Tag Archives: neurologist

Cognition and mental health

Management of mental health disorders in people with MS

Emotional problems in people with MS must be recognised, addressed and treated, rather than dismissed as an inevitable consequence of living with this chronic condition.

Key points

  • An MS diagnosis naturally triggers emotions similar to the stages of grief (denial, anger, bargaining, depression, acceptance); in addition, the unpredictability of MS causes anxiety in many patients.
  • Anxiety, often combined with depression, is linked to a poorer quality of life, cognitive dysfunction, increased risk of suicide, and significant occupational and social problems.
  • Emotional problems in MS are typically exacerbated by fatigue, pain and poor sleep – all of which interfere with therapy and lifestyle adjustments.
  • Emotional changes in MS require treatment, just as physical symptoms do. This should comprise routine screening, targeted drug treatment and structured psychological and behavioural therapies.
  • Motivational coping styles that involve direct problem-solving and active participation in treatment planning (i.e. self-management) help people with MS adjust to their diagnosis.
  • Avoidance coping strategies generally lead to poorer psychological outcomes.
  • The presence of social support is a critical protective factor.

Impact of emotional changes

Emotional disorders have an adverse effect in people with MS, potentially impairing their ability to cope with disability and reducing overall health-related quality of life. Living with MS can also adversely affect relationships, for complex reasons, including both emotional and physical problems associated with the disease. Therefore, such symptoms must be recognised, addressed and treated, rather than dismissed as an inevitable or acceptable consequence of living with a chronic condition such as MS.

Emotional disturbances in people with MS may be reactive, i.e. a natural, adaptive psychological response to being diagnosed with a long-term, unpredictable and potentially disabling disease. Common emotions include grief, sadness, worry, fear, irritability and moodiness. Elisabeth Kübler-Ross in 1969 described five common stages of grief, best known by the acronym DABDA. We have added an extra A, for Anxiety about the future, to include the emotional reaction to a diagnosis of MS. The expands the mnemonic to six stages: DABDAA.

Denial, Anger, Bargaining, Depression, Acceptance, Anxiety

These emotional stages are considered ‘normal’ and an understandable coping mechanism. As with grieving, if they are prolonged, dominant and impact your social and occupational functioning, they are considered abnormal and require intervention. Remaining angry, resentful and depressed for decades will negatively impact your functioning. 

Anxiety and depression in MS

Anxiety affects people with MS with a frequency often matching or exceeding that of depression. The highest prevalence of anxiety is observed in people with MS with low physical disability, defined by an Expanded Disability Status Scale (EDSS) score of less than 3.0. This finding suggests that anxiety is driven less by accumulated physical deficit than by the psychological factors of worry, fear and the inherent unpredictability of MS.

Maladaptive coping strategies are strongly associated with an increased risk of developing mood symptoms. A tendency to use avoidance coping – disengaging from problems rather than confronting them – is a significant predictor of poorer psychological outcomes. Similarly, psychological traits such as low optimism or a less positive attitude can heighten the risk of anxiety.

For a significant subset of patients, MS may first present not to a neurologist, but to a primary care physician, a therapist or a psychiatrist, with symptoms of anxiety or depression. Because the symptoms are psychiatric, the underlying neurological cause is not yet suspected.

Quality of life and daily functioning

Anxiety is a major contributor to the overall disease burden of MS, affecting nearly every aspect of life. Studies show that anxiety, often combined with depression, is linked to a poorer quality of life, cognitive dysfunction, increased risk of suicide, and significant occupational and social problems.

The impact of anxiety on many of the most challenging symptoms of MS – notably fatigue, pain and sleep problems – may be greater even than the effect of depression.  MS symptoms can trigger or worsen anxiety, and the resulting anxiety intensifies the perception and severity of those same symptoms, thus creating a negative feedback loop.

Damaging health behaviours linked to undiagnosed and untreated anxiety can further compromise a patient’s well-being. For example, alcohol and substance abuse, as well as smoking, not only have their own intrinsic health risks but can also interfere with MS management and adherence to treatment. 

Anxiety as a reaction to living with MS

The direct impact of the disease on the brain’s emotional circuits occurs in parallel with the profound psychological and existential challenges of living with MS. Even in the absence of any direct neurological damage to mood-regulating centres, the lived experience of MS itself provides rationale for the development of severe anxiety. 

The unpredictability of the disease and the constant knowledge that a relapse could occur at any time, potentially worsening MS symptoms and existing function, create a state of chronic hypervigilance and worry. This pervasive sense of a loss of control over one’s own body and life is a catalyst for anxiety. Anxiety creates a vicious, self-perpetuating cycle where the physical and psychiatric symptoms mutually reinforce one another.

Anxiety cycle

Multiple stressors

Beyond this overarching uncertainty, living with MS entails a host of stressors.

  • Diagnosis. The diagnostic journey is a period of intense anxiety, often involving a prolonged period of uncertainty as symptoms are investigated. Once diagnosed, patients face a continuous process of adjusting and readjusting to changing abilities.
  • Hidden problems. The invisibility of some of the most burdensome symptoms, such as debilitating fatigue, cognitive fog, or sensory disturbances, can lead to a profound sense of feeling misunderstood, isolated and frustrated.
  • Visible symptoms. Conversely, the emergence of visible symptoms, like a limp or the need for a mobility aid, can bring its own anxieties related to stigma and self-image.
  • Daily life. Financial concerns related to healthcare costs, employment and the ability to continue working, as well as the impact of MS on relationships and potential parenting, may further increase anxiety. 

Existential threat

Profound existential and symbolic threats to a person’s sense of self can further exacerbate anxiety. The sense of loss triggered by a diagnosis of MS – loss of a healthy body, a previously held future and a former identity – is followed by changes in fundamental life roles. This can lead to feelings of inadequacy, guilt and a crisis of identity – perceived as a threat to one’s core self. The constant need to adapt to new limitations can feel like a continuous erosion of the self, and the fear of future disability becomes a fear of further loss of identity.

Addressing this existential dimension of anxiety is crucial for promoting long-term psychological adjustment and overall well-being. Treatment often involves helping individuals grieve their losses, redefine their sense of self and purpose within the context of their illness, and find new sources of meaning and value in their lives. 

Cognitive impairment

The impact of anxiety on cognitive function is well documented. Cognitive impairment, particularly slowed information processing speed, is a common and debilitating feature of MS. Anxiety has a detrimental effect on cognitive domains that are already compromised, such as attention and executive functions. It does this by increasing an individual’s awareness of task-irrelevant, often threat-related, stimuli, which interferes with the goal-oriented cognitive processing required for the task at hand. Thus, the underlying cognitive deficit from MS is compounded by the cognitive interference from anxiety, leading to a greater overall level of impairment than either condition would cause alone. Importantly, therefore, treating a patient’s anxiety can lead to measurable improvements in their cognitive functioning. 

Mood, fatigue, pain and sleep – a vicious cycle

Emotional problems rarely occur in isolation in MS; they are typically part of a clinical syndrome including fatigue, pain and poor sleep. This interconnected symptom cluster reduces health-related quality of life and establishes significant barriers to therapy and lifestyle modification.

Fatigue

Fatigue is one of the most common and disabling symptoms of MS, and it is strongly and consistently correlated with anxiety. This is not a simple correlation but a predictive relationship. Higher levels of anxiety at one point in time can predict the severity of fatigue at a later date. Conversely, higher levels of fatigue can predict the later development or worsening of anxiety.

The severity of depression in highly fatigued people with MS also makes the management of fatigue a high priority in reducing the overall psychiatric burden and allowing patients to engage in psychological interventions such as cognitive behavioural therapy (CBT).

Pain and emotional distress

A two-way relationship also exists between pain and anxiety, where anxiety is associated with higher reported pain intensity and greater interference of pain with daily activities.  The pain symptoms cause distress and anxiety, and the physical and mental state of anxiety (e.g. muscle tension, worry, poor sleep) in turn exacerbates the symptoms. Moderate or severe intensity pain that interferes with work, household activities or enjoyment of life affects about one-third of people with MS.

Sleep

Sleep is probably the most neglected MS-related problem in routine clinical practice; most people with MS have a sleep disorder. Depression, anxiety, pain and many other MS-related symptoms affect sleep quality. Therefore, it is challenging to manage MS-related emotional disorders without addressing sleep quality.

Lifestyle management and adherence

The cyclical nature of this grouping of mood disorder, fatigue, pain and poor sleep creates barriers to effective management. Emotional distress and physical symptoms can hamper efforts to start or maintain a healthy lifestyle. Since modifiable lifestyle factors (e.g. exercise) are associated with reduced pain burden, a vicious cycle is established: the disease causes emotional distress, the emotional distress prevents adherence to healthy behaviours, and the lack of healthy behaviours exacerbates physical symptoms.

Inappropriate laughing and crying

Inappropriate laughing and crying (pseudobulbar affect, PBA) are two neglected symptoms that often go undetected and untreated in people with MS. This doesn’t have to be the case. They are a further sign of significant damage to the brain and yet another reason to diagnose and treat MS early and effectively.

Case study 

When I first met her, she was in her early fifties. She had had MS for over 20 years. Her family now kept her at home, isolated from the wider world. Her behaviour would embarrass them. Why?

She suffered from pathological laughter and occasionally inappropriate crying; her husband and children could not deal with this in public. She was clearly very disabled when I met her; she was unsteady on her feet and had slurred speech and dancing eyes from cerebellar problems. She had gross cognitive impairment. When I introduced myself to her, she burst into tears. Within 2−3 months of starting sertraline, a selective serotonin reuptake inhibitor (SSRI), her husband informed me that her laughing and crying episodes had improved by over 50% and the family were now taking her out regularly. He was very grateful that I had been able to educate them about her symptoms and, more importantly, help her and them as a family deal with this problem.

PBA is diagnosed using standardised scales or questionnaires, which can be self-administered (Center for Neurologic Study-Lability Scale [CNS-LS]). These symptoms respond to tricyclic and SSRI antidepressants and to a combination pill (Nuedexta®; licensed in the USA) that includes dextromethorphan hydrobromide and quinidine sulfate. 

Management of emotional disorders                                                     

Routine screening, targeted drug treatment and structured psychological and behavioural therapies are core components of integrated care in MS. Emotional changes in MS require treatment, just as physical symptoms do.

Screening and education

Routine screening for both anxiety and depression should be part of standard MS care and should be conducted at all scheduled neurological visits. You may be asked to complete different screening questionnaires for depression, anxiety, fatigue and poor sleep. Ideally these should be done before your appointment so that the healthcare professional (HCP) can act on them during the consultation. 

HCPs should educate their patients and their families about potential emotional changes associated with MS, in particular, irritability, crying and mood swings. This education should help reduce the stigma and embarrassment associated with emotional outbursts and enable the patient’s support network to develop coping strategies.

Drug treatment

Drug treatment must be tailored to the specific diagnosis and emotional disorder.

  • Depression and anxiety: The standard use of selective serotonin reuptake inhibitors (SSRIs) and serotonin−norepinephrine reuptake inhibitors (SNRIs) is recommended for the management of clinical depression and anxiety disorders.
  • Irritability: Treatment options for irritability include SSRI antidepressants, which are often needed in addition to CBT. 
  • Pseudobulbar affect (PBA): Low-dose tricyclic or SSRI antidepressants can be effective in the treatment of PBA, but their use is off-label. In the USA, the combination of dextromethorphan hydrobromide and quinidine sulfate has been approved for PBA. In other countries, the combination of these two drugs can be effective in PBA, but again, the use of these two drugs separately is off-label and not recommended.
  • Apathy: Therapeutic strategies, such as cognitive rehabilitation, that enhance cognitive processing speed and executive function are more appropriate for apathy than antidepressants. However, such approaches are hard to access on the UK NHS and are not available in many healthcare systems. There are no licensed medications for apathy, but anecdotal evidence suggests that fampridine and some stimulants may help.
  • Further research: Properly randomised controlled trials are needed to determine the effectiveness of drugs that some patients obtain and use without a prescription. These include cannabis, psychedelics and ketamine, which are currently not licensed for managing anxiety in MS and are not advised.

Psychological and behavioural interventions

Evidence-based structured psychological interventions are as important as drug treatment for the management of anxiety and depression and should be considered a first-line approach in MS. CBT can address maladaptive thought patterns (e.g. catastrophic thinking about the future) and avoidant behaviours common in anxiety. Acceptance and commitment therapy (ACT) focuses on promoting psychological flexibility and acceptance, which is crucial for managing the reactive distress, grief and fear stemming from the unpredictable nature of the disease. Mindfulness, relaxation techniques and structured exercise programs have also been shown to manage anxiety and stress effectively. 

Interventions such as physical activity and social therapies enable some people with MS to process the grief and losses imposed by MS. Simple behavioural strategies, such as taking a break from a conversation when emotions escalate, can also be beneficial. 

Protective factors

Several protective factors can bolster resilience and lower the risk of anxiety. Motivational coping styles that involve direct problem-solving and active participation in treatment planning (i.e. self-management) are associated with better adjustment. One of the most critical protective factors is the presence of social support. Robust practical and emotional help from friends and family, and the knowledge that help is available if needed, significantly reduces the risk of mood symptoms. Finding ways to continue participating in previously enjoyed activities, albeit with new limitations, are key to coping. Interventions aimed at strengthening coping skills, fostering optimism and building social support networks can play a crucial role in preventing and treating anxiety in this population.

The therapeutic challenge

There is substantial symptom overlap between anxiety and depression (e.g. sleep disturbance, fatigue, difficulty concentrating) and between these mood disorders and the primary symptoms of MS. This can make it challenging for HCPs to discern whether a specific symptom, e.g. fatigue, is primarily a neurological symptom of MS, a physical symptom of depression, a consequence of the hyperarousal and poor sleep of anxiety, or a combination of all three. Use of appropriate screening tools can help to ensure that both anxiety and depression are accurately identified and appropriately treated.

Conclusion

MS profoundly affects emotional health across a broad and complex spectrum, manifesting as major depressive disorders, high levels of anxiety, the neurological syndrome of pseudobulbar affect, the cognitive−behavioural syndrome of apathy and, rarely, mania. These emotional changes are driven by primary damage to cortical-subcortical and brainstem circuits, coupled with reactive psychological distress resulting from living with a chronic, unpredictable illness. The current standard of care mandates routine screening, targeted drug treatments and psychological support utilising CBT and ACT. 

Clinical decisions, Cognition and mental health

Medical gaslighting – what is it, and how to avoid it?

Doctors have a long history of ignoring patients’ symptoms and complaints. In MS, this phenomenon tends to affect the so-called ‘hidden’ symptoms and related problems that are difficult to treat. 

Key points

  • Medical ‘gaslighting’, where healthcare professionals (HCPs) dismiss or downplay a patient’s symptoms, is an issue that patients and HCPs should be aware of. It affects women more than men.
  • Safety-netting is a legitimate strategy whereby the HCP and the patient adopt a wait-and-see approach to avoid over-investigation and overdiagnosis. It is part of a shared decision-making process and should not be interpreted as gaslighting.
  • Medical gaslighting can be subtle, but useful strategies exist for detecting and avoiding it.
  • If you are being gaslighted, despite efforts to push back, don’t be afraid to make your healthcare system aware of the problem rather than suffer in silence.

A case scenario

Whenever I see my neurologist, he seems to fob me off as if I don’t have a problem. He disagrees with me when I tell him that my MS is getting worse. He tells me I am not getting worse as my MRI is stable and my neuro exam is unchanged. He doesn’t believe me when I tell him that I am becoming more forgetful and that my fatigue is affecting the quality of my work.  

Origin of the term ‘gaslighting’

The volume of medicolegal case studies where doctors have ignored patients’ symptoms and complaints illustrates the extent of a problem that is now being referred to as medical gaslighting. Medical gaslighting may occur if:

  • your symptoms or concerns are dismissed of ignored without cause
  • your symptoms are dismissed as being normal, without explanation
  • you are made to feel your healthcare provider is blaming you.

The term ‘gaslighting’ comes from the 1944 film Gaslight starring Ingrid Bergman. The movie tells of a man who manipulates his wife to such an extent that she begins to doubt her own sanity. Since then, the term gaslighting has been used to describe emotional abuse that makes someone question their version of reality. People are beginning to share their personal experiences of medical gaslighting on social media with the hashtag #medicalgaslighting. 

Prevalence and severity of medical gaslighting

An article in the British Medical Journal (BMJ) suggests women are more likely than men to suffer from medical gaslighting, particularly with ‘health problems such as endometriosis, fibromyalgia, and irritable bowel syndrome’.1 Worryingly, the article states: ‘when compared with men, women face longer waits to be given a diagnosis of cancer or heart disease’. The article goes on to imply that medical gaslighting is becoming more common and the term has been ‘used widely in connection with long COVID, particularly early on in the pandemic’, when some patients who were still experiencing symptoms months after infection with SARS-CoV-2 thought they were not treated seriously or investigated fully.

A short online survey I did among MS-Selfie readers in 2022 revealed that 88% of 423 responders reported being gaslighted.

Responses to the survey question, ‘Have you ever experienced medical gaslighting in relation to your MS?’ (based on results from 423 MS-Selfie readers).

I am probably guilty of medical gaslighting too; in some cases, this may be deliberate. Many patients come to me with pages of problems, and I simply don’t have the time to deal with all of them. Time, or more correctly, lack of time is therefore one reason for medical gaslighting. Another is lack of knowledge or experience and not being able to admit you don’t know. However, the most worrying reason is the power dynamic, with HCPs wanting to be in control or remain in control. 

MS-Selfie as an initiative tries to address this power dynamic by giving you useful information to self-manage your MS – or at least to ask the right questions. 

Safety-netting

I suspect safety-netting may be misinterpreted as gaslighting. Safety-netting describes activities both within the HCP consultation and at healthcare systems levels (diagnostic and treatment algorithms) to avoid over-investigation and overdiagnosis. Many symptoms are non-specific and because of uncertainty the HCP and the patient adopt a wait-and-see approach. The patient is given clear instructions on how to identify the need to seek further medical help if their condition fails to improve, changes, or if they have ongoing concerns about the problem. Safety-netting is considered good clinical practice. A recent BMJ article2 on safety-netting makes the following points:

  • Aggressively treating or investigating all patients with early undifferentiated illness is poor medical practice and can be harmful.
  • Time is an important diagnostic tool but creates a period of uncertainty and risk for patients with serious underlying conditions.
  • Safety-netting can help mitigate this risk, and a traffic light framework provides a structure for delivering safety-netting advice.

The point about safety-netting is that it needs to be done as a part of a shared-decision making process and it should therefore not be interpreted as gaslighting. 

How to identify and tackle medical gaslighting

A New York Times article on medical gaslighting warns that it can be subtle, and lists some red flags to watch for.3 

  1. Your HCP continually interrupts you, doesn’t allow you to elaborate and doesn’t appear to be an engaged listener.
  2. Your HCP minimises or downplays your symptoms, for example questioning whether you have pain.
  3. Your HCP refuses to discuss your symptoms.
  4. Your HCP will not order key investigations to rule out or confirm a diagnosis.
  5. You feel that your HCP is being rude, condescending or belittling. Your symptoms are blamed on a mental problem, but you are not provided with a mental health referral or screened for such a problem.

Now that we have recognised medical gaslighting as a significant problem in MS, please don’t allow a neurologist to gaslight you. The New York Times article suggests practical steps you can take to prevent this. 

  • Keep detailed notes and records. Patient-held notes transform consultations and force you to become a partner in your healthcare.
  • 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 are still being ignored, here are some of your options.

Get a second opinion and ask to switch to a new HCP
Look to support groups or forums. Many MS charities have helplines where you can discuss these issues
Appeal to a higher authority, the person above your HCP (their line manager). In the NHS, we have a straightforward procedure for patients to complain or question their care. It is called PALS (Patient Advice and Liaison Service)

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. 

Healthcare systems and the medical professions

We need to include medical gaslighting as part of the medical curriculum so that HCPs are made aware of it during their training. HCPs must buy into the model of patients being equal partners in the diagnosis and management of their disease. The paternalistic or older patronising model of healthcare where the HCP knows best is outmoded.

Gaslighting is another form of abuse or discriminatory behaviour, no different from sexism, racism or ageism. This raises the question, is it deliberate or an institutional problem, i.e. part of the dominant medical culture? I suspect the latter, and this is why it will need a wider campaign to tackle the problem, with clearly defined carrots (incentives/rewards) and sticks (disincentives/punishment) to change our behaviour. 

References

  1. Wise J. Sixty seconds on . . . medical gaslighting. BMJ 2022;378:o1974.
  2. Edwards PJ et al. Safety-netting in the consultation. BMJ 2022;378:e069094.
  3. Caron C. Feeling dismissed? How to spot ‘medical gaslighting’ and what to do about it. New York Times, 29 July 2022.
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. 

DMTs, Treatment strategy

Am I eligible for an MS disease-modifying therapy?

Key points

Do you know the eligibility criteria for MS disease-modifying therapies? And who decides what drugs can be prescribed for your MS?

  • Disease-modifying treatments (DMTs) change the long-term trajectory of MS and protect the central nervous system from further damage.
  • Regulators such as the European Medicines Agency (EMA) and the Federal Drug Administration (FDA) decide in which group(s) of patients a particular drug can be used, based on the results of clinical trials.
  • Once a drug has been licensed in your region, local payers decide whether to make it available within your country, based on cost-effective assessments.
  • If you have active MS, your level of disease activity, its severity and speed of development will determine which DMTs you can be offered.
  • In some countries, ocrelizumab has been approved for the treatment of active primary progressive MS (PPMS) and siponimod has been approved for the treatment of active secondary progressive MS.
  • Protecting upper limb function has been a neglected area; studies are now ongoing, however, with a view to finding DMTs that limit the progression of upper limb disability.

What do disease-modifying drugs do?

Disease-modifying therapies (DMTs) are treatments that change the natural history – that is, the long-term trajectory – of the disease. They reduce the rate of disability worsening and so protect the end-organ (in the case of MS, this is the central nervous system). To simplify, let’s say that a person with MS on no treatment may manage for an average of 18-20 years before needing to use a walking stick (corresponding to Expanded Disability Status Scale [EDSS] 6.0), while someone on treatment might manage without aid for 24 years, i.e. a 4-6-year delay, then the treatment can be called disease-modifying. (Please note, the treatment effect or 4-6-year delay in reaching EDSS 6.0 is an average and some people with MS will do better than others. Conversely, some will do worse than average.) 

Is interferon a DMT?

In the early days of interferon therapy, there was debate about whether simply reducing the relapse rate by 30% relative to placebo treatment, without slowing down the worsening of the disease over 2 years, was disease-modification. However, subsequent trials and follow-up of people with MS treated with interferon-beta showed a slowing down of disease worsening, delays in developing secondary progressive MS and a favourable impact on survival.1 

Do symptomatic treatments modify the disease?

Symptomatic treatments improve the symptoms associated with MS without affecting the natural history. Treatments are classified as symptomatic in relation to their mode of action; but some classes of treatment may yet prove to be disease-modifying. For example, we often use sodium channel blocking agents, such as phenytoin, carbamazepine, oxcarbazepine and lamotrigine, for MS-related neuralgia and other pain syndromes. However, there is evidence that this class of therapy may be neuroprotective and hence disease-modifying. 

Who decides on eligibility for a licensed DMT?

Regulators decide in which group of people with MS the DMT can be used, and they grant a licence for its use. Regulators include the EMA, the FDA and the Medicines and Healthcare products Regulatory Agency (MHRA in the UK).

Payers hold the purse strings and decide which licensed drugs to make available. They makecost-effectiveness assessments to try and optimise the use of the drug in clinical practice. Payers include medical insurance companies and the NHS in the UK. 

Guidelines are formulated to help healthcare professionals use DMTs in the most appropriate way within a particular healthcare system. Guidelines often go much further than the regulators and payers, in that they try to address potential ambiguities in the prescribing of DMTs. National, regional or local guidelines that provide expert clinical guidance include the UK NICE (National Institute for Health and Care Excellence) MS management guidelines and the Association of British Neurologists guidelines. 

In the NHS in England, we must abide by NHS England’s algorithm that is predominantly based on NICE technology appraisals, NICE standards of care and the Association of British Neurologists guidelines. To navigate the specifics of the eligibility criteria is quite complex. However, a simpler way of looking at this is to start by defining how active your MS is. 

How does disease activity affect my treatment options?

To be eligible for DMTs, you must have active MS. A summary of the four categories of disease activity is given below. Further details can be found in the section entitled Do I have active MS?

  1. Inactive MS – you are not currently eligible for DMTs.
  2. Active MS – you should be eligible for a so-called platform therapy (interferon-beta, glatiramer acetate, teriflunomide, dimethyl fumarate or ponesimod) and ocrelizumab or ofatumumab.
  3. Highly active MS – you are eligible for all therapies except natalizumab. Please note in England fingolimod can only be used as a second-line therapy (after another DMT has failed).
  4. Rapidly evolving severe MS – you should be eligible for all DMTs.

Advanced or progressive MS

Ocrelizumab and siponimod are now approved in several countries for the treatment of active PPMS and active SPMS, respectively. A classification of active PPMS requires recent MRI evidence of disease activity, that is, the formation of new T2 lesions and/or the presence of gadolinium-enhancing lesions in the last 3 years. Active SPMS is confirmed by the occurrence of superimposed relapses and/or the presence of new T2 lesions and/or gadolinium-enhancing lesions in the last 2 years. Based on these very narrow definitions, most patients with PPMS and SPMS will not be eligible for ocrelizumab or siponimod, respectively. The differences between the MRI criteria for active PPMS and active SPMS reflect the reality that people with PPMS are less likely to be having regular monitoring MRI scans.

Stages of MS currently not eligible for treatment

In the UK, people with MS who are wheelchair users are not eligible for DMTs. The reason for this is that patients with more advanced MS have generally been excluded from phase 3 clinical trials; hence there are no data to show whether licensed DMTs are effective in this group.

There is a long-held view that inflammation is reduced or absent in advanced MS. However, clinical, imaging and pathological data show that inflammation still plays a large, and possibly a major, role in advanced MS. Therefore, not targeting more advanced MS with an anti-inflammatory is counterintuitive.

The importance of upper limb function

In 2016, the #ThinkHand campaign was launched to raise awareness of the importance of hand and arm function in people with MS and the need for clinical trials in this population. Studies currently ongoing that focus on limiting upper limb disability progression include ChariotMS (oral cladribine)2 in people with advanced MS (UK only) and the global, multicentre O’HAND trial  (ocrelizumab)3 in participants with PPMS. 

Once someone with MS becomes a wheelchair user, they still have neuronal systems that are potentially modifiable – for example, upper limb, bulbar (speech and swallowing), cognition and visual function. There is an extensive evidence base showing that several licensed DMTs can slow the worsening of upper limb function despite subjects having advanced MS. Now that ocrelizumab and siponimod have been licensed for active primary and secondary progressive MS, respectively, these DMTs may form the platform for future add-on trials. 

References

  1. Goodin DS, et al. Survival in MS: a randomized cohort study 21 years after the start of the pivotal IFNβ-1b trial. Neurology 2012;78:1315 ̶ 22.
  2. National Institute for Health and Care Research (NIHR). MS clinical trial to focus on people who can’t walk. November 2020. Available at https://www.nihr.ac.uk/news/ms-clinical-trial-to-focus-on-people-who-cant-walk/26227 (accessed June 2022).
  3. US National Library of Medicine. A Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis (O’HAND). First posted July 2019. Available at https://clinicaltrials.gov/ct2/show/NCT04035005 (accessed June 2022).
Brain health and holistic management of MS, Treatment strategy

What are the consequences of not treating MS?

Are there valid reasons not to treat MS with a disease-modifying therapy? What are the consequences of not treating MS? Is watchful waiting justified?

Key points

  • Untreated MS will, given time, result in physical disability, impaired quality of life and ‘hidden’ problems such as cognitive impairment, anxiety and depression.
  • Brain atrophy, or shrinkage, occurs at a faster rate in people with MS than in healthy individuals.
  • Optic neuritis, inflammation or destruction of nerve fibres in the brain and spinal cord, and extensive damage to the cerebral cortex (grey matter) are some consequences of MS lesion development.
  • Quality of life impacts may include reduced mobility, relationship difficulties, increased likelihood of unemployment and memory impairment.
  • Without treatment, the life expectancy of people with MS is reduced by about 6 ̶ 8 years.
  • There are, however, several valid reasons why some people with MS prefer not to receive disease-modifying treatments.

Risks from no disease-modifying treatment

Many patients ask me what will happen to their MS if they don’t take a disease-modifying treatment (DMT) and how effective DMTs are at preventing negative outcomes. Here I try and address questions you need to ask yourself before starting a DMT.

If you are an individual with MS, predicting your disease course is difficult. However, many studies monitoring groups of people with MS show patterns in relation to the progression of the disease and its outcome, with various data sets being consistent.

Given sufficient time, most people with MS who are not treated will become disabled. Most people focus on physical disability, but MS causes many hidden problems, such as cognitive impairment, anxiety and depression.

How untreated MS can progress – headline results

The slides below summarise some of the outcomes of untreated MS; these include brain changes (atrophy), further MS lesion development, reduced health-related quality of life, long-term impact on physical and mental health and shorter life expectancy. (To enlarge an individual slide, click on the arrow at the top right.)

Brain changes
MS lesion development
Quality of life impact
Long-term outlook

DMTs have changed the landscape

It is important to note that these outcomes are from the pre-DMT era and don’t apply to populations of people with MS treated with DMTs. New real-life data indicate that DMTs, particularly high-efficacy DMTs, are preventing many of these problems. By not being on a DMT, if you have active MS, you are at risk of acquiring damage from focal inflammatory lesions. Early in the disease course, you may not be aware of this damage because of the remarkable capacity of the nervous system to compensate for damage (neurological reserve). However, once the compensatory mechanisms have been exhausted, further damage results in overt disability. It is important to regard DMTs as preventive treatments, i.e. their aim is to delay, and hopefully prevent, future disability.

Possible reasons for not receiving a DMT

Many people with MS will not be on a DMT, for a variety of reasons. The list below is probably not extensive; if you know of other reasons why someone who qualifies is not taking a DMT, please let me know.

Inactive MS

Someone with inactive MS will not be eligible for a DMT. There is no standard definition of active MS. To me, active MS is recent evidence of focal inflammatory disease activity, defined as:

  • clinical relapse(s) in the last 2 years
  • OR magnetic resonance imaging (MRI) activity in the last 12 ̶ 36 months (new or enlarging T2 lesions or T1 Gd-enhancing lesions)
  • OR a raised cerebrospinal fluid (CSF) neurofilament light chain level in the last 12 months.

Worsening disability in MS without focal inflammatory disease activity is not active disease. It can be due to damage caused by past inflammation, smouldering MS or the effects of premature ageing; anti-inflammatory DMTs can’t address this problem. We need different types of DMTs to address these mechanisms – for example, neuroprotective and/or remyelination therapies and anti-ageing therapies.

Watchful waiting

In many situations, some neurologists think someone with MS will end up having benign disease, so they are not prepared to start treatment until the patient develops some overt disability. I abhor this practice and it is one of the reasons I spend so much of my time disseminating knowledge and getting involved with health politics. Watchful waiting, in terms of treating MS, is not supported by data. The earlier and more effectively you treat MS, the better the outcome. The only situation I could condone watchful waiting in someone with active MS is when the diagnosis of MS is in question. Sometimes in neurology, time is the best diagnostician. If the person has MS, it will declare itself with further disease activity, and this would be the trigger to start a DMT.

Family planning

Trying to fall pregnant, pregnancy or breastfeeding are common reasons to interrupt or stop DMTs. Please note that most neurologists now have options to treat MS during pregnancy and while breastfeeding, so this is becoming a less common reason for not taking a DMT.

Risk aversion

Some people with MS are not prepared to take the potential risks associated with DMTs.

Personal reasons

Some people with MS don’t believe in having their MS treated, preferring to try alternative medicines and turn down traditional DMTs. If you are one of these people, I would recommend you continue to interact with your MS team and have regular monitoring of your MS (clinical, MRI, patient-related outcome measures [PROMS] and possibly CSF analyses). Then, if these alternative strategies don’t work, you will keep open the option of treatment with a ‘traditional DMT‘. Most alternative treatment strategies for MS are compatible with DMTs and hence should be viewed as complementary. Understanding the difference between complementary and alternative treatments is important. Complementary treatment strategies are part of the holistic management of MS.

Financial constraints

In some parts of the world, MS treatment is not covered by a national health service or medical insurance scheme and some people with MS simply can’t afford DMTs. Even in rich countries, people with MS who are disenfranchised don’t have access to treatment; these may include illegal immigrants, refugees and asylum seekers waiting for their applications to be processed.

Progressive or more advanced MS

In most countries, neurologists don’t initiate treatment in patients with more advanced MS. This approach is based on a lack of evidence of the effectiveness of DMTs in this population. However, we are increasingly offering ocrelizumab (for active primary progressive MS), siponimod (for active secondary progressive MS) or off-label therapies on a compassionate basis to people with more advanced MS. In addition, there is also the potential to participate in clinical trials of new treatments for more advanced MS.

Ageism

Some healthcare systems and some neurologists are reluctant to start DMTs in people with MS who are over a certain age. This is based on a lack of evidence of the effectiveness of DMTs in this population, and it is why we need to do clinical trials in older people with MS.

Comorbidities

Many people have other medical problems for which the treatment takes priority over the treatment of MS. For example, a patient of mine was diagnosed with stage four bowel cancer. After her surgery, she started an intensive period of chemotherapy during which we stopped her DMT.

References

  1. Fisher E, et al. Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol 2008;64:255–65.
  2. Barkhof F, et al. Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol 2009;5:256–66.
  3. Simon JH. Brain atrophy in multiple sclerosis: what we know and would like to know. Mult Scler 2006;12:679–87.
  4. Ziemssen T, et al. Optimizing treatment success in multiple sclerosis. J Neurol 2016;263:1053–65.
  5. Hickman SJ, et al. Detection of optic nerve atrophy following a single episode of unilateral optic neuritis by MRI using a fat-saturated short-echo fast FLAIR sequence. Neuroradiology 2001;43:123–8.
  6. Trapp BD, et al. Axonal transection in the lesions of multiple sclerosis. N Engl J Med 1998;338:278–85.
  7. Peterson JW, et al. Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 2001;50:389–400.
  8. Orme M, et al. The effect of disease, functional status, and relapses on the utility of people with multiple sclerosis in the UK. Value Health 2007;10:54–60.
  9. Pfleger CC, et al. Social consequences of multiple sclerosis (1): early pension and temporary unemployment – a historical prospective cohort study. Mult Scler 2010;16:121–6.
  10. Kobelt G, et al. Costs and quality of life of patients with multiple sclerosis in Europe. J Neurol Neurosurg Psychiatry 2006;77:918–26.
  11. Feuillet L, et al. Early cognitive impairment in patients with clinically isolated syndrome suggestive of multiple sclerosis. Mult Scler 2007;13:124–7. 
  12. Confavreux C and Compston A. Chapter 4. The natural history of multiple sclerosis. In: McAlpine’s Multiple Sclerosis, Fourth Edition, 2006; 183 ̶ 272. Churchill Livingstone.
  13. Weinshenker BG et al. The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability. Brain 1989;112:133 ̶ 46.
  14. Torkildsen GN, et al. Survival and cause of death in multiple sclerosis: results from a 50-year follow-up in Western Norway. Mult Scler 2008;14:1191–8.
  15. Kingwell E, et al. Relative mortality and survival in multiple sclerosis: findings from British Columbia, Canada. J Neurol Neurosurg Psychiatry 2012;83:61–6.
  16. Sadovnick AD, et al. Cause of death in patients attending multiple sclerosis clinics. Neurology 1991;41:1193–6.
  17. Brenner P, et al. Multiple sclerosis and risk of attempted and completed suicide – a cohort study. Eur J Neurol 2016;23:1329–36. 

Diagnosis, Stages of MS

Do I have active MS?

Before deciding to start a disease-modifying therapy you need to know if you have active MS.

Key points

  • To qualify for a disease-modifying treatment for MS you must have active disease.
  • Active MS is characterised by relapses (new symptomatic or asymptomatic lesions); the clinical diagnosis of relapse may be supported by MRI or CSF evidence of activity.
  • Different levels of disease activity qualify for different types of DMT.
  • Diagnostic criteria for MS have evolved considerably over the past two decades; this has helped to make treatment decisions earlier and easier, both for MS neurologists and for people with MS.

To be eligible for disease-modifying therapy (DMT) you must have ‘active MS’. This term is increasingly used to refer to current or recent evidence of focal inflammatory activity, i.e. new lesions on magnetic resonance imaging (MRI) or a relapse. Inflammation damages axons, or nerve processes. When a lesion develops, the effects of inflammatory mediators can cut (transect) axons, demyelinate them or stop them from working.

By contrast, the gradual worsening of disability that occurs in people with more advanced MS (which may, or may not, occur in the presence of focal inflammatory activity) has many potential causes, only one of which is focal inflammation.

Signs of active MS

Relapses

When a new MS lesion occurs in an eloquent part of the central nervous system it causes new symptoms or exacerbates old ones – this is usually interpreted as a relapse. Relapses, by definition, last at least 24 hours in the absence of infection or fever.

Criteria for ‘active’ MS accepted by many MS health professionals. CSF, cerebrospinal fluid; NFL, neurofilament light.
*Some neurologists accept 24 months, 36 months or even more when assessing MRI activity. There is no international consensus on the gap between the baseline and new MRI scan to define active disease.

Asymptomatic lesions

Most focal MS disease activity does not cause any overt symptoms because the brain has a way of compensating for damage. For every clinical relapse, there are at least 10 or more lesions on MRI. Therefore, what we see clinically in terms of relapses is the tip of the iceberg. Even standard MRI is relatively insensitive in detecting and monitoring MS disease activity; it misses new lesions that are smaller than 3 ̶ 4 mm in size and does not detect most lesions that occur in the grey matter of the brain (cortex and deep grey matter nuclei, e.g. thalamus and basal ganglia). Therefore, MRI scans also reveal just the tip of the iceberg. This is one of the reasons we also use cerebrospinal fluid (CSF) neurofilament levels as a marker of this microscopic activity.

Disease activity levels

Inactive MS

Many people with MS experience frequent intermittent symptoms or ‘pseudorelapses’ that come on when they are tired, after exercise or have a raised body temperature from a fever, exercise, hot bath or a warm environment. These intermittent symptoms are usually quite stereotyped and last minutes to hours. They are indicative of a previously damaged pathway but do not represent a relapse or disease activity.

Active MS

Most neurologists require evidence of disease activity in the last 12 months, with some of us accepting a 24-month or 36-month window if there is no serial or regular MRI support. However, if you have had no relapses or MRI evidence of new lesions in the last 24 months, then your MS is defined as inactive. (This does not mean your MS is necessarily stable; you could have worsening disability as part of the progressive or smouldering phase of the disease.) Inactive MS needs to be monitored in case it reactivates, in which case you could become eligible for treatment.

Inactive MS - format updated 180625 SS

Schematic showing different levels of MS disease activity.
*Some neurologists accept MRI activity in the last 24 months, 36 months or even longer as a criterion for active MS.

Highly active MS and rapidly evolving severe MS

Active MS has been divided into an additional two categories that have implications for DMT prescribing (depending on where you live).

  • Highly active MS describes MS with unchanged or increased relapse rates, or ongoing severe relapses compared with the previous year, despite treatment with beta-interferon or another so-called first-line therapy. In England, patients in this subgroup are eligible for natalizumab, alemtuzumab, fingolimod and cladribine.
  • Rapidly evolving severe MS (RES) is defined as two disabling relapses and MRI evidence of activity within a 12-month period. In England, patients in this subgroup are eligible for natalizumab, alemtuzumab and cladribine.

Evolution of diagnostic criteria

In the early 2000s, disease activity was defined using clinical criteria only; you needed at least two documented relapses in the last 2 years to be eligible for DMT.1 This meant that a neurologist had to examine you to confirm abnormalities compatible with a relapse. However, many people with MS without rapid access to a neurologist would recover before being assessed, meaning that their relapses often could not be documented. This was very frustrating for someone wanting to start a DMT. If patients had MRI evidence to support recent disease activity, how could we deny them access to a DMT because they were not seen in a timely way to have their relapse documented in the clinical notes?

In 2009, the criteria for diagnosing MS incorporated MRI into the definition to allow us to treat so-called high-risk patients with CIS (clinically isolated syndromes compatible with demyelination). These criteria required patients with CIS to have nine or more T2 lesions on MRI or at least one gadolinium-enhancing lesion. These MRI criteria were based on the McDonald diagnostic criteria at the time.2 These eligibility criteria evolved further in 2014, once alemtuzumab was licensed, to include clinical or MRI activity.

References

  1. 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.
  2. Polman CH, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011;69:292–302.
Brain health and holistic management of MS, Causes and prevention of MS

What prognostic group do I fall into?

Having some idea of how bad your MS is, or not, will allow you to discuss important issues with your neurologist so that you can make an informed decision about your MS treatment.

Key points

  • It is hard to predict the disease course of MS accurately for an individual.
  • Population data allow us to define three broad prognostic MS categories: good, indeterminate or poor.
  • Given sufficient time, most people with MS will do badly without treatment.
  • Factors linked to poor prognosis in untreated people with MS are listed.
  • The wide use of disease-modifying therapies is changing the natural history of MS for the better.
  • Adopting a healthy lifestyle, in parallel with appropriate treatment, can help to improve outcomes.  

Predicting MS outcomes: an imperfect science

We can’t predict the prognosis of an individual person with MS very accurately. So don’t let your neurologist mislead you if he or she says you are likely to have benign MS. ‘Benign MS’ is a relative term and can only be used retrospectively once you have had MS for many years or decades. In the era before disease-modifying treatments (DMTs), most people with MS would eventually become disabled, which is why I prefer not to use the term benign MS to predict outcomes. I now use it as a treatment aim, because we want all people with MS to have benign disease.

Three broad prognostic categories

Applying population data to place an individual into a broad prognostic group is often helpful. It allows you to frame your disease in terms of potential outcomes and may help you balance the risks of some treatments against the potential impact of MS later in your life. Predicting outcomes in MS is comparable to an actuary working in the insurance industry; we try to give you an average prognosis with a wide range of possibilities or errors. For this reason, I try to keep it simple and classify people with MS into three prognostic categories: poor, indeterminate, or good. Poor in this context means that if you leave MS to its own devices and let it run its natural course, the average person in this category will do badly.

Most people with a predicted poor prognosis will do badly without treatment for their MS.

Given sufficient time, most people with MS will deteriorate without treatment. This is why I actively promote treatment based on the scientific rationale that preventing damage now will protect your brain reserve and cognitive reserve and improve your long-term outcome. This is the philosophy behind the MS Brain Health initiative and the report Brain health: time matters in multiple sclerosis,1 which everyone with MS should take time to read. 

Factors linked to poor prognosis

Below is a list of factors that have been linked to poor prognosis in people who have not received a DMT. If you have fewer than five of these factors, you are likely to have a good outcome. In comparison, people with ten or more of these factors fall into the poor prognostic group. Most people with MS fall into the intermediate (indeterminate) prognostic group, with 5–10 of these factors. Some of these baseline factors are modifiable,2,3 so you can make the effort to help improve your own prognosis. 

Please note that the factors listed here only apply to people with MS who are untreated.  It is clear that DMTs are changing the outcome of MS.

  1. Older age of onset (greater than 40 years).
  2. Male sex.
  3. Multifocal onset – more than one site in the nervous system involved with the initial attack.
  4. Efferent or effector system is affected early – that is, the motor (power), cerebellar (balance and coordination) or bladder and bowel functions.  
  5. Partial or no recovery from initial relapses – do you have residual deficits from your initial attacks?
  6. A high relapse rate in the first 2 years – that is, more than two relapses. 
  7. Early disability – an Expanded Disability Status Scale (EDSS) score > 3.0 within 5 years of symptom onset indicates a poor prognosis. You can calculate your EDSS using an online calculator (web-EDSS calculator).
  8. Abnormal magnetic resonance imaging (MRI) scan with large lesion load – more than nine T2 lesions (white blobs) on the baseline MRI.
  9. Active or enhancing lesions on your baseline (initial) MRI – enhancing lesions imply that the lesions are new and actively inflamed.
  10. Posterior fossa lesions on the MRI – these refer to lesions in the back of the brain that involve the brainstem and cerebellum.
  11. Lesions in the spinal cord on MRI.
  12. Obvious early brain atrophy on MRI – brain atrophy refers to premature shrinkage of the brain over and above what you would expect for your age. This information is unlikely to be available to you because neuroradiologists often do not measure or comment on it. 
  13. Retinal thinning on optic coherence tomography (OCT) – people with MS who have lost a lot of retinal nerve fibres do worse than people with a normal retina. Yes, the eye is truly a window into what is happening in the brain of someone with MS. 
  14. Abnormal cerebrospinal fluid – positive immunoglobulin (Ig) bands (known as oligoclonal bands, OCBs) in the spinal fluid.
  15. Raised neurofilament levels in your spinal fluid – this test may not be part of routine care at your neurology centre. Neurofilaments are proteins that are released from damaged nerve fibres, and high neurofilament levels indicate greater damage and poorer outcome than low levels.
  16. Low vitamin D levels – this is controversial, but several studies have shown that people with MS with low vitamin D levels do worse than those with higher levels. These observations do not necessarily imply that by taking vitamin D you will do better. Low vitamin D levels may be related to reverse causation, in that the MS-associated inflammation uses up vitamin D; more inflammation indicates worse MS and is therefore linked with greater depletion of vitamin D levels.
  17. Smoking – smokers with MS do worse than non-smokers. This is modifiable and it is one of many reasons why you should try and give up smoking. 
  18. Comorbidities – people with MS who are obese, have diabetes, prediabetes, hypertension or raised cholesterol do worse than people with MS without these comorbidities.4
  19. Cognitive impairment – people with MS with poor cognitive function do worse than people with MS with good cognition. You can’t really assess your own cognition at present; you need to have it tested by a neuropsychologist.

‘It won’t happen to me’

Humans have interesting psychology in that they tend to consider themselves to be the exception to the rule. Gamblers don’t enter a casino to lose; they always believe they will win. A person with lung cancer who starts chemotherapy believes they will be one of the 10% who is cured. When someone is diagnosed with MS, they believe they will be one of the 30% with benign disease. (The current view among MS neurologists is that 30% of untreated people with MS will have benign disease.) 

This definition of ‘benign MS’ is based on having no or little disability at 15 years since onset, i.e., an EDSS score of 3.0 or less (no visible disability). However, when you interrogate people with so-called benign MS you find that more than 50% of them have hidden symptoms of depression, anxiety or cognitive impairment. Can we really justify this definition of benign MS? What is more, when you follow people with benign MS past 15 years, only 15% remain benign at 25 years and 5% at 30 years. If you get to 40 years of follow-up, half of these with benign MS will become disabled over the next 10 years.

Moving towards a more favourable outcome

Many will state that these figures are now out of date and there are newer and better figures, which show MS is a more benign disease. You are right, and there are several very good reasons for this. In population-based studies, the proportion of subjects with benign MS is greater than in hospital- or clinic-based studies; for example, in the Olmsted Mayo Clinic MS population, about 45% have benign disease at 15 years. The reason for this is that people with MS with benign disease often drop out of hospital follow-up, but still show up in population-based studies. 

The earlier diagnosis of MS, that is, identification of those who would not have been diagnosed in the past, is changing the definition of MS. For example, most people with a clinically isolated syndrome (CIS) are now being diagnosed as having MS. The wide use of DMTs is beginning to change the natural history of MS for the better; making sure that people with MS adopt a healthy lifestyle is another strategy that can be done in parallel. 

With currently available high-efficacy DMTs and the prospect of effective combination treatments in the future, the proportion of people with MS who experience normal ageing is set to increase. The blue areas illustrate the likely number of people with MS in each prognostic category.
With currently available high-efficacy DMTs and the prospect of effective combination treatments in the future, the proportion of people with MS who experience normal ageing is set to increase. The blue areas illustrate the likely number of people with MS in each prognostic category.
With currently available high-efficacy DMTs and the prospect of effective combination treatments in the future, the proportion of people with MS who experience normal ageing is set to increase. The blue areas illustrate the likely number of people with MS in each prognostic category.
With currently available high-efficacy DMTs and the prospect of effective combination treatments in the future, the proportion of people with MS who experience normal ageing is set to increase. The blue areas illustrate the likely number of people with MS in each prognostic category.

With currently available high-efficacy DMTs and the prospect of effective combination treatments in the future, the proportion of people with MS who experience normal ageing is set to increase. The blue areas illustrate the likely proportion of people with MS in each prognostic category.

The above figures illustrate what we aim to do with currently available high-efficacy DMTs (compared with older, lower efficacy treatments). We are simply trying to move you to the right, into a more favourable prognostic group. In other words, we want to make sure your MS is benign and that you reach old age with as healthy a brain as possible. Your brain reserve and cognitive reserve protect you from developing age-related cognitive impairment and dementia. MS reduces both of these reserves, which is why it is so important to protect them. With the prospect of effective combination treatments in the future, the proportion of people with MS who experience normal ageing is set to increase.

References

  1. Giovannoni G, et al. Brain health: time matters in multiple sclerosis. 2015, Oxford Health Policy Forum CIC.
  2. Miller DH, et al. Clinically isolated syndromes. Lancet Neurol 2012: 11:157–69.
  3. Weld-Blundell IV, et al. Lifestyle and complementary therapies in multiple sclerosis guidelines: Systematic review. Acta Neurol Scand 2022;145:379–92.
  4. Kappus N, et al. Cardiovascular risk factors are associated with increased lesion burden and brain atrophy in multiple sclerosis. J Neurol Neurosurg Psychiatry 2016;87:181–7.
Stages of MS

What type of MS do I have?

MS has historically been classified into different subtypes, and this subdivision dictates what treatments you are eligible for. These MS disease subtypes are not supported biologically, however, and many MS neurologists are of the opinion that MS is one disease.1

Key points

  • The difference between relapsing MS and non-relapsing progressive MS is explained.
  • The stages of MS have different labels, for historical development and reimbursement reasons, but biologically MS is one disease.
  • From a treatment perspective, the key thing is to know if your MS is active or inactive.
  • Active MS can be differentiated from inactive MS by relapses, MRI evidence of disease activity and raised neurofilament levels in the cerebrospinal fluid.

Type of MS

You should be able to classify yourself as having either relapsing MS or non-relapsing progressive MS. Knowing what type of MS has been diagnosed and whether your MS is active or inactive will allow you to ask your MS neurologist questions about the MS treatments available to you. 

Around 85–90% of people with MS start with so-called relapse-onset MS, i.e. they have a definite attack of symptoms that is usually followed by a period of complete or incomplete recovery. A single attack may be labelled as a clinically isolated syndrome (CIS): it does not fulfil the current diagnostic criteria for full-blown MS, but it means someone is at risk of further attacks and hence of developing MS in the future.

EDSS, Expanded Disability Status Scale score
EDSS, Expanded Disability Status Scale score

Once you have more attacks, either clinically in the form of relapse or subclinically with new lesions on magnetic resonance imaging (MRI), then you are usually diagnosed as having MS. The diagram below illustrates the typical course of repeated relapses and remissions, with worsening disability over time, that characterises so-called relapsing–remitting MS (RRMS).

After a variable period, people with relapse-onset MS may notice worsening neurological function without improvement. This is called secondary progressive MS (SPMS) and it can occur with superimposed relapses (so-called relapsing SPMS [RSPMS]) or without relapses.

EDSS, Expanded Disability Status Scale score
EDSS, Expanded Disability Status Scale score

A small number of people with MS (10–15%) will present with worsening neurological function without a prior history of relapses; this is called primary progressive MS (PPMS).

Interestingly, some people with PPMS go on to have relapses, and this is referred to as progressive relapsing MS (PRMS).

EDSS, Expanded Disability Status Scale score
EDSS, Expanded Disability Status Scale score

Rarely, someone may present with worsening neurological function, similar to PPMS, but have a prior history of just one relapse. This is referred to as single-attack progressive MS (SAP), but most MS specialists classify these patients as having SPMS. 

In summary …

  • Relapsing MS captures all people with MS who are still having relapses, i.e. within the last 2 years, and includes RRMS, RSPMS and PRMS.
  • Non-relapsing progressive MS refers to SPMS and PPMS: these latter two groups should have no history of recent relapses, i.e. in the last 2 years.

To further confuse things, non-relapsing progressive MS used to be referred to as chronic progressive MS (see below). 

Why is this important?

Different DMTs are licensed for different types of MS, and many treatment guidelines specifically state the type of MS for which a particular drug can be used.

Is MS one or more diseases?

In the past, MS was regarded as one disease: either you had MS, or you did not. The stages were referred to as early relapsing MS or chronic progressive MS, but MS was still one disease. 

When disease-modifying therapies (DMTs) were developed, MS was split into multiple sub-types. This categorisation was driven by commercial considerations, and it allowed interferon-beta to be licensed in the US under the Orphan Drug Act. The classification of orphan disease in the US requires there to be fewer than 200,000 people with that diagnosis. Dividing MS into RRMS, SPMS, PPMS and later CIS ensured that each category met this criterion. 

Since then, PRMS and radiologically isolated syndrome (RIS) have been added as potential subtypes. These classifications tend to be arbitrary and overlap, but there is no biological basis to support MS being more than one disease. 

Is your MS active or inactive?

From a treatment perspective, it is important to know if your disease is active or inactive. In active MS, there is evidence of ongoing inflammation in the brain and spinal cord. If you are having relapses, are developing new lesions on MRI or have raised neurofilament (NFL) levels in your cerebrospinal fluid (CSF) or blood, your MS is active. 

Active MS responds to anti-inflammatory treatments; inactive MS is less responsive to currently licensed DMTs. 

Criteria for ‘active’ MS accepted by many MS health professionals. CSF, cerebrospinal fluid; NFL, neurofilament light.
*Some neurologists accept 24 months, 36 months or even longer when assessing MRI activity. There is no international consensus on the gap between the baseline and new MRI scan to define active disease.

The term progressive MS refers to the stage of MS when your disability gets worse – independent of relapses, and possibly of focal inflammatory lesions. I say ‘possibly’, because our current MRI scans don’t show new or enlarging microscopic lesions but only those that are larger than ~3–4 mm. NFL measurements in either the CSF or blood have the advantage of being additive and integrating inflammatory activity. In my experience, about one in ten patients classified as ‘inactive’ based on clinical and MRI activity is found to have active MS when CSF NFL levels are analysed. Unfortunately, however, many MS neurologists, regulators and payers do not accept this latest definition of MS disease activity because tests for NFL levels are currently not widely available. 

In conclusion, knowing the type of MS you have and whether your disease is active or inactive will allow you to discuss with your MS specialist the kinds of treatment available to you. 

References

Giovannoni G, et al. Smouldering multiple sclerosis: the ‘real MS’. Ther Adv Neurol Disord 2022;15:17562864211066751.