Case study
A young woman recently diagnosed with multiple sclerosis contacted me for legal advice. She initially presented in 2012 with optic neuritis. Her MRI was abnormal, and she was told she might develop MS. She was not offered repeat imaging and was told to return if she developed new neurological symptoms. She then went on to have a prodromal syndrome over the next ten years with chronic fatigue, intermittent abdominal pain and urinary symptoms, which were put down to co-morbid endometriosis.
She was seen in 2018 and had an MRI of her spine and was told there was no cord or nerve root compression to explain her abdominal pain. However, on reviewing the 2018 MRI report in 2022, it was not reported as being normal and stated the possibility of a suspicious lesion in the thoracic cord. The neuroradiologist had recommended repeat spinal MRI with axial or cross-sectional cuts through the thoracic cord and brain imaging. The doctor who was investigating her abdominal pain did not act on the latter.
This lady presented earlier this year with progressive right leg weakness, and MRIs of the brain and spinal cord showed multiple lesions compatible with demyelination fulfilling the criteria for dissemination in time and space. She has finally been diagnosed with secondary progressive MS and offered siponimod.
She is now seeking compensation for not being diagnosed with MS earlier, i.e. in 2012 or 2018 or sometime in between. She has been told that the diagnosis could not have been made sooner as she did not fulfil the diagnostic criteria for having MS. She disagrees and feels she should have been offered a DMT earlier.
Apparently, her current MS neurologist agrees that she did not fulfil the diagnostic criteria for having MS in 2012 or 2018 and was not eligible for DMTs.
Prof G’s opinion
St Elsewhere is a medical euphemism for a ‘fuck-up’ done under someone else’s watch, i.e. at St Elsewhere’s hospital. This is a case of St Elsewhere.
In 2012, when the patient presented, she seemed to have had dissemination in space, i.e. optic neuritis and disseminated lesions on MRI. What was missing was dissemination in time. To fulfil the latter, this patient should have been offered an interval scan say 3-6 months later, and if she had new lesions, she could have been diagnosed with MS and started on disease-modifying therapy (DMT). She should have been offered annual monitoring scans if there were no new lesions.
However, in 2012, the NHS allowed patients with CIS and high-risk scans to be offered treatment with either interferon-beta (IFN-beta) or glatiramer acetate (GA). This patient was seen by a neuro-ophthalmologist and not referred to an MSologist, which may explain why she was not offered IFN-beta or GA in 2012.
I can’t comment on why the doctor who arranged for the spine MRI didn’t take things further. The doctor was investigating her abdominal pain, and I suspect they wanted to exclude nerve root compression and were not looking to diagnose MS. However, this was a missed opportunity. If this patient had had detailed MR imaging in 2018, the diagnosis of MS would have been suspected, and she would have been referred to an MSologist who would have likely made the diagnosis of MS and started her on DMTs earlier.
This patient did not have a lumbar puncture. I think this would have been helpful to increase the diagnostic certainty and to provide prognostic information. The cerebrospinal fluid analysis helps exclude MS mimics, and the presence of oligoclonal IgG bands or OCBs can be used to confirm dissemination in time. Also, a raised CSF neurofilament level is a poor prognostic marker and would nudge you to recommend a higher efficacy treatment.
So yes, based on the facts given to me by this patient, I do think she has a legal case. If she had been offered treatment in 2012 or 2018, the treatment is likely to have delayed the worsening of her disability and the onset of the progressive phase of MS. Saying that the legal litmus test is what other clinicians were doing at the time the perceived delays were occurring. I suspect it could be argued that many neuro-ophthalmologists were not diagnosing MS or offering IFN-beta or GA in 2012, but it is difficult to argue against ignoring the recommendation of the neuroradiologist for not doing more MR imaging in 2018.
The sad thing is this case illustrates that time really is brain, or more specifically spinal cord. This patient is not alone tens of thousands of people with MS have had a delay in their diagnosis. I am sure many of you reading this newsletter could tell a similar story. I am interested to hear your stories. Please don’t be shy.
MS Diagnosis
I want to remind you that even if you have been diagnosed with MS, you may not have MS. In the study below, approximately 1 in 5 people diagnosed with MS didn’t. This figure is much higher than in previous studies. I have always quoted the Danish post-mortem studies that suggest that about 1 in 20 patients are misdiagnosed. Maybe Danish neurologists are better at diagnosing MS compared to their American colleagues.
No single diagnostic test can 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 diagnoses MS.
The underlying principle of diagnosing MS is to show the dissemination of lesions in space and time and to exclude other possible diagnoses that can mimic MS. The diagnostic criteria have evolved 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 at least two attacks or two MS lesions occurring at least 30 days apart.
Dissemination in space means lesions occur in different locations, such as the brain stem and spinal cord.
The electrical or neurophysiological tests are evoked potential (EPs) and test electrical conduction in a particular neuronal pathway. They can help show the effects of lesions in pathways that are not evident on neurological examination or seen on MRI. The EPs can also demonstrate slow electrical conduction, one of the hallmarks of diseases that affect myelin, the insulation of nerves 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 diagnosing MS in the correct clinical context. Please note OCBs can be found in nervous system infections and other autoimmune diseases. Therefore, the finding of OCBs is not diagnostic on its own.
When CSF is sent to the laboratory, they measure the protein, glucose, and lactose and do a cell count. The cells in the CSF are also examined to ensure they are not abnormal.
Why is getting the correct diagnosis of MS so important? Firstly, some 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 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 have benign MS in the future, has implications for the person concerned. For example, it may affect your life choices and your ability to get insurance coverage, to name two obvious examples. I would, therefore, advise you to make sure you have MS and not an MS mimic.
The most common MS mimics are:
Cerebrovascular disease
Acute disseminated encephalomyelitis or ADEM
Neuromyelitis optica or NMO
Behcet’s syndrome
Migraine
Sarcoidosis
SLE or systemic lupus erythematosus
Antiphospholipid antibody syndrome
Leukodystrophies
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 fulfil contemporary McDonald Criteria and had a more likely alternate diagnosis.
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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 and should not be interpreted as personal clinical advice. If you have problems, please tell your healthcare professional, who will be able to help you.
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