Tag Archives: mimic

Diagnosis, Stages of MS

What should I expect during the diagnostic consultation?

The practice of neurology and medicine varies worldwide, so I will explain what to expect if you were to consult me. 

Key points

  • The principles of diagnosing MS are to show the dissemination of lesions in space and time and to exclude alternative diagnoses that mimic MS.
  • Diagnosing MS takes time and should not be rushed; do not be afraid to ask questions.
  • Most patients diagnosed with MS have an emotional response similar to the five stages of grief – Denial, Anger, Bargaining, Depression and Acceptance (DABDA). Additionally, many patients experience Anxiety about the future (DABDA+A).
  • Newly diagnosed patients should avoid overloading themselves with information about MS; much of the online information can be misleading and anxiety-provoking. Guidance is provided below about reliable information sources.
  • Counselling, cognitive behavioural therapy and the support of an MS ‘buddy’ can help patients adjust to a diagnosis of MS, which is a serious condition and should be respected.
  • You should be aware that medical ‘gaslighting’ may happen and know how to deal with it.

Tests to exclude other diagnoses

MS is a clinical diagnosis and a diagnosis of exclusion. Therefore, I would take a detailed medical and neurological history and examine you for neurological signs. Finding signs of involvement in a particular neurological pathway is important for fulfilling the criteria for dissemination in space. MS must involve at least two neuronal pathways. To be confident that no alternative diagnosis could explain your presentation, a full work-up will likely include magnetic resonance imaging (MRI) of the brain and spinal cord, evoked potentials, a lumbar puncture and blood tests. In addition, I would need to show dissemination in time, involving two or more structures separated in time by at least 4 weeks.

The diagnosis of MS is not trivial and should not be rushed. If I doubted the diagnosis, I would wait. The old maxim ‘time is often the best diagnostician’ is as pertinent today as it was in the past. Despite this, the misdiagnosis rate remains stubbornly high. I recommend you read some of the posts that cover the diagnosis of MS in more detail, such as Am I sure that I have MS? and Do I have active MS?

Time to adjust to a diagnosis of MS

You should not expect too much from the initial consultation. The second consultation, once all the diagnostic tests are back, will be the difficult one. Before COVID-19, an MS diagnostic workup in the NHS would take about 6 ̶ 8 weeks. Due to COVID-19-related delays in getting MRI scans and evoked potentials, it currently takes up to 4 months. Occasionally, patients with possible MS are admitted to the hospital because of a disabling attack. This allows us to make a more rapid diagnosis. 

Being diagnosed with MS or any other chronic and potentially disabling disease is distressing. In my experience, patients’ responses are highly variable, including relief about finally getting a diagnosis, surprise, shock, anger or blaming the messenger for the bad news. Some question my judgement and refuse to accept the diagnosis; they may accuse me of being wrong and seek a second, third or fourth opinion. Many are devastated and expect the worst: how long before I need a wheelchair? Rarely patients are uninformed, have little or no idea about MS and ask about the disease. 

Examples of some responses to a diagnosis of MS

I always try and be reassuring and tell patients that MS is now a treatable disease. If we manage their MS actively, we can prevent or at least delay the development of disability for many decades.

Emotional response

I also warn patients about the emotional reaction they will likely have to being diagnosed with MS. The psychological impact of an MS diagnosis and the uncertainty associated with having a potentially disabling disease should never be underestimated. Elisabeth Kübler-Ross in 1969 described five common stages of grief, best known by the acronym DABDA:

Denial, Anger, Bargaining, Depression, Acceptance

We have added an extra A – for Anxiety about the future – to expand this to DABDA+A. People diagnosed with MS may go through these stages in order of the pneumonic, but some will jump around, and others go through some stages many times. Although the Kübler-Ross stages have been criticised in the psychological literature, they provide a valuable framework for discussing a patient’s emotional journey. Being diagnosed with MS is a marathon, not a sprint, and it will take time to come to terms with it.

It is important for healthcare professionals (HCPs) to be there for the journey and to make sure that newly diagnosed patients have access to their MS team and high-quality information about MS. 

Step-wise approach to understanding MS

In the modern era, most patients I diagnose as having MS are aware of the disease and suspect they have MS before I tell them so. I say this because Dr Google, Dr ChatGPT and Dr Bing are only keystrokes away, and their answers are very credible. 

Because of their anxiety, most newly diagnosed patients only take away one thing from the consultation: they have MS.  Almost everything else they hear is forgotten. I encourage patients to record the consultation or bring a partner, friend or family member who can be their backup memory. 

I try to avoid overloading patients with information early on. Instead, I provide links to online resources about having MS. We arrange a follow-up session with the MS nurse specialist in the next 10 ̶ 14 days so that they can ask questions.

Guidance about what information to trust

I counsel patients to stay away from Dr Google, Dr ChatGPT and Dr Bing until they have come to terms with having MS. Much of the MS-related content available on the web is misinformation and disinformation; until you understand the disease, it is difficult to know what information is valid, reliable and helpful and what is quackery. Many patients ignore this advice and overwhelm themselves with information, which can worsen anxiety. 

I don’t introduce recently diagnosed patients to MS-Selfie initially. MS-Selfie is written at too high a level for the average person who is newly diagnosed. If patients want more information, I direct them to the MS Trust, the MS Society and ‘MS Brain Health: time matters’ (for more detail, see Resources and hot topics).  

Counselling, support and respect

Depending on a patient’s response to the diagnosis, we may refer them for counselling, cognitive behavioural therapy and/or mindfulness therapy to help them come to terms with having MS and to help manage their anxiety. Most patients are receptive to these psychological therapies. 

Many people with MS are traumatised by their diagnostic consultation and may experience symptoms of post-traumatic stress disorder from the event. This should not happen in the modern era. In my experience, gestures such as having tissues on hand for a distressed patient or holding their hand are ways that HCPs can demonstrate their empathy.

On rare occasions, particularly for patients who are alone and socially isolated, we may buddy them up with another carefully chosen patient to ask questions and learn about MS. These MS buddies need to be optimistic, able to communicate well and not overwhelm the recently diagnosed patient with information. I work closely with the charity Shift.ms, which does a similar thing. 

In the diagnostic consultation, I avoid too much detail about treating MS and the specific DMTs. These are best discussed at the next visit. With some patients, however, the discussion gets to treatments very quickly. In such cases, I tailor the consultation to the individual’s needs. 

During the diagnostic consultation, I also show patients their MRI scans. Seeing your brain, spinal cord and MS lesions provides an objective way of helping you to visualise the disease. 

Recently diagnosed patients must be given time to ask questions and even to sit in silence. MS is a serious disease, and informing someone about the diagnosis must be done carefully. After more than 30 years as a neurologist, I still find telling my patients they have MS challenging. The patient being diagnosed with MS, as well as the disease, must be respected. 

What if a doctor belittles my concerns?

The term ‘medical gaslighting’ describes a scenario where health professionals dismiss or downplay a patient’s real symptoms, leading to an incorrect diagnosis. Now that we have recognised medical gaslighting as a significant problem in MS, please don’t allow a neurologist to gaslight you. There are things you can do to prevent this. 

  • Keep detailed notes and records. Patient-held notes transform consultations and allow you to become a partner in your healthcare.
  • Ask to record the consultation. Many HCPs don’t like this; just tell them you must listen to the conversation again to ensure you don’t forget things or miss important information. You will be surprised how this changes the HCP’s behaviour. 
  • Ask questions. Then ask some more. And don’t be fobbed off; if you are dissatisfied with the answer, ask the question again. 
  • Take someone with you for support. Having a witness during the consultation has a similar effect to recording the conversation or documenting it with notes. 
  • Focus on your most pressing issues to make the best use of your consultation time. If your HCP is pressed for time, say you understand, but you would like to prioritise the following issues today. This helps you to frame the limits of the consultation and promote a two-way discussion. Also, don’t expect the HCP to have all the answers at their fingertips, but do expect them to come back to you later with the answers.
  • Try and pin down the next steps for your problem; ask what the action points are. For example, if the MRI shows this, how will that change my management? Do I need further investigations? How soon should I switch treatments?

If you still feel that you are being ignored, here are some of your options.

Some courses of action open to you if you experience medical gaslighting.

Abuse, manipulation, gaslighting and delaying a diagnosis are potentially reportable events which HCPs need to know about. Therefore, make your healthcare system aware of the problem rather than suffer in silence. 

Pregnancy and childbirth, Women's health

Managing MS during pregnancy

Opinion on how MS impacts pregnancy is based largely on data that predate the current era of active treatment and the newer generation of disease-modifying therapies (DMTs). In this section I have therefore addressed many of the important issues that women who are considering pregnancy need to understand, including:

  • the effect of pregnancy on the course of MS
  • how to manage relapse during pregnancy
  • the role of naturally occurring interferon-beta and its possible implications for women with MS taking therapeutic interferon-beta
  • management of MS symptoms and morning sickness during pregnancy
  • the crucial issue of DMT safety and possible teratogenic effects on the developing foetus.

Will pregnancy affect the course of my MS?

Yes, pregnancy effects on MS have been observed at a group level, though it is difficult to notice changes in individuals. It is well known that MS attack rates drop during the second and third trimesters of pregnancy and relapses rebound again in the first 6 months after delivery. However, only a minority of women with MS have post-partum relapses. Breastfeeding may blunt the post-partum rebound, but this is not absolute. Therefore, most neurologists now recommend starting or restarting DMTs soon after delivery to try and prevent post-partum relapses.

At a population level, the more children you have, the better your overall prognosis. This effect is small and is based on studies done in the pre-DMT era. It may be due to the immunological effects of pregnancy that work like a DMT in MS. Immunologists have tried to understand this phenomenon in the hope of developing treatments for MS that mimic the pregnancy state.

How is a relapse managed during pregnancy?

In the event of having a relapse during pregnancy, a short course of high-dose corticosteroids can be considered. However, I limit using steroids to disabling and/or severe relapses, especially early in the first trimester, as there is a small risk of orofacial abnormalities (cleft lip and palate) and reduced birth weight from exposure of the developing foetus to high-dose steroids. There is also a risk of precipitating gestational diabetes in women receiving high doses of steroids during pregnancy. In the rare situation of a severe relapse unresponsive to high-dose steroids, plasma exchange may need to be considered.

Could neutralising antibodies to therapeutic interferon-beta affect my baby?

Naturally occurring interferon-beta is a cytokine (cell-signalling agent) produced by the body to help fight infections. As there is only one human interferon-beta, antibodies to therapeutic interferon-beta (IFN-beta) will neutralise the body’s own natural interferon-beta. If you are taking IFN-beta for your MS, there is thus a theoretical risk that neutralising antibodies (NABs) to the DMT might cross the placenta and affect the role of human interferon-beta in foetal development.

Interferon-beta is important for innate immunity and neutralising your own interferon-beta may put you at risk of getting viral infections. Interferon-beta also plays a role in foetal bone development, but the placenta does not mature in relation to immunoglobulin transfer until near the end of the second trimester of pregnancy, so it is unlikely that sufficient NABs cross the blood ̶ placental barrier to affect foetal bone development. However, in the third trimester, NABs will cross over the placenta into the foetal circulation and may impact the baby’s innate immunity. Despite these theoretical concerns, there is no indication from published data to support these potential adverse effects of NABs on IFN-beta.

If I fall pregnant while on a DMT, will this affect the baby?

This depends on which DMT you are taking and what you mean by ‘affecting the baby’. We worry most about teratogenic effects, which describe congenital malformations. Teriflunomide, S1P modulators and cladribine are generally classified as drugs that may be teratogenic, and hence precautions need to be taken so as not to fall pregnant on these agents. Foetal malformations usually occur very early in foetal development, often before the woman knows she is pregnant; therefore, it is difficult to do anything about it once foetal exposure occurs. Despite this, even for women who are on these agents and fall pregnant, we don’t automatically recommend termination of pregnancy. We refer them to the high-risk pregnancy clinic to discuss the options with an obstetrician. Many women continue their pregnancies with an uneventful outcome and a normal baby. On the other hand, some women choose the option of terminating their pregnancy.

A large amount of data from MS pregnancy registries and post-marketing surveillance indicates no increased risk of major congenital anomalies or spontaneous abortions (miscarriages) after exposure to interferon-beta or glatiramer acetate. Most neurologists are, therefore, comfortable with their female patients falling pregnant on these agents, continuing the treatment through pregnancy and then breastfeeding their babies.

Fumarates (dimethyl fumarate [Tecfidera], diroximel fumarate [Vumerity]) are not teratogenic and are unlikely to have a negative impact on pregnancy outcomes. We need more data from registries and post-marketing surveillance before we can be confident that the fumarates are safe during pregnancy. However, these agents are prodrugs and converted to monomethyl fumarate, which is part of our metabolism, so it is very unlikely that the fumarates will cause problems. I don’t have an issue with women falling pregnant on the fumarates and continuing them through pregnancy, but there is conflicting advice about this.

Should I continue taking drugs for my MS symptoms during pregnancy?

Yes and no. It depends on what the medications are for and whether they are safe during pregnancy. Ideally, you should wean off any symptomatic therapies or at least change to alternative medications that are safe to take during pregnancy. It is important to try and plan your pregnancy and if necessary be referred to a special medical pregnancy clinic so that these issues can be addressed. Many women with MS find that their MS-related symptoms improve during pregnancy, and they can do without symptomatic therapies. However, unless you are prepared to wean yourself off symptomatic therapies you won’t know.

Physical therapies should be continued during pregnancy. One could argue that everyone with MS should be physically active and do pelvic floor exercises. Pregnancy and childbirth may impact bladder and bowel function, so it is important to see a pelvic floor therapist to start pelvic floor exercises. The latter are taught to women in antenatal classes.

How do you treat morning sickness or hyperemesis gravidarum during pregnancy?

Treating morning sickness or hyperemesis gravidarum is no different in women with MS than in the general population. It involves hydration, vitamin supplements (in particular, thiamine) and the judicious use of antiemetics (for example, cyclizine, prochlorperazine, promethazine, chlorpromazine, metoclopramide and domperidone). If the vomiting extends into the second trimester, ondansetron can be used. In very severe cases of morning sickness, steroids may be required; for example, hydrocortisone 100 mg twice daily can be converted to prednisolone 40 ̶ 50 mg daily by mouth, which can then be tapered to the lowest level that still controls symptoms. For patients taking a fumarate, try and take your medication later in the morning when you are less likely to vomit.

What dose of vitamin D do you advise during pregnancy?

During pregnancy vitamin D requirements are increased and I recommend doubling the dose for supplementation from 4,000 IU of vitamin D3 to 8,000 IU per day. At the same time, women who are pregnant should be on iron and folate supplements that should ideally be started before falling pregnant.

References

Krysko KM et al. Treatment of women with multiple sclerosis planning pregnancy. Curr Treat Options Neurol 2021;23:11.

Other articles in this series on Pregnancy and childbirth
Planning for pregnancy
Preparing to give birth
Breastfeeding if you are on a DMT
Concerns about parenting

Diagnosis

Am I sure that I have MS?

The multiple sclerosis misdiagnosis rate is around 5% and this has major implications for individuals and the treatment of MS.

Key points

  • A wrong diagnosis of MS may have financial, social and psychological consequences for the individuals concerned, affecting major life decisions.
  • Some MS treatments have life-threatening complications and should only be prescribed for people with a clear diagnosis of MS.
  • Some of the diseases that mimic MS can be made worse by disease-modifying treatments for MS.
  • Diagnostic criteria for MS have evolved and now take account of clinical, electrical, laboratory and magnetic resonance imaging findings.

A case study

She had been diagnosed with multiple sclerosis 8 years ago and had been taking interferon-beta since her diagnosis. I told her that I didn’t think she had MS and that her diagnosis was almost certainly complicated migraine with aura. The lesions on her magnetic resonance imaging (MRI) scan were non-specific white matter lesions and not inflammatory. Her neurological examination, spinal fluid analysis and evoked potentials (EPs) 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 an MS lesion.  Her anger was palpable. She 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 to review the diagnosis of patients referred to me with MS and why it is important to answer this question before starting a disease-modifying therapy (DMT).   

Making a diagnosis of MS

Unfortunately, there is no single test to diagnose MS. Rather, MS is diagnosed by combining a set of clinical and MRI findings, electrical 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 principles of diagnosing MS are to show the dissemination of lesions in space and time and exclude possible mimics of MS. The diagnostic criteria have evolved over time from 1) being based purely on clinical attacks,1 to 2) include electrical and spinal fluid tests as well as clinical attacks,2 and 3) to add on the use of MRI to help confirm dissemination in time and space.3–6  

Dissemination in time 

This means that two attacks or MS lesions must occur at least 30 days apart or that oligoclonal bands (OCBs) of immunoglobulins can be detected in the spinal fluid.

Dissemination in space 

This requires MS lesions to occur in different locations, for example, the optic nerve and the spinal cord. 

Electrical tests

The electrical or neurophysiological tests are called evoked potential (EPs) and test electrical conduction in a particular pathway. They can show lesions in nerve 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 around nerves that is responsible for speeding up the electrical conduction of nerve impulses.

Laboratory tests

The laboratory tests are typically done to exclude other diseases that can mimic MS. Examining the spinal fluid for the presence of OCBs is useful in helping to make an MS diagnosis. OCBs 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. (OCBs are also found in CNS infections and other autoimmune diseases, but these are relatively easy to differentiate from MS.)

Please be aware that you may have MS according to the latest diagnostic criteria when you could not be diagnosed with MS using past criteria.

Why is a correct diagnosis important?

Neurologists get the diagnosis wrong in approximately 5% of people with MS. In other words, one in 20 people who have a diagnosis of MS in life does not have MS when their brain is studied post mortem. This data is based on a large study in a region of Denmark.7 More recently, a study from a specialist MS centre in the United States reported a misdiagnosis rate of approximately 15% in patients with presumed MS referred to their centre for treatment.8 

Why is getting the diagnosis of MS correct so important? Firstly, some MS treatments 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. Even if you turn out to have ‘benign disease’, just having a diagnosis of MS, has implications for your life choices and may impact your ability to get insurance cover, to name obvious examples. I, therefore, advise you to make sure you have MS and not an MS mimic.

Common MS mimics

References

  1. Schumacher GA, 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.
  2. Poser CM, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983;13:227–31.
  3. McDonald WI, 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.
  4. Polman CH, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 2005;58:840–6.
  5. Polman CH, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011;69:292–302.
  6. Thompson AJ, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 2018;17:162–73.
  7. Engell T. A clinico-pathoanatomical study of multiple sclerosis diagnosis. Acta Neurol Scand 1988;78:39–44.
  8. Kaisey M, et al. Incidence of multiple sclerosis misdiagnosis in referrals to two academic centers. Mult Scler Relat Disord 2019;30:51–6.