fluid (CSF). Lumbar puncture is difficult to perform, painful to the person on the receiving end, and unpleasant for everyone concerned.
So doctors were happy to let technology trump tradition and use magnetic resonance imaging (MRI) as the preferred procedure to confirm the diagnosis. This shift was reflected in the most recent update of the criteria used to diagnose MS (called the McDonald criteria; Polman and colleagues. Ann Neurol 2011;69:292-302). [The article is available as a free download in the MSology Library: http://msology.ca/msology-library-diagnosis.]
The purpose of lumbar puncture was to detect oligoclonal bands (OCBs), which are made up of antibodies (immunoglobulins) produced by a type of immune cell (called B cells). This immune activity isn’t normally seen in the central nervous system, so it indicates that something is wrong, such as infection or abnormal immune activation. About 88% of people with MS are positive for OCBs in their spinal cord (Dobson and colleagues. J Neurol Neurosurg Psychiatry 2013;84:909-914).
The frequent finding of OCBs in MS led to two important questions. The immune dysfunction in MS was thought to involve primarily T cells, which mistake the myelin that insulates nerve fibres as “foreign” and attack it, resulting in demyelination and nerve damage. But OCBs indicate B cell activity (a different type of immune cell). So the first question was: why is there B cell activity in the central nervous system? This in turn has led to studies of medications that target B cells (such as rituximab, ocrelizumab and ofatumumab) as possible therapies for MS. One of these drugs – ocrelizumab – may become available in some countries in 2015 as an MS treatment.
The second question was whether OCBs had any value in predicting the severity of a person’s MS. About two-thirds of people with “pre-MS” (called clinically isolated syndrome [CIS]) have OCBs, and they have a much higher risk of developing MS if OCBs are present. In a similar vein, people with OCBs at the time of their MS diagnosis have a higher risk of developing disability later on (Dobson 2013).
This suggested that lumbar puncture wasn’t only a useful tool for diagnosing MS. It could also be useful for predicting the severity of MS. This is important to know upfront because it gives a person some sense of how aggressively their MS needs to be treated.
All of which doesn’t make lumbar punctures any more pleasant. However, several studies have now looked at a different method of detecting OCBs – by turning to the tear ducts.
A decade ago, a study found that analysing a person’s tears was just as good as CSF for detecting OCBs (Devos and colleagues. J Neurol 2001;248):672-675). This technique has been used in CIS as an indicator of the risk of developing MS (Calais and colleagues. Mult Scler 2010;16:87-92).
A new study has now done the same for radiologically isolated syndrome (RIS) (Lebrun and colleagues. Rev Neurol [Paris] 2015; epublished January 19, 2015). RIS is “pre-pre-MS”, in which a person who happens to have an MRI (often for migraines) is told that they have suspicious lesions in their brain that resemble those found in MS (but have no MS symptoms). About one-third of people with RIS will develop MS symptoms over the next five years (Okuda and colleagues. PLoS One 2014;9:e90509).
The new study looked at 45 people with RIS and found that 50% had positive OCBs in their tears (55% had OCBs in their CSF). So it’s likely that many of these people with RIS will go on to develop MS.
It’s a mixed blessing being told that you have a risk of developing MS in the next few years, but this early warning does help people prepare themselves and do what they can to minimize the impact of the disease. The studies also lend weight to the idea that a sample of tears can painlessly replace a lumbar puncture.
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