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Cognition and mental health

MS and bipolar disorder: understanding the link

The association between multiple sclerosis (MS) and depression is well-established. Are people with MS also at risk of developing bipolar disorder?

Key points

  • Bipolar disorder is significantly more common in people with MS than in the general population.
  • This is not merely a byproduct of the stress of chronic illness; it also has to do with changes in the brain, caused by MS, that affect mood as well as physical function.
  • Mood symptoms may be caused by MS lesions, disease-related inflammation, or medications (steroids in particular).
  • Differentiating ‘primary’ (organic) mania from ‘secondary’ (MS-related) mania is crucial to ensure the correct diagnosis and treatment.
  • Key features that distinguish MS-related mania from organic mania include:
    • Late onset, often after age 35–40 years, or onset associated with MS disease progression
    • Weak or absent family history of bipolar disorder
    • Lack of response to standard treatments for bipolar disorder
  • Treatment for people with MS who experience bipolar disorder is available and effective. With coordinated care, they can successfully manage their symptoms.

MS affects movement, sensation and other bodily functions, but it also impacts the brain systems involved in thinking, emotions and behaviour. Here, I discuss the relationship between MS and bipolar disorder, a mental health condition that causes episodes of unusually high mood (mania or hypomania) and low mood (depression). Bipolar disorder has received less attention than depression in people with MS, despite its substantial effect on quality of life, treatment adherence and prognosis.

For some people with MS, symptoms of bipolar disorder appear for the first time as their disease develops. In others, existing mood symptoms may be made worse by inflammation, brain lesions or medications used to treat MS. This article explains why bipolar symptoms occur in MS, how they may present, how they can be recognised early and how they can be effectively managed.

How common is bipolar disorder in MS?

Research consistently shows that bipolar disorder is more common in people with MS than in the general population. In the general population, bipolar disorder affects roughly 1–2.4% of people. In MS, studies report current and lifetime prevalence rates of about 3% and 8%, respectively. This means people with MS have approximately double or even treble the usual risk.

Importantly, this increased risk is not simply because people with MS interact with healthcare systems more frequently than the general population, which increases the likelihood of mental health conditions being detected (we call this the ‘admission rate’ bias). Nor is it merely a byproduct of the stress of chronic illness (which might explain depression). Large studies that compare people with MS to similar individuals without MS still show a higher rate of bipolar disorder in the MS group. This suggests the association is real and probably related to changes in the brain caused by MS.

What factors cause MS-related mania?

Researchers believe there are three main mechanisms that drive cognitive and behavioural changes in MS; they can occur alone or together.

  • MS lesions that affect mood-regulating circuits
  • inflammation and immune changes
  • treatment-related factors.

Understanding these mechanisms allows clinicians to distinguish MS-related mania from ‘primary’ (organic) psychiatric illness and to deliver appropriate management.

MS lesions that affect mood-regulating circuits

This mechanism disrupts the ‘hardware’ that controls mood. MS causes inflammation and lesions (scarring) in the brain. Areas that are especially important for controlling emotions and behaviour include:

  • the right orbitofrontal cortex (OFC) – involved in regulating social behaviour, judgement and impulse control
  • the temporal lobes – important for memory and emotional processing
  • the white-matter pathways that connect these regions with deeper emotional and reward centres such as the amygdala and thalamus.

If MS lesions interfere with these circuits, the balance between emotional impulses and rational control can be disrupted. This may lead to behaviours that are characteristic of mania, including disinhibition (reduced ‘internal brakes’), uncontrolled emotions, euphoria (unusually elevated mood) and impulsivity. This pattern is sometimes called secondary mania (mania caused directly by a brain condition such as MS).

There is evidence that right-sided frontal or temporal injury leads to mania-like behaviours in other conditions (e.g. stroke, traumatic brain injury, tumours).

Understanding right- and left-sided brain functions

Consistent with literature on secondary mania from stroke or tumours, MS-associated mania is most often associated with right-sided brain lesions. The right hemisphere is dominant for processing negative emotions and withdrawal behaviours, while the left hemisphere processes positive emotions and approach behaviours. A lesion in the right hemisphere may impair the processing of negative emotions, leading to an unopposed ‘positive’ or euphoric affect (‘highs’) driven by the intact left hemisphere.

Inflammation and immune changes

During MS relapses or periods of immune activation, inflammatory molecules disrupt how brain cells communicate (think of it as a disruption to the brain’s ‘software’). One important system involved is the kynurenine pathway, which controls how the body uses tryptophan (an amino acid essential for the creation of compounds such as serotonin and melatonin).

Inflammation increases the activity of an enzyme called indoleamine 2,3-dioxygenase. This shifts tryptophan away from serotonin production towards production of quinolinic acid, a substance that overly stimulates nerve cells through NMDA receptors (N-methyl-D-aspartate receptors). This ‘excitatory overload’ can lead to symptoms like those seen in primary mania, such as agitation, mood instability, sleep disturbance and racing thoughts.

Kynurenic pathway - MS-Selfie gg1

The kynurenine pathway in inflammation-induced pathology of the central nervous system. Activation of IDO in peripheral immune cells (e.g. macrophages) or in the brain leads to production of kynurenine. This is converted to kynurenic acid in astrocytes and to quinolinic acid in microglia. Kynurenic acid can block the release of glutamate and dopamine, contributing to cognitive dysfunction. Quinolinic acid, by contrast, can increase glutamate release, which contributes to neurodegeneration. Figure modified from Haroon et al.

3-HAO, 3-hydroxy-anthranilic acid oxygenase; IDO, indoleamine-2,3-dioxygenase; KAT II, kynurenine aminotransferase II; KMO, kynurenine-3-monooxygenase; NMDA, N-methyl-D-aspartate.

This pathway is one of the clearest biochemical links between MS inflammation and bipolar-type symptoms.

Treatment-related factors

Some medications used in MS influence mood and may contribute to manic symptoms.

Steroids

High-dose intravenous methylprednisolone, typically 1000 mg/day for 3–5 days, is the most common cause of drug-induced mania in MS. Up to 12% of people treated with corticosteroids experience symptoms of mania, and nearly 65% of those with psychiatric side effects present with a mix of mania and psychosis.

A history of prior steroid-induced mood changes, female sex, older age and higher steroid doses increase risk. Steroid-induced mania typically appears 3 − 4 days after starting treatment (median 11 days in some studies) and may involve:

  • severe insomnia
  • pressured speech
  • irritability or agitation
  • grandiosity
  • psychosis in severe cases.

Symptoms usually resolve when the dose is tapered (within roughly 3 weeks), but they can persist longer in individuals with underlying bipolar disorder. I therefore try to avoid treating MS relapses with steroids. However, this is not always possible.

Other agents that may cause mania

  • Amantadine, used for fatigue, can trigger mania in susceptible individuals.
  • Modafinil and methylphenidate, also used for fatigue, have been linked to sudden switching between manic and depressive symptoms.
  • Cannabinoids may destabilise mood or cognition.
  • Interferons more commonly cause depression than mania, but irritability, aggression and mania have been reported. The risk of new psychiatric symptoms is low, and patients with stable mood disorders can usually tolerate interferons with careful monitoring.
  • Fingolimod is linked to mood changes; severe rebound inflammatory activity after discontinuation could theoretically trigger mania.

Diagnosis of MS-related mania

Distinguishing between primary bipolar disorder, secondary MS-related mania and steroid-induced mania can be difficult. Accurate diagnosis is essential for effective management, as treatment for one form may exacerbate another. Below are some of the ‘atypical’ features of MS-related mania that deviate from classic bipolar disorder.

Late onset of symptoms

Primary bipolar disorder usually begins in adolescence or early adulthood. In contrast, secondary mania associated with MS can appear later, often after age 35–40 or during disease progression. A manic or psychotic episode may sometimes be the first manifestation of MS, occurring months or years before a neurological diagnosis.

Mania coinciding with an MS relapse

A sudden change in mood, sleep or behaviour that coincides with new neurological symptoms (e.g. numbness, vision changes, weakness) may indicate that inflammation or new lesions are affecting mood circuits. There may also be evidence of disease progression from MRI scans.

Weak family history

Primary bipolar disorder often runs in families; the absence of a family history suggests a secondary cause (i.e. MS-related pathology).

Disproportionate cognitive decline

Impulse control and executive functions, such as planning, organising and paying attention, are impaired – possibly reflecting frontal lobe involvement.

Mania as an MS relapse

A minority of patients present with isolated psychiatric symptoms (mania, psychosis, delirium) as the only manifestation of a relapse. MRI often reveals new frontal or temporal lesions, even when motor or sensory signs are absent.

Lack of response to standard treatments

Failure to respond to standard mood stabilisers, or paradoxical worsening with antidepressants, warrants a re-evaluation for organic causes.

Genetic considerations

Is the risk solely environmental (inflammation/lesions), or do MS and bipolar disorder share a genetic root? The Major Histocompatibility Complex (MHC) on chromosome 6 is the primary genetic risk factor for MS (specifically the HLA-DRB1*15:01 allele). Interestingly, Genome-Wide Association Studies have suggested that the MHC region is also involved in bipolar disorder and schizophrenia.
There is some evidence that, in certain familial clusters, a gene located near the HLA locus (possibly involving the HLA-DR2 antigen) could confer susceptibility to both autoimmune demyelination and bipolar disorder. Other studies have indicated the opposite: that specific MS risk alleles in the HLA region are associated with decreased schizophrenia risk. The results are therefore mixed; some haplotypes may increase the risk of severe mental illness, while others appear protective against it. It is likely that environmental factors (inflammation, lesion burden) play a greater role than genetics in most cases.

Is the risk solely environmental (inflammation/lesions), or do MS and bipolar disorder share a genetic root? The Major Histocompatibility Complex (MHC) on chromosome 6 is the primary genetic risk factor for MS (specifically the HLA-DRB1*15:01 allele). Interestingly, Genome-Wide Association Studies have suggested that the MHC region is also involved in bipolar disorder and schizophrenia.

There is some evidence that, in certain familial clusters, a gene located near the HLA locus (possibly involving the HLA-DR2 antigen) could confer susceptibility to both autoimmune demyelination and bipolar disorder. Other studies have indicated the opposite: that specific MS risk alleles in the HLA region are associated with decreased schizophrenia risk. The results are therefore mixed; some haplotypes may increase the risk of severe mental illness, while others appear protective against it. It is likely that environmental factors (inflammation, lesion burden) play a greater role than genetics in most cases.

Management

Treatment of MS-related mania depends on the cause.

Steroid-induced mania

If steroids triggered the symptoms, the steroids should be tapered or discontinued if safe.
Short-term antipsychotic medications, such as quetiapine, olanzapine or risperidone, can help stabilise mania symptoms. Quetiapine has the added benefit of aiding sleep, which is commonly disrupted in people with MS. Use of low-dose benzodiazepines during the steroid course can help to reduce the insomnia that often precedes or triggers mania.

Mania caused by MS inflammation

If mania is part of an organic, MS relapse, treating the inflammation is important. High-dose steroids may then be necessary, even though they can in other circumstances cause mania.
This crucial distinction underscores the need for close coordination between neurology and psychiatry.

Mood swings

Lithium is still the gold standard mood stabiliser and is generally safe for psychiatric management in MS. The anticonvulsants valproate, lamotrigine and carbamazepine are useful alternatives in people with MS; they treat both the mania and other MS-related comorbidities, such as neuropathic pain and trigeminal neuralgia.

Managing future steroid treatment

People with a known history of bipolar disorder or steroid-induced instability may benefit from:

  • starting a low-dose mood stabiliser (e.g. lithium) before the steroid course
  • adding an antipsychotic temporarily (e.g. olanzapine)
  • using sleep support (e.g. low-dose benzodiazepines) to prevent insomnia (a common trigger for mania).

Long-term management

Any MS patient presenting with new-onset mania requires a comprehensive workup, including MRI (to check for new frontal/temporal lesions) and a review of recent medication changes, rather than a direct referral to psychiatry. Ongoing coordination between neurologists and psychiatrists is, however, essential. A neurologist might misinterpret mania as ‘euphoria’ related to frontal lobe damage (pseudobulbar affect), while a psychiatrist might miss the neurological signs of an MS relapse that is driving the mood change. Screening tools (e.g. Mood Disorder Questionnaire) may help identify individuals at higher risk but should not replace clinical judgement.

Recognising the distinguishing features of MS-related mania allows clinicians to intervene promptly, reduce misdiagnosis and optimise care. With integrated neurological and psychiatric management, most people with MS experiencing bipolar symptoms can achieve stable, effective control of their mood and maintain a high quality of life.

Reference

Haroon, E et al. Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. Neuropsychopharmacology Rev; 2011:1–26.

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. 

Bladder and bowel, Intimate issues

Female sexual dysfunction in multiple sclerosis

How big is the problem? Can it be effectively managed?

Key points

  • Around 60–70% of women with MS experience sexual dysfunction, including problems with sexual desire and arousal, orgasm, lubrication, sexual satisfaction and pain.
  • The Female Sexual Function Index (FSFI) is a useful online tool for assessing sexual dysfunction in women.
  • Prior to you annual MS review, try to consult recommended resources, such as the FSFI, and list the problems you need to discuss.
  • You may be able to address some of the problems yourself; however, you may need help from your MS team to manage some MS symptoms that affect your sexual functioning.

Prevalence and impact on quality of life

Sexual function is an important aspect of quality of life, and sexual dysfunction in women with MS lessens satisfaction with life, impacting mood and relationships. This affects not only the woman’s own quality of life but her partner’s life as well. Studies and meta-analyses of global prevalence have shown that around 60–70% of women with MS experience sexual dysfunction.1−3 Although it is among the most common complaints of people with MS,1 sexual dysfunction is understudied in both sexes. Less research has been conducted into sexual dysfunction in women with MS, however, compared to men with MS. This is most likely because men with MS benefit from the large body of research into sexual dysfunction outside of MS and have well-established treatments for erectile dysfunction.

Screening for female sexual dysfunction

An example of the MS community neglecting both female and male sexual dysfunction is the observation that the Multiple Sclerosis Impact Scale (MSIS-29), the most used quality-of-life patient-related outcome measure, lacks a question on sexual function.

You can assess whether or not you have sexual dysfunction by downloading and completing the Female Sexual Function Index (FSFI). Based on results from this standardised questionnaire, two out of three women with MS in one study had sexual dysfunction.1 This included problems with sexual desire and arousal (38.6%), orgasm (37.3%), lubrication (23.7%), sexual satisfaction (23.4%) and pain (16.9%).

Your annual review

When preparing for your annual MS review, I recommend completing the FSFI and listing all the problems you think your medical team needs to address. I would also recommend you read the MS Trust’s booklet, ‘Sex, intimacy and MS: a guide for women’; it is exceptional, well thought-out, and a must-read for all women with MS, whether or not you have sexual dysfunction.

From comments made on MS-Selfie, I know that many women with MS worry that sexual intercourse increases the risk of urinary tract infection. Prophylactic urinary antiseptics can help here; you will need to discuss this with your neurologist and/or family doctor to be given a prescription.

Female sexual dysfunction is a tractable problem that needs to be addressed in routine clinical practice and managed accordingly. So, if you are a woman with MS and have sexual dysfunction, don’t simply accept it as your new normal. Work out what your problems are and try to address them yourself; there is a lot you can do for yourself. For many problems, you may need help from your MS team; these include managing the impact of MS symptoms such as depression, anxiety, fatigue, pain, spasticity and bladder or bowel dysfunction. If necessary, patients should be referred to specialist services; that said, few NHS clinics in the UK specialise in female sexual dysfunction.

Cognitive biases

Some time ago, my MS nurse specialist commented that I tended to ask men with MS, but not women, about sexual dysfunction – most likely a cognitive bias on my part, driven by the fact that licensed treatments for erectile dysfunction are available only for men. Now, time permitting, I ask all my patients about sexual dysfunction during their annual review. Sadly, very few admit to having problems, possibly because they feel uncomfortable discussing such matters face-to-face in the clinic when students and visitors are often present. This is why using a pre-clinic screening questionnaire may be a better way of asking about sexual dysfunction.

Priorities for the future

A three-step series of multinational surveys conducted among more than 5000 people living with MS, health care providers, researchers and patient advocacy groups aimed to ascertain the respondents’ priorities for future research in women’s health in MS.4 In the final stages of the study, sexual dysfunction was identified as one of the most important topics for research, after menopause. The priority research questions for sexual dysfunction were to determine the most effective strategies for managing issues around sexual intimacy, including those related to low sexual desire, changes in physical function and MS symptoms.

Many of the issues underlying female sexual dysfunction in MS can be addressed by the MS team, but they will require a much longer consultation than a simple one-liner in an annual review. The real need, in my view, is the establishment of dedicated clinics for female sexual dysfunction, with the necessary multidisciplinary input to address all the problems.

References

  1. Nazari, F et al.  Sexual dysfunction in women with multiple sclerosis: prevalence and impact on quality of life. BMC Urology 2020;20:15.
  2. Salari, N, et al. The global prevalence of sexual dysfunction in women with multiple sclerosis: a systematic review and meta-analysis. Neurol Sci 2023;44:59−66. doi: 10.1007/s10072-022-06406-z.
  3. Yazdani, A et al. Prevalence and risk of developing sexual dysfunction in women with multiple sclerosis (MS): a systematic review and meta-analysis. BMC Womens Health 2023;23:352. doi: 10.1186/s12905-023-02501-1.
  4. Ross, L et al. Priority setting: women’s health topics in multiple sclerosis. Front Neurol 2024;15. doi: 10.3389/fneur.2024.1355817.
Fatigue and insomnia, Sleep disorders

Fatigue in MS – a disabling symptom

Fatigue in MS is common, but it is often not investigated or managed properly. This post highlights the complexity of MS-related fatigue and explains why and how to manage it holistically. 

Key points

  • The different mechanisms underlying MS-related fatigue are explained.
  • The MS disease process, the burden of living with MS, and other factors such as drug side effects, comorbidities and lifestyle choices may all contribute to fatigue in MS.
  • Practical guidance is provided on managing many aspects of MS-related fatigue, using a holistic and systematic approach.
  • Not all fatigue is MS-related; it is important to ascertain if your fatigue could be due to another disease process.

Fatigue is one of the most disabling of all the symptoms of MS. It is the symptom that over 50% of people with MS would most like to be rid of. MS-related fatigue has several underlying mechanisms.

Fatigue caused by MS disease processes

Inflammation in the brain

Inflammatory mediators or cytokines associated with MS – in particular, interleukin-1 (IL-1) and TNF-alpha – trigger ‘sickness behaviour’. This is the response to inflammation that forces us to rest and sleep so that our body can recover. Sickness behaviour is also the body’s response to a viral infection such as flu; in fact, many people with MS describe their fatigue as being like the fatigue they experience with flu. 

Sickness behaviour from an evolutionary perspective is well conserved and occurs in most animals. This type of fatigue needs to be managed by switching off ongoing inflammation in the brain. Many people with MS who take a highly effective DMT report feeling much better and free from fatigue and/or brain fog. This is why recent-onset fatigue that cannot be explained by other factors (see below) may indicate MS disease activity. At present, fatigue on its own does not constitute a relapse.

Many patients with MS who have had COVID-19 tell me that MS-related cog-fog and fatigue feel like the cog-fog and fatigue of COVID-19 and long-COVID. As many as one in four people with long-COVID experience cog-fog, which includes problems in attention, language fluency, processing speed, executive function, and memory: these are the same problems that affect people with MS. 

Cog-fog related to MS and to COVID-19 could be linked to the same inflammatory mechanisms. This syndrome of systemic inflammation causing profound fatigue and cog-fog is not new. Some people with MS who have a systemic infection take weeks or months to return to normal; some patients with more advanced MS never return to their original baseline. This is why, as part of the holistic management of MS, we need to treat and prevent systemic infections as best we can.

The overlap between COVID-19 and MS-related cog-fog raises the question whether both are due to viral infections. There is some evidence of recent Epstein-Barr virus (EBV) reactivation in patients with long-COVID,1 suggesting that the EBV rather than the SARS-CoV-2 may be causing long-COVID symptoms. This is important because chronic EBV infection has been associated with chronic fatigue syndrome. It has also been suggested that chemo-brain is due to similar mechanisms, i.e. chemotherapy triggers CNS inflammation, which causes cog-fog.

Neural plasticity

When parts of the brain are damaged by MS, other areas are co-opted to help take over, or supplement, the function of the damaged area. In other words, people with MS use more brain power than people without MS to complete the same task. This usually manifests as mental fatigue and is why people with MS have difficulty concentrating for prolonged periods and multitasking. At present we have no specific treatment for this type of fatigue, but some patients find amantadine or modafinil helpful. There is also some emerging evidence that fampridine may help with cognitive fatigue. However, preventing damage in the first place should prevent this type of fatigue.

Exercise-related conduction block

Damage to axons that conduct electrical impulses is the reason why people with MS notice their legs getting weaker or another neurological symptom getting worse with exercise. We think this is due to demyelinated or remyelinated axons failing to conduct electrical impulses when they become exhausted. Exercise-induced fatigue is probably the same as temperature-related fatigue; a rise in body temperature also causes vulnerable axons to block and stop conducting. To deal with this type of fatigue we need therapies to promote remyelination and to increase conduction. These types of fatigue are treated by rest, cooling and possibly drugs such as fampridine that improve conduction. At the heart of this type of fatigue is localised energy failure.

Fatigue from living with MS symptoms

Temperature sensitivity

Many people with MS are temperature sensitive. Typically, high temperatures worsen fatigue, but low temperatures also affect some patients. Many people with MS manipulate their behaviour to avoid hot or cold environments. Some find it helpful to use cooling suits, but these are costly and are not covered by NHS funding. Cold or ice baths, swimming and air conditioning can all help with temperature-related fatigue.

Case example

One of my patients had a walk-in butcher’s fridge installed in her house, and she spends 30 minutes there 4 ̶ 5 times a day to manage her fatigue. She is a wheelchair user, and she sits in her wheelchair in the fridge.

Menstrual and menopausal fatigue

Menstrual (or catamenial) fatigue is a form of temperature-related fatigue that occurs in women during the second half of the menstrual cycle when their body temperature increases. It responds to paracetamol and to non-steroidal anti-inflammatory drugs such as ibuprofen and naproxen. Fatigue is a common symptom of menopause too; some women with MS who are menopausal and have fatigue find hormone replacement therapy helpful. 

Whether or not men go through a ‘menopause’ is a moot point. Testosterone levels do drop with age, however, and some male patients find that testosterone replacement therapy helps their MS-related fatigue. In the UK, the indications for testosterone replacement therapy are very well defined and do not include MS-related fatigue, so most people with MS who want to try this therapy need to pay for a private prescription.

Bladder problems

Intermittent waking due to bladder problems may result in fatigue from disrupted sleep. Bladder problems may also contribute to insomnia, with the affected individual needing to visit the bathroom frequently and unable to relax into sleep. For detailed guidance on managing bladder problems, particularly at night, please see the bladder and bowel section of the website, particularly the article on nocturia.  

Insomnia due to pain and discomfort

Other disease-related factors that contribute to fatigue include insomnia from pain, discomfort of being unable to turn in bed and restless legs syndrome (RLS). RLS is common in people with MS, affects sleep quality and is associated with poor cognition. For detailed guidance on managing these MS symptoms, please see the post entitled Sleep disrupted by pain and discomfort.  

A case scenario

“A 28-year-old woman with early relapsing ̶ remitting MS, on glatiramer acetate, and little overt neurological impairment suffers from severe fatigue, which is worse during the latter half of her menstrual cycle. She has recently split up with her long-term partner because of the impact her symptoms have had on her relationship. She has also had to stop working as a bank clerk because of her fatigue.”

Prof G’s response
This patient needs to be examined and will need an MRI and a lumbar puncture to measure her spinal fluid neurofilament levels. If she has evident inflammatory disease activity, her DMT will need to be switched. She needs a full medical assessment, which includes a screen for comorbidities.

The patient complains of cognitive fatigue and, despite not having much physical disability, she was found to have a high brain MS lesion load and noticeable brain volume loss. A formal neuropsychological assessment to establish if she has cognitive impairment would allow her to be referred to a cognitive rehabilitation programme; this can target specific areas to help her cope with her cognitive deficits.

To combat fatigue during her menstrual cycle, this patient did well on naproxen, which is longer acting than ibuprofen and paracetamol. Naproxen only needs to be taken during the second half of her cycle. She was screened for poor sleep hygiene, and she volunteered intermittent early morning waking due to bladder problems and anxiety. Both would need to be addressed as part of her fatigue management programme.

It was clear that the patient had both depression and anxiety, which were related to the impact of MS on her occupational and social functioning. This must be managed with cognitive behavioural therapy (CBT), mindfulness and an exercise programme. If this approach is not helpful, then I would suggest the judicious use of an antidepressant and, failing this, a referral to a psychiatrist and/or psychologist.

Fatigue resulting from other factors

Comorbidities and other diseases

Comorbidities and other diseases related to MS can cause fatigue and should be screened for. These include infections (see above). In people with more advanced MS, the urinary tract is most often affected, but other sites of infection include the sinuses, teeth, lungs, skin (intertrigo and pressure sores) and bowels.

Fatigue is common with thyroid disease; an underactive thyroid gland (hypothyroidism) and an overactive gland (hyperthyroidism, or thyrotoxicosis) cause fatigue. Diabetes, other endocrine (hormonal) problems, anaemia and heart, kidney, liver or lung diseases all cause fatigue.

Side effects of drugs

Fatigue is a common side effect of many medications, particularly drugs that cause sedation and some DMTs. Flu-like side effects from interferon-beta, for example, may make fatigue worse. Anticholinergics and antispasticity drugs are sedating, blunt cognition and may worsen MS-related fatigue. If you have fatigue, therefore, it is important to review your medications. MS is associated with polypharmacy, but some of the medications that cause or exacerbate fatigue can be reduced in dose, stopped or potentially replaced with alternatives that don’t exacerbate fatigue.

Lack of sleep and/or sleep disorders

Poor sleep means you feel tired in the morning. Most people with MS have poor sleep hygiene and almost half have an actual sleep disorder. A clue to this is how you feel in the morning and whether you have excessive daytime sleepiness. If you wake up in the morning and don’t feel refreshed and/or you fall asleep frequently during the day, you need a formal sleep assessment. You can complete the Epworth Sleepiness Scale online to see if you have a problem.

Depression and anxiety

Fatigue is a common symptom of depression and anxiety. Of the many online screening tools for depression and anxiety, the best one to use if you have MS is probably the Hospital Anxiety and Depression Scale (HADS). 

Obesity

Being overweight requires additional energy to perform physical tasks, and obesity itself causes fatigue. Recently an association has been found between obesity and depression. Obesity also predisposes you to sleep disorders; obese people with MS are more likely to have obstructive sleep apnoea. For all these reasons you should engage with lifestyle and wellness programmes to manage obesity and fatigue. 

Deconditioning

Deconditioning is simply the term we use for being unfit. If you are unfit, performing a demanding physical task makes you tired. Deconditioning is treated with exercise, which paradoxically can reduce fatigue. Patients may claim that exercising makes their fatigue worse. Yes, that does happen, but if you persevere and get fitter your fatigue often improves. The important thing is to start a graded exercise programme and build up slowly. Exercise does some incredible things to the brain, many of which explain why it is effective at treating not only fatigue but also depression and anxiety. Exercise is a form of ‘disease-modifying therapy’ and hence everyone with MS should be participating in an exercise programme. 

Poor nutrition and ‘food coma’

Some people with MS are anorexic and eat very poorly; as a result, they have little energy. Although this is quite rare, I have had a few such patients over the years. Similarly, overnutrition may have the same effect. Some of the hormones your gut produces cause you to feel tired and want to sleep; this is the so-called siesta effect (also referred to as food coma or postprandial hypersomnolence). Reducing the size of your meals and changing your eating behaviour may improve this. Postprandial hypersomnolence has two components.

  1. A state of perceived low energy related to activation of the parasympathetic nervous system (which is part of the autonomic nervous system) in response to expansion of the stomach and duodenum from a meal. In general, the parasympathetic nervous system slows everything down. 
  2. A specific state of sleepiness triggered by the hormone cholecystokinin that helps digest food and regulate appetite. It is released in response to eating and to changes in the firing and activation of specific brain regions. The coupling, or interaction, of digestion and the brain is referred to as ‘neurohormonal modulation of sleep’ and it underlies the reflexes responsible for postprandial hypersomnolence. There is therefore a well-studied biological reason why we feel sleepy after eating a meal. 

Managing food coma – practical tips

The first patient who alerted me to the problem of food coma in MS was so affected by postprandial hypersomnolence that she now eats only one meal a day, late in the evening. She can then ‘crash’ and go to sleep about an hour after eating. She needs to be functional during the day but cannot do her professional work if she eats anything substantial during working hours because of her overwhelming desire to sleep. She has tried caffeine, modafinil and amantadine to counteract postprandial hypersomnolence, but all these substances had only a small effect.

Other patients reporting postprandial hypersomnolence derive some benefit from the judicious use of stimulants. You can start by self-medicating with caffeine, but this may have the drawback of worsening your bladder function. Please note, however, that it is not advisable to take stimulants later than about 3 pm or 4 pm because they have a long half-life and can cause insomnia.

Some patients find carbohydrate-rich foods particularly potent at inducing ‘food coma’. Indeed, glucose-induced insulin secretion is one of the drivers of this behavioural response. This may be why people who fast or eat very low-carbohydrate or ketogenic diets describe heightened alertness and an ability to concentrate for long periods. Another option is to reduce your meal size: instead of large meals, try eating multiple small snacks during the day.

Exercise has helped some patients deal with postprandial hypersomnolence. I am not sure exactly how exercise works – possibly by lowering glucose and insulin levels and improving insulin sensitivity. The latter will reduce hyperinsulinaemia, which not only causes postprandial hypersomnolence but is an important driver and component of metabolic syndrome and obesity.

Postprandial hypersomnolence will be worse if you already suffer from a sleep disorder and excessive daytime sleepiness. Most people with MS have a sleep disorder, so there is little point in focusing on postprandial hypersomnolence and ignoring the elephant in the room.

Using your energy effectively

One strategy to manage MS-related fatigue is to imagine your energy levels as a battery, i.e. you have only so much energy in the day. People with MS have smaller batteries than people without MS and therefore need to plan their day and activities to maximise their use of energy. For example, if you do something tiring in the morning, you should rest in the afternoon to conserve energy for evening activities. Similarly, if you find some activities very tiring, such as taking a hot shower or bath, plan to do this in the evening before bed.

Conclusion

It is apparent from this discussion that fatigue in MS is more complex than we realise. So be careful, or at least wary, if your neurologist simply wants to reach for the prescription pad to get you out of the consultation room. Any MS-related symptoms that can affect sleep need to be managed accordingly. Like other MS-related problems, a holistic and systematic approach is needed to manage and treat MS-related fatigue correctly. Not all fatigue is MS-related. This is why it is important to take a step backwards and ask yourself if your fatigue could be due to another disease process.

Reference

  1. Gold JE et al. Investigation of long COVID prevalence and its relationship to Epstein-Barr virus reactivation. Pathogens 2021;10:763.
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.
DMTsSafety, Monitoring MS

How can I reduce my chances of adverse events on specific DMTs?

The complications associated with immunosuppression vary from DMT to DMT. You will find it helpful to understand what investigations to expect before and during treatment and how these may vary depending on the DMT(s) you are considering.

Key points

  • Numerous tests are carried out at the start of your treatment (baseline); these include blood, urine and tests for a range of infections.
  • Some patients will need tests or procedures specific to their DMT that are inappropriate for everyone with MS – for example, vaccination against some infections; pregnancy and/or genetic counselling; prevention of cardiovascular complications; and management of infusion reactions.
  • Ongoing monitoring is required for many but not all of the above factors.
  • All licensed MS DMTs have had a thorough risk ̶ benefit assessment, and their benefits are considered to outweigh the potential risks.

Standard tests … and why we do them

If you have read the article on immunosuppression, you will know that immunosuppressive DMTs may reduce white blood cell counts and antibody responses to vaccines and increase the likelihood of some infections and cancers. However, we can reduce the risk of many complications associated with long-term immunosuppression (we use the shorthand ‘de-risk’). This article explains what needs to be done at the start of DMT administration (baseline) and during subsequent monitoring. The specifics, however, vary from DMT to DMT.

Baseline tests

Tests at baseline (before starting DMT administration) include full blood count, platelets, liver, kidney and thyroid function tests, and a urine screen. Recording baseline immunoglobulin levels is particularly important if you are about to start an anti-CD20 therapy (ocrelizumab, ofatumumab or rituximab) so that we have a reference level for future comparisons. 

Serum protein electrophoresis is done for patients considering starting interferon-beta; having a so-called monoclonal gammopathy (an abnormal immunoglobulin) is a contraindication to starting an interferon-beta formulation in people with MS. The drug has been associated with a form of capillary leak syndrome, leading in rare cases to death from an adult respiratory distress syndrome.

The table below summarises the routine investigations required at baseline; subsequent sections provide further detail.

Tests routinely carried out at the start of treatment (baseline).
AHSCT, autologous haematopoietic stem cell transplantation; CMV, cytomegalovirus; CSF, cerebrospinal fluid; DMT, disease-modifying therapy; EBV, Epstein ̶ Barr virus; ECG, electrocardiogram; FBC, full blood count; HIV, human immunodeficiency virus; HPV, human papillomavirus; JCV, JC virus; LFTs, liver function tests; MMR, measles/mumps/rubella; MRI, magnetic resonance imaging; PCP, pneumocystis pneumonia; PML, progressive multifocal leukoencephalopathy; TB ELISpot, tuberculosis enzyme-linked immune absorbent spot; TFTs, thyroid function tests; U&E, urea and electrolytes; VZV, varicella zoster virus.

Infection screening

At our centre, we screen for a relatively large number of infectious diseases so that we can treat any subclinical infection before starting a DMT. This is particularly relevant for HIV-1 and 2, hepatitis B and C, syphilis and tuberculosis (TB).  

Screening for the JC virus (JCV), which causes progressive multifocal leukoencephalopathy (PML), is only really needed for people with MS considering starting natalizumab. Even if you are JCV positive, you can be treated with natalizumab for 6 ̶ 12 months and sometimes longer if you are prepared to take on the risk of PML and the extra monitoring required to detect PML early. 

We only check measles/mumps/rubella (MMR) status in patients without documentation of full vaccination as children. We check varicella zoster virus (VZV) status before starting immunosuppression and vaccinate seronegative individuals. Currently, we are still using the live VZV vaccine. This will change, and we will likely be offering all people with MS in the UK the component inactive VZV vaccine (Shingrix, that has had its licence extended) to reduce the chances of zoster reactivation in all adults starting immunosuppression. This new Shingrix indication is similar to the pneumococcal vaccine (Pneumovax). Our centre is only recommending Pneumovax in patients about to start an anti-CD20. However, when Shingrix becomes available on the NHS, it will make sense to bundle this with the Pneumovax and make it routine for all people with MS before starting immunosuppressive therapy. Please check with your healthcare team which products are available locally.

Routine tests and monitoring for Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are only needed for subjects undergoing autologous haematopoietic stem cell transplantation (AHSCT), which causes profound short-term immunosuppression that can result in CMV and EBV reactivation. CMV reactivation also occurs with alemtuzumab, so this needs to be considered when investigating patients who develop complications after receiving alemtuzumab (please see Opportunistic infection in MS). 

For patients starting long-term immunosuppression, it is advisable to screen for active human papillomavirus (HPV) infection (by cervical smear or vaginal swab) and for warts or active infection with molluscum contagiosum. Warts are caused by HPV skin infection; molluscum contagiosum is due to a relatively benign pox virus that typically affects young children but occasionally affects adults. Warts and molluscum contagiosum can spread rapidly in patients receiving alemtuzumab, so I recommend treating these skin infections before starting immunosuppression for MS. 

Vaccinations

We encourage all patients to be vaccinated against COVID-19 and seasonal flu; outside the flu vaccine season, we remind people to get vaccinated during the next vaccine season. 

Hepatitis B, meningococcal and Haemophilus influenzae vaccines are considered only for people with MS who are at high risk of infection and have not had these vaccines as part of a national vaccine programme, i.e. healthcare and laboratory workers for hepatitis B, school and university students and military recruits for meningococcal vaccine and paediatric patients for Haemophilus influenzae. 

The issue around having the HPV vaccine as an adult is more complex. For example, in the UK, the NHS does not cover the cost of the vaccine for people over 25. In addition, most people have only had the quadrivalent vaccine (Gardasil-4), which covers about two-thirds of the strains that cause cancer. Some people with MS may want to upgrade their immunity with the polyvalent vaccine (Gardasil-9) that covers over 95% of the cancer-causing strains of HPV. For more information on HPV vaccination, please see Case study: cervical intraepithelial neoplasia (CIN) and ocrelizumab.

MMR is a live vaccine given in childhood (see MMR vaccine: to vaccinate or not? ). Owing to vaccine hesitancy, however, many people do not receive this vaccine as children. Therefore, if an adult with MS is about to start immunosuppressive therapy and has not been vaccinated against MMR, we advise them to do so. This is particularly important for people about to start natalizumab because these viruses are neurotropic and can infect the brain. Natalizumab blocks immune response within the brain; hence, exposure to a neurotropic virus could cause serious infection, similar to what we see with the JC virus – which causes PML.

Travel vaccines for people who travel as part of their work or plan to travel shortly need to be considered. In particular, the yellow fever vaccine is a live vaccine (made from a weakened yellow fever virus strain) and it should ideally be given before someone starts on immunosuppressive therapy. 

Cardiovascular screening

You may need an ECG (electrocardiogram), to rule out an abnormal heart rhythm or electrical conduction abnormality and to check your left ventricular function (ejection fraction). These abnormalities are a relative contraindication to using the S1P modulators (fingolimod, siponimod, ozanimod, ponesimod), which may affect the conduction of the heart. In patients treated with mitoxantrone, the left ventricular ejection fraction (LVEF) must be done at baseline and regularly monitored because mitoxantrone is toxic to the heart. If the LVEF drops significantly, further dosing of mitoxantrone is contraindicated. 

Pregnancy, family planning and genetic testing

Many chemotherapy agents used in AHSCT for ablating (extracting) the bone marrow are toxic to the ovaries and testes. Therefore, patients receive counselling before treatment and can have eggs (oocytes) or sperm banked for future use. Egg banking is also a consideration for women with MS being treated with mitoxantrone. Men receiving mitoxantrone do not need to bank sperm, however, because mitoxantrone does not cross the testes ̶ blood barrier. 

Genetic testing is only required at present if you wish to receive siponimod. Siponimod is metabolised by a specific liver enzyme (biological catalyst) with two functional variants – slow metabolising and fast metabolising. People who carry two slow-metabolising variants of the enzyme cannot receive siponimod. Intermediate metabolisers (those that carry one slow- and one fast-metabolising version of the enzyme) receive low-dose siponimod, while those with two fast-metabolising enzymes receive high-dose siponimod. 

Protecting against progressive multifocal leukoencephalopathy

I have included magnetic resonance imaging (MRI) and lumbar puncture with cerebrospinal fluid (CSF) testing for JCV among the baseline tests. This is specific to patients at high risk of developing PML who are switching from natalizumab to a depleting immune reconstitution therapy such as alemtuzumab or another therapy that depletes their immune system (e.g. cladribine or an anti-CD20 therapy). These tests are done to exclude asymptomatic PML, which will otherwise be carried over to the new treatment. The effects of these immunosuppressive therapies on your immune system cannot be rapidly reversed, which is a problem because immune reconstitution is needed to clear PML. Most MS centres do not mandate CSF testing in this situation because it does not always reveal the presence of PML. However, I still request this test on my patients to gain as much information as possible on which to base potentially life-changing decisions.

Prophylactic antivirals and antibiotics

Patients in our centre undergoing AHSCT or receiving alemtuzumab will be given antivirals and antibiotics to reduce the likelihood of certain infections. This is particularly relevant for listeriosis, which is a rare infection transmitted via food. We also encourage all our patients to start and maintain a specific diet to reduce the chances of listeriosis. The risk of listeriosis is only present for a short period when both the adaptive and innate immune systems are compromised, that is, for 4 weeks after receiving alemtuzumab, so we recommend antibiotic prophylaxis for 4 weeks. Our online resource provides more information about listeriosis. If you live in the UK, you can order our free listeriosis prevention kit, which contains a booklet (also downloadable) and various practical items to help keep you safe.

Strategies for limiting the risks from immune reconstitution therapies and infusion DMTs.

Infusion reactions

When you use agents that cause cell lysis (breakdown), such as alemtuzumab and intravenous anti-CD20 therapies, the contents of cells cause infusion reactions. To prevent such reactions or reduce their severity, we pretreat patients with corticosteroids, antihistamines and antipyretics. The exact protocols for each DMT differ; for example, ocrelizumab infusion reactions are generally only a problem with the first and second doses; therefore, many centres don’t give steroids with the third and subsequent infusions. The latter was particularly important during the COVID-19 pandemic when it was shown that the recent administration of high-dose steroids increased your chances of severe COVID-19. 

Ongoing monitoring

Once someone has been treated with a DMT, ongoing monitoring is required. What gets monitored and how frequently depends on the individual DMT. For a list of DMTs associated with important adverse events, please see our summary Table in ‘De-risking’ guide: monitoring requirements of individual DMTs.

The regulatory authorities usually put in place specific monitoring requirements, which can differ worldwide. It is important that you also enrol in your national cancer screening programmes. Being on chronic immunosuppression increases your chances of developing secondary malignancies, so please remain vigilant. 

Tests carried out regularly as part of ongoing monitoring.
FBC, full blood count; LFTs, liver function tests; MRI, magnetic resonance imaging; PML, progressive multifocal leukoencephalopathy; TFTs, thyroid function tests; U&E, urea and electrolytes.

I want to reassure you that all licensed MS DMTs have undergone a thorough risk ̶ benefit assessment by the drug regulators, and the benefits of these treatments are considered to outweigh the potential risks. On balance, the level of immunosuppression associated with MS DMTs is typically mild to moderate; hence, the complications are relatively uncommon. MS is a serious disease and, if left to run its natural course, would result in most patients becoming disabled. To learn more about the natural course of MS, please read the section entitled What are the consequences of not treating MS?

DMTsSafety, Monitoring MS

‘De-risking’ guide: monitoring requirements of individual DMTs

Before you start taking a disease-modifying therapy (DMT), your MS team will carry out routine tests and investigations, many of which are repeated during subsequent monitoring or before switching to another DMT. The regulatory authorities that license the drugs specify their monitoring requirements. What gets monitored and how frequently depends on the individual DMT.

All licensed MS DMTs have undergone a thorough risk ̶ benefit assessment by the drug regulators, and the benefits of these treatments are considered to outweigh the potential risks. The table below summarises the main monitoring requirements of individual DMTs or DMT classes. For more detailed information, see the post on reducing your chances of adverse events.

AHSCT, autologous haematopoietic stem cell transplantation; CMV, cytomegalovirus; CSF, cerebrospinal fluid; EBV, Epstein ̶ Barr virus; ECG, electrocardiogram; HPV, human papillomavirus; JCV, JC virus; LVEF, left ventricular ejection fraction; MRI, magnetic resonance imaging; PML, progressive multifocal leukoencephalopathy.