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Am I sure that I have MS?
The multiple sclerosis misdiagnosis rate is around 5% and has major implications for individuals and the treatment of MS.
A case scenario
Her anger was palpable. She had been diagnosed with multiple sclerosis eight years ago and had been taking interferon-beta since her diagnosis. When I told her that I didn’t think she had MS and that her diagnosis was almost certainly complicated migraine with aura. I told her that the lesions on her MRI were nonspecific white matter lesions and not inflammatory. Her neurological examination, spinal fluid analysis and evoked potentials were normal. What clinched the non-MS diagnosis for me was the history of neurological events, which were too short-lived and migratory to be MS attacks. The final piece of the jigsaw was that a special MRI sequence showed none of her white matter lesions had a central vein, which told me that none of her white matter lesions was MS lesions.
This particular person was angry because she had decided not to start a family and had changed her career because of the fear of becoming disabled in the future and not being able to work or look after a child.
This case illustrates why I always try and review the diagnosis of patients referred to me with MS before starting a disease-modifying therapy (DMT) and why the second question on my list of questions you need to answer prior to starting a DMT concerns this issue.
Questions to ask yourself before starting a DMT
What is multiple sclerosis (MS)?
Am I sure that I have MS?
What type of MS do I have?
What prognostic group do I fall into?
What is the risk of not being treated with a disease-modifying therapy (DMT)?
Do I have active MS?
Am I eligible for treatment with a DMT?
What is the difference between a maintenance/escalation DMT and an IRT (immune reconstitution therapy)?
Do I understand the difference between short-term intermittent and long-term continuous immunosuppression?
Do I understand the concept of treat-2-target?
What are the attributes of the specific DMTs?
How can I derisk or reduce my chances of getting certain adverse events on specific DMTs?
A dirty fact
Approximately 1 in 20 people diagnosed with MS don't have MS.
Making a diagnosis of MS
Unfortunately, there is no one test that can be done to diagnose MS. MS is diagnosed by combining a set of clinical and MRI findings, electric or neurophysiological investigations and laboratory tests. If these tests fulfil a set of so-called MS diagnostic criteria the Healthcare professional (HCP) or neurologist makes a diagnosis of MS.
The underlying principle of making a diagnosis of MS is showing the dissemination of lesions in space and time and excluding other possible diagnoses that can mimic MS. The diagnostic criteria have evolved over time from being based purely on clinical attacks to those including electrical and spinal fluid tests to the modern era in which we use MRI to help confirm dissemination in time and space.
Dissemination in time means two attacks or MS lesions occurring at least 30 days apart or showing oligoclonal immunoglobulins in the spinal fluid (OCBs).
Dissemination in space means lesions occurring in different locations, for example, the optic nerve and spinal cord.
The electrical or neurophysiological tests are called evoked potential (EPs) and test electrical conduction in a particular pathway. They can be useful to show lesions in pathways that are not evident on the neurological examination or seen on MRI. The EPs can also show slow electrical conduction which is one of the hallmarks of diseases that affect myelin, the insulation of nerves that are responsible for speeding up electrical conduction.
The laboratory tests are typically done to exclude other diseases that can mimic MS. One test that is useful in helping make the diagnosis of MS is examining the spinal fluid for the presence of oligoclonal bands (OCBs), which are the fingerprint of a specific type of immune activation within the central nervous system (CNS). The OCB fingerprint is relatively specific for the diagnosis of MS in the correct clinical context. Please be aware that OCBs are found in other conditions for example CNS infections and other autoimmune diseases, but these are relatively easy to differentiate from MS.
I have spent some time explaining this all to you as we neurologists get the diagnosis wrong in approximately 5% of pwMS. In other words, 1 in 20 people who have a diagnosis of MS in life doesn't have MS when their brains are studied postmortem. This data is based on a large study that looked at the brains of all people who died with a diagnosis of MS in a region of Denmark. More recently a study from a specialist MS centre in the United States reported a misdiagnosis rate of 15% in patients with presumed MS referred to their centre for treatment.
Why is getting the correct diagnosis of MS so important? Firstly, some of the MS treatments we use have life-threatening complications; you don't want to expose people without MS to these complications. More concerning is that some of the diseases that mimic MS can be made worse by MS DMTs. Finally, a diagnosis of MS has many psychological, social, financial and economic implications for people. Just having a diagnosis of MS, even if you turn out to have ‘benign disease’, has implications for the person concerned. For example, it may affect your life choices and may impact your ability to get insurance cover to name obvious examples. I would therefore advise you to make sure you have MS and not an MS mimic.
Common MS mimics
The evolving definition of MS
Please be aware that the definition of MS is also evolving based on the diagnostic criteria we use to make the diagnosis. This means that you may have MS according to the latest diagnostic criteria when you could not be diagnosed with MS using past criteria. This diagnostic drift causes many problems for people like me who research MS, but I will discuss these issues in later newsletters.
Clinical criteria only:
Schumacher, et al. Problems of Experimental Trials of Therapy in Multiple Sclerosis: Report by the Panel on the Evaluation of Experimental Trials of Therapy in Multiple Sclerosis. Ann N Y Acad Sci 1965;122:552-68.
Clinical, EPs and CSF analysis:
Clinical, EPs, CSF analysis and MRI:
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust. The advice is intended as general advice and should not be interpreted as being personal clinical advice. If you have problems please tell your own healthcare professional who will be able to help you.