About MS

How is MS diagnosed?


Multiple Sclerosis (MS) is a complex disease and diagnosis is not always straightforward. While for some, a diagnosis can be made in a few quick steps, others can wait for a long period of further testing from the time of their first symptoms until they are officially diagnosed. This article outlines the challenges of diagnosing MS.

The complexity of MS

In MS, the immune system mistakenly attacks tissue in the brain, spinal cord and optic nerve, collectively known as the central nervous system (CNS). This occurs in localised areas in the CNS known as lesions, and can be seen in a brain scan (Magnetic Resonance Imaging or MRI).

Depending on the position of these lesions, the symptoms of MS can be very diverse. This makes the process of diagnosing MS challenging. Symptoms can typically include but are not limited to numbness, tingling, burning pain, difficulty walking, visual disturbances and fatigue.

How is MS diagnosed?

By its very name, multiple sclerosis (where ‘sclerosis’ means scarring) suggests that there are multiple lesions or scars. To clinically diagnose MS, there needs to be evidence of not only multiple attacks at different locations in the CNS, but also that these occurred at different times. While this might sound easy to determine, there is still no single clinical test to provide a definitive diagnosis. Therefore a careful combination of clinical examinations, MRI scans and lumbar punctures are required.

Methods of diagnosis

To differentiate MS from other similar neurological conditions, most neurologists use what is called the McDonald criteria. This is a published medical guide for clinicians and is periodically updated in line with the latest research and understanding of the disease (most recent update was in 2017). Put simply, the McDonald criteria require there to be a history of two or more clinical attacks/relapses with evidence of two or more MRI lesions in different areas of the brain or spinal cord. If there has only been one clinical attack (physical symptoms), then evidence of older scars or lesions in the brain (signs of previous attacks that may have been missed) can help make the full diagnosis.

A lumbar puncture that takes a sample of the cerebrospinal fluid (CSF) can also help if there has only been one clinical attack. This method helps rule out other types of infections (virus or bacteria) that may cause an immune response. If oligoclonal bands can be detected in the CSF, indicating a current or previous immune response, a diagnosis of MS can be made.

If it’s not MS, what could it be?

  • Clinically isolated syndrome (CIS)
    If the McDonald criteria are not met, maybe because there has only been one bout of neurological symptoms (lasting at least 24hrs) and only a few current lesions on the MRI scan, then the individual may be diagnosed with CIS. If more lesions appear at a later date in brain scans, or another relapse or attack of symptoms is experienced, then the individual may then be diagnosed with MS.
  • Radiologically isolated syndrome (RIS)
    In some cases, lesions might be detected if a person is having an MRI scan for another reason. If they have had no physical symptoms at all, a diagnosis of RIS might be made. Many people can have visible lesions in the brain that cause no symptoms and never lead to any disease. Only a small percentage of people with RIS will actually go on to develop MS, and more research is needed to better understand whether there are other tests that can help identify if someone with RIS might later develop MS.
  • Other conditions with similar symptoms
    A person with MS could present with a very wide range of symptoms that can also be seen in other conditions. In addition, the MRI scan may show inconclusive signs, small lesions may be missed, or the lesions can sometimes be very unusual in their shape and size, and resemble other types of brain disease or injury. Examples include:
    • Severe migraine
      People who have severe migraines are among the most common group to be misdiagnosed with MS, as their symptoms can mimic those of MS, and in some cases there may be white lesions visible in their brain scans.
    • Other autoimmune or inflammatory diseases and some brain infections
      These can also produce neurological symptoms, can show lesions in the brain MRI scan and can also produce oligoclonal bands in the CSF. Very careful analysis of the appearance of the lesions, additional blood tests or tissue biopsies and additional physical tests can help narrow down the potential diagnosis.
    • Other demyelinating diseases
      There are many diseases that result in damage to the protective covering (myelin sheath) that surrounds nerve fibres and it can be a challenge to differentiate these from MS.This can include neuromyelitis optica (NMO). NMO is a separate disease from MS, but shares several clinical features. NMO most often causes visual changes in both eyes and symptoms caused by long lesions in the spinal cord. There is a blood test that looks for specific antibodies known to be found in people with NMO which can help to clearly identify NMO. However, the absence of these antibodies does not necessarily rule NMO out. Acute disseminated encephalomyelitis (ADEM) is a brief but intense attack of inflammation in the brain, spinal cord and occasionally the optic nerve that causes damage to myelin. Symptoms of ADEM come on quickly, often beginning with behaviour changes. This condition is more common in children. There are some features of ADEM that can help to make an immediate diagnosis, but sometimes only time will tell if it was a one off attack or the first attack in a diagnosis of MS. MS Research Australia-funded researcher Dr Fabienne Brilot-Turville has been conducting research that has now made it easier to identify these types of demyelinating diseases in children and adults.


recent study published in the journal Multiple Sclerosis and Related Disorders suggests that up to 25% of people with a diagnosis of MS might be incorrectly diagnosed, highlighting the challenges faced by doctors when it comes to diagnosing MS.

In addition, some genetic disorders, copper or B12 vitamin deficiency, structural abnormalities, and other demyelinating diseases can cause neurologic symptoms that can look like MS. Some of these alternative diagnoses are easy to rule out with other medical tests, while others may require a series of additional tests or a watch-and-wait approach.

If it is MS, there are three types

Further complicating the process of diagnosis of MS, is that there are also different types of MS. They are named according to the way the disease acts on the body over time. Traditionally these have been broken down into relapsing remitting MS, secondary progressive MS and primary progressive MS.

  • Relapsing remitting MS (RRMS)
    RRMS is the most common form, with about 85% of people with MS initially diagnosed with RRMS. It is characterised by temporary periods called relapses, when flare-ups or new symptoms appear, followed by periods of recovery and remission.
  • Secondary progressive MS (SPMS)
    SPMS can later develop in some people who have initially had RRMS. In SPMS, symptoms or disability gradually worsen over time, with or without the occurrence of relapses.
  • Primary progressive MS (PPMS)
    About 10 to 15% of people diagnosed with MS receive a diagnosis of PPMS. PPMS is characterised by slowly worsening symptoms from the beginning, with few or no relapses or remissions.

Research to improve diagnosis

A diagnosis of MS is most secure if there is more than one kind of evidence, currently that includes combining clinical tests, MRI scans and lumbar punctures. Unless all of these signs are very clearly pointing to a classical diagnosis of MS, doctors may hold off on making a diagnosis until further tests or follow-up brain scans can provide more evidence. Misdiagnosing MS could put patients at risk from the side-effects of MS drugs unnecessarily, not to mention the worry and stress that can come with a diagnosis of a chronic illness. Clinicians still need to use their judgement, particularly when diagnosing MS in children or population groups where MS is less common.

Globally, there are continuing research efforts to help clinicians arrive at a diagnosis of MS as quickly and accurately as possible. MRI scanning and analysis techniques are constantly being improved. But the Holy Grail is a blood test that could swiftly confirm a diagnosis of MS. To date, while many markers in the blood have been examined and some have shown promise, there is no single blood test that can confirm MS.

In addition to the research mentioned above, other Australian researchers with early funding support from MS Research Australia, have developed a blood test that can distinguish between the different types of MS (relapsing or progressive). However, the markers used in the blood test might also be present in other types of neurological diseases, and it will still need to be combined with other tests such as MRI to confirm a diagnosis of MS. Further research is needed in this area to see if it can be used in the clinic to identify the type of MS.

More research is ongoing, which we hope will ultimately lead to a world in which MS can be identified quickly and easily, leading to its optimal treatment and management, minimising the impact of MS for everyone.

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