What, I don’t have MS?

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In the study below approximately 1 in 5 people diagnosed with MS don’t have MS. This is so much higher than previous studies. I have always quoted the Danish post-mortem studies that sugget only 1 in 20 MSers are misdiagnosed. Maybe Danish neurologists are simply better at diagnosing MS compared to their American colleagues?


There is no one test that can be done to diagnose MS. MS is diagnosed by combing 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 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 to attacks or MS lesions occurring at least 30 days apart. 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 the effects of lesions in pathways that are not evident on 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 to make the diagnosis of MS is examining the spinal fluid for the presence of oligoclonal immunoglobulin G or IgG 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 note OCBs can are found in infections of the nervous system and other autoimmune diseases, therefore, the presence of OCBs are not diagnostic on their own.

I have spent some time explaining this all to you as we neurologists get the diagnosis wrong in approximately 5% of the time and if this paper below is correct may be in even a higher number of patients. In other words, at least 1 in 20 people who have a diagnosis of MS in life don’t have MS when their brains are studied at postmortem.

Why is getting the correct diagnosis of MS so important? Firstly, some of the treatments for MS have life-threatening complications; you don’t want to expose people without MS to these complications. Some diseases that mimic MS can be made worse by MS DMTs. This latter is particularly relevant for NMO or neuromyelitis optic. Patients with NMO misdiagnosed as having MS get worse on many of the 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 on your ability to get insurance cover to name to obvious examples. I would, therefore, advise you to make sure you have MS and not an MS mimic.

The most common MS mimics:

  1. Cerebrovascular disease
  2. Acute disseminated encephalomyelitis or ADEM
  3. Neuromyelitis optica or NMO
  4. Behcet’s syndrome
  5. Migraine
  6. Sarcoidosis
  7. SLE or systemic lupus erythematosus
  8. Antiphospholipid antibody syndrome
  9. Leukodystrophies

The evolving definition of MS based on diagnostic criteria:

Clinical criteria only:

  1. 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:

  1. Poser, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983;13:227-31.

Clinical, EPs, CSF analysis and MRI:

  1. McDonald, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001;50:121-7.
  2. Polman, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 2005;58:840-6.
  3. Polman, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69:292-302.
  4. Thompson et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb;17(2):162-173.

Kaisey et al. Incidence of multiple sclerosis misdiagnosis in referrals to two academic centers. Mult Scler Relat Disord. 2019 May;30:51-56.

BACKGROUND: Multiple Sclerosis (MS) specialists routinely evaluate misdiagnosed patients, or patients incorrectly assigned a diagnosis of MS. Misdiagnosis has significant implications for patient morbidity and healthcare costs, yet its contemporary incidence is unknown. We examined the incidence of MS misdiagnosis in new patients referred to two academic MS referral centers, their most common alternate diagnoses, and factors associated with misdiagnosis.

METHODS: Demographic data, comorbidities, neurological examination findings, radiographic and laboratory results, a determination of 2010 McDonald Criteria fulfillment, and final diagnoses were collected from all new patient evaluations completed at the Cedars-Sinai Medical Center and the University of California, Los Angeles MS clinics over twelve months.

RESULTS: Of the 241 new patients referred with an established diagnosis of MS, 17% at Cedars-Sinai and 19% at UCLA were identified as having been misdiagnosed. The most common alternative diagnoses were migraine (16%), radiologically isolated syndrome (9%), spondylopathy (7%), and neuropathy (7%). Clinical syndromes and radiographic findings atypical for MS were both associated with misdiagnosis. The misdiagnosed group received approximately 110 patient-years of unnecessary MS disease-modifying therapy.

CONCLUSION: MS misdiagnosis is common; in our combined cohort, almost 1 in 5 patients who carried an established diagnosis of MS did not fulfill contemporary McDonald Criteria and had a more likely alternate diagnosis.

About the author

Gavin

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

11 comments

  • Can someone with a misdiagnosis of MS relapse more than once?

    If so, the efficacy of all drugs has to be adjusted (i.e. haircuted) by 5 to 20 per cent.

  • In your list of MS mimics, what about Lyme disease? I see it frequently mentioned as having very similar symptoms and I don’t see it on your list.

    • Lyme disease is a very rare mimic of MS and usually has a characteristic clinical presentation that allows one to differentiate it from MS. If you do an LP as part of the work-up it is very active in Lyme disease compared to MS. In my experience, it is not a problem.

      Please note chronic Lyme disease affecting the CNS is extremely rare and many of us doubt whether or not it exists after the treatment of acute Lyme disease.

  • I find this interesting. My experience is from the other side, being misdiagnosed with Chronic Fatigue Syndrome for many years. Interesting that it’s not on the list. I wonder why?

    CFS and MS have a lot of the same symptoms. Basically, take CFS and add urge incontinence, optic neuritis, and numbness, and it’s MS.

    Another big difference is MS is neurodegenerative, and in my case relapsing/remitting, whereas CFS can stay the same or totally go away.

    Also, there are no tests for CFS, or a known cause, or treatment. It is meant to be diagnosed by symptoms, and by ruling out everything else. That isn’t what happened in my case, the NHS refused for years to let me see a neurologist or have any neurological tests. I was given blood tests and misdiagnosed at a hospital by a specialist in infectious diseases. Even though CFS is, rightly or wrongly, categorised as a neurological illness by the World Health Organisation.

    My own research told me that I probably in reality had MS. And I eventually, far too late, gave up on the NHS, saw a neurologist privately, put it on credit card, and was diagnosed within a few months as having MS. The MRI scan shows that I have so many brain lesions my brain looks like Swiss cheese, the evoked potential tests showed my eyes are permanently damaged by the Optic Neuritis, and the lumber puncture showed IgG bands. So I am very confident that MS is the correct diagnosis. Not because I have any faith left in doctors, but because it totally fits the symptoms I have been living with for decades. Since I was an adolescent.

    Had I not given up on the NHS in 2017, I would have died still misdiagnosed as being mentally ill with CFS, because no one would believe me.

    As for how people are misdiagnosed with MS, that’s hard for me to imagine, it was such a hard diagnosis for me to get. I know people who have the symptoms, and get to see all the specialists, have all the tests, and nothing is found.

    In my case I had very obvious MS and every test was positive, but the NHS was utterly dedicated to the belief that I wasn’t physically ill. That I was imagining it all, it was all my fault, and if I just tried harder it would go away. They made me hate myself for ‘pretending’ to be ill. For just being lazy.

    MS is a terrible disease, but it’s a massive relief to me, getting the correct diagnosis. It being accepted that I’m physically ill. It really scares me, the thought that the next neurologist I see might take that away.

    Because I’m finally on treatment for symptoms. Pain, vertigo/nausea/motion sickness, etc, and I’m on Modafinil, which is awesome. And although the NHS has robbed me of decades of my life, a lot of my functioning, and a lot of my brain, there is now the possibility of treatment. Lemtrada, Ocrevus, HSCT…

    My neurologist warned me that I might die from the treatment, but I said it’s okay. I’ve been so sick, for so long, I’ll risk it. It’s so strange, going from the NHS telling me I was making it all up for decades, to offering me chemo for it. Which I was too sick have. And the lack of a history of MRI scans, or trying multiple disease modifying medications, means I’m having trouble fitting criteria. But I’m not dead yet, and I have done really well to survive and get this far. It’s amazing I’m not dead yet, and I’ve proved everyone wrong.

    That dozens of medical professionals in the NHS over decades were so wrong about me, still astounds me. And that I was right. Because I shouldn’t have been. I’m working class, uneducated, traumatised, and severely physically and mentally disabled. But I was right about everything. I suppose I find it hard to imagine people being misdiagnosed with MS, because there are tests. Not definitive I know, but still. One would imagine the tests would have had to show something. At least be borderline.

    Some doctors very wrongly think that patients are fine until they get a diagnosis. But, no. We’re already living with the symptoms. So I understand why patients would grasp onto whatever diagnosis they can get. Because as terrible as MS is, what the NHS did to me was worse.

    Anyway, I’m seeing prof G at the end of this month. London here I come. So I shall see what happens…

    • People presenting with CFS and have MS typically go onto to develop new symptoms that lead to the diagnosis of MS.

      <5% of patients with CFS will go onto to develop MS.

      Unfortunately, CFS is a bit of a dumping ground with a large number of patients being labelled as having CFS when in fact they have another underlying cause/diagnosis that would account for their fatigue. The commonest is depression.

      • I could have written that post myself. I was mid diagnosed as having CFS too for many years and saw many neuros (including you Gavin!) my tests apart from a couple of lesions were normal and I’d had glandular fever twice. I had a relative with MS so I was labelled as a patient who believed I had MS but in reality didn’t. I went to counselling, graded exercise etc etc then my disease after 13 years got worse and the sensory relapses I had suffered with for years finally led to more brain lesions, positive oligoclonal bands, spinal lesions etc. I am finally believed!!! What a nightmare. Since my first symptoms at 17 and my diagnoses at 30, I’m 41 now and I have it under control with rituxan and better health food choices. But yes I think there are many patients out there being labelled as having CFS or conversion disorders who actually have MS. If a patient presents with MS type symptoms but the tests are not representative of MS, please don’t discharge them or insist they have depression! believe them and let them know that sometimes it takes a while for the tests to show up like in my case and save them from the hell I went through (I saw 4 MS specialists privately who all said it wasn’t MS)

      • CSF is getting acknowledged as a real physical disease -possibly mitochondria related and not autoimmune (as the trial for CFS and Rituxan failed) and of course not psychological. Hopefully soon there will be biomarkers and tests to distinct this debilitating disease because it tends to be given too easily to patients with fatigue.
        I assume NFL will be added in the future McDonald criteria, so less misdiagnosis’ (even if Nfl is not MS specific either).

    • No. But it is a good negative predictor of MS, i.e. if you doubt the patient has MS and they have a negative CSF this helps you not make the diagnosis of MS.

      Please note not making a diagnosis of MS is as important as making the correct diagnosis.

      About 2% of people who fulfil the McDonald criteria for having MS will be OCB negative. Do these people have MS? When you re-LP them 6 or more months later about 50% will now have OCBs. So being OCB negative needs to carefully considered.

      • So does this mean pwMS may fluctuate between OCB negative and OCB positive? Depending on some factors… It’s a case of hit or miss when the LP is done?

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