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:
- Cerebrovascular disease
- Acute disseminated encephalomyelitis or ADEM
- Neuromyelitis optica or NMO
- Behcet’s syndrome
- SLE or systemic lupus erythematosus
- Antiphospholipid antibody syndrome
The evolving definition of MS based on diagnostic criteria:
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:
- 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:
- 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.
- Polman, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 2005;58:840-6.
- Polman, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69:292-302.
- 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.
13 thoughts on “What, I don’t have MS?”
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.
Yes, this is why the misdiagnosis rate is high. This is a particular problem for migraine and vascular disease.
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.
Is the absence of OCBs diagnostic on its own?
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?
I have the same question! Perhaps even more specifically: given that:
(1) the OCBs are the result of inflammation (is my assumption correct here?), and
(2) the CSF has a high turn-over rate (the entire volume of fluid gets replenished every 12 hours or so, correct?), and
(3) in progressive MS, inflammation is often no longer in the central nervous system (eg, it “burned out” some years ago), then:
would we not expect the majority of progressive MS patients to be OCB negative? Have there been studies to address this question? All that I ever see are statistics for the entire MS population that conclude 95% of MS patients are OCB positive. I’ve never seen a study that focuses on that 5% remaining population … do they all have progressive forms of MS, where neurodegeneracy has superceded inflammation as the primary driver of continuing disability? Also, do the OCBs disappear in an RRMS patient during a long remission period?
Tbh I’ve always queried my diagnosis as I only just scrape in to the revised McD criteria 2017. I’ve positive OCBs, 1-2 brain lesions suspicious of demyelination (reported as non-specific white matter lesions) and a subtle change on my c spine (previously not identified but apparently there since my 1st MRI). My initial presenting symptoms were altered sensations in my arms and legs. I now get painful throbbing and stiff legs especially when I’m cold and a numb bum sometimes. My case has been discussed a 2 MDT meetings so I don’t feel that I can ask for another opinion. What muddies the waters is that my Mum has MS and I had an episode of pins and needles in both lower legs in 1999. At that time, I only had a lumbar spine MRI but didn’t know this until my recent symptoms. My neurologist isn’t ruling this out as my 1st relapse but I said you can’t rule it in either.
All of this has got my on ocrelizumab so let’s hope I am not the 1 in 5 who doesn’t have MS ☹️😢
For someone who having symptoms and is concerned it’s MS how often shout you repeat a MRI to be sure it’s not?
Also can you book to see you privately or if not please recommend a MS specialist who is top of the field too.