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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

Male sexual dysfunction in multiple sclerosis

Sexual dysfunction is a common symptom in men with MS, with a prevalence that surpasses that seen in the general population and other chronic disease states. Despite sexual dysfunction being one of the most frequently overlooked and under-addressed MS symptoms, it seldom gets documented and treated in men with MS.

Key points

  • Many men with MS experience some form of sexual difficulty; however, this important aspect of overall well-being is underdiagnosed and undertreated.
  • Such difficulties usually result from a combination of neurological, psychological, social and cognitive factors.
  • Primary dysfunction, caused by damage to the network of signals between the brain, spinal cord and peripheral nerves, can affect the ability to achieve an erection, orgasm or ejaculation; it may also adversely affect libido, sexual desire and genital sensation.
  • Secondary dysfunction results from other MS-related symptoms, including fatigue, spasticity, pain, weakness, bladder dysfunction and bowel dysfunction. Many of the medications used to manage such symptoms may cause or worsen sexual difficulties.
  • Tertiary dysfunction refers to the psychological, emotional and interpersonal challenges of living with MS: depression, anxiety, low self-esteem and impaired body image are among the factors that impact sexual desire and confidence.
  • Management of male sexual dysfunction requires a coordinated, multidisciplinary and personalised approach that involves the MS team, a urologist, physiotherapist, occupational therapist and a psychologist or sex therapist.
  • A wide range of medications, interventions and lifestyle modifications are available that can help couples affected by MS to adapt to the current reality and build a new, satisfying form of intimacy.

An overlooked and distressing symptom

Sexual dysfunction is a common symptom in men with MS, with a prevalence that surpasses that seen in the general population and other chronic disease states. Most studies report that 50–90% of men living with MS will experience some form of sexual difficulty during their disease course. Despite this, sexual dysfunction is one of the most frequently overlooked and under-addressed MS symptoms, and it seldom gets documented and treated in men with MS. This is a clinical paradox, an example of a ‘conspiracy of silence’ where both parties in the clinical encounter overlook a significant issue affecting quality of life.

The main reasons why sexual dysfunction in men with MS is under-recognised, underdiagnosed and undertreated are the taboos of discussing it in the clinic, both from the patient and the HCP perspective. Surveys reveal that the primary barriers to discussing sexual health on the part of HCPs include:

  • time constraints during appointments
  • the major problem that the issue is ‘outside of my role’
  • lack of professional training
  • perceived patient discomfort.

Concurrently, patients are often reluctant to initiate these conversations owing to embarrassment, shame or a deeply held belief that sexuality is somehow incompatible with having a disability. This disconnect between the reality of the patient experience and the focus of the clinical consultation means that a treatable condition that causes significant distress is often left to fester, impacting mental health and relationships. 

Far from being a peripheral concern, sexual function and sexual health are essential components of overall well-being. In men with MS, the onset of sexual dysfunction often precipitates a decline in quality of life, negatively affecting mood, self-esteem and intimate relationships. The distress frequently extends beyond the individual, impacting partners and contributing to marital conflict. The enquiry below illustrates the distress experienced by one man who contacted me for advice; his experience is not uncommon, unfortunately.

Case example

I am a 30-year-old man with relapsing MS. I was diagnosed during my first year of University, aged 18. I presented with transverse myelitis, weakness of both legs and urinary retention. I have been on natalizumab for 12 years and have done very well. However, I have sexual problems with difficulty getting and maintaining an erection. This is affecting my relationship with my wife. Whenever I bring this up with my MS nurse or neurologist, I get dismissed. My GP has given me Viagra, which helps, but its effects are unpredictable, and it often lets me down. I have gotten to the point where I now avoid sexual activity. What advice can you give to help me and others like me?

A complex range of causes

The underlying causes (aetiology) of sexual dysfunction in men with MS are usually complex, variable and dynamic. Some men with MS experience sexual dysfunction as part of a relapse, and they recover with time. However, sexual dysfunction in men with MS usually results from a combination of neurological, psychological, social and cognitive factors. It is therefore vital to approach it from three different perspectives.

  1. Primary dysfunction arises directly from MS lesions within the central nervous system that disrupt the neural pathways governing sexual response.
  2. Secondary dysfunction is the consequence of other MS symptoms, such as fatigue, pain, spasticity, or bladder and bowel issues, which create physical barriers to sexual activity.
  3. Tertiary dysfunction encompasses the psychosocial, emotional and cultural issues that stem from living with a chronic illness, including depression, altered body image and changes in relationships.

Clinical presentations of male sexual dysfunction

Erectile dysfunction

This is the most commonly and widely studied sexual problem in men with MS. Defined as the consistent inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance, erectile dysfunction (ED) affects a large majority of men with MS who report sexual issues, with some estimates as high as 80%. Across the entire male MS population, approximately 70% experience erectile problems at some point after an MS diagnosis.

Ejaculatory and orgasmic dysfunction

While ED receives the most attention, disorders of ejaculation and orgasm are also common and can be even more distressing for patients owing to a lack of effective treatments. Studies estimate that 35–50% of men with MS experience problems with ejaculation. The Male Sexual Health Questionnaire is used as a screen for dysejaculation. Ejaculatory disorders manifest as:

  • delayed ejaculation or anejaculation: difficulty or complete inability, respectively, to ejaculate despite adequate stimulation
  • premature ejaculation: climaxing too rapidly for sexual satisfaction
  • anorgasmia: the failure to reach orgasm
  • altered orgasmic sensation: a less intense or less pleasurable orgasmic experience.

Disorders of libido or sexual desire

A diminished or absent interest in sex is another crucial component of sexual dysfunction in men with MS. Though less rigorously studied than ED, one report suggests that reduced libido affects approximately 40% of men with MS. Loss of libido is particularly complex, often arising from a combination of damage to the brain’s centres that impact desire, the secondary effect of fatigue, and tertiary psychological factors like depression and anxiety.

Altered genital sensation

The direct neurological impact of MS can manifest as abnormal sensations in the genital area, including numbness (decreased sensation), paraesthesias (e.g. pins and needles) or dysaesthesias (unpleasant or painful sensations, such as burning). These sensory disturbances can fundamentally alter the experience of sexual touch, making it less pleasurable or even painful, thereby directly interfering with arousal and orgasm.

The focus on ED in both MS research and clinical practice is driven in part by the availability of effective pharmacological treatments for this issue; this creates an incomplete picture of the patient’s experience. A management plan that successfully restores erectile function, for example, but fails to address a co-existing inability to ejaculate or a profound lack of sexual desire will ultimately fail to improve the patient’s overall sexual satisfaction and quality of life. A thorough clinical evaluation that assesses all phases of the sexual response cycle is therefore needed.

Functional changes underlying male sexual dysfunction in MS

Primary dysfunction

Normal human sexual function is a complex process that requires the integration of signals between the brain, spinal cord and peripheral nerves. MS damages this network in several ways, causing primary sexual dysfunction.

Cerebral and brainstem lesions

MS lesions in the brain and brainstem affect libido, arousal and orgasm.

  • Libido and arousal: Sexual desire is not merely a hormonal process; it originates in the brain. Lesions in higher cortical areas, particularly the limbic system (the brain’s emotional centre) and the hypothalamus, can diminish libido and impair the capacity to process sensory or psychological cues as erotic. MRI studies have correlated dysfunction in arousal and erection with lesions in specific brain regions, including the frontal lobe, prefrontal cortex, temporal lobe, insula and hippocampus.
  • Orgasm: Orgasm is also vulnerable to cerebral damage, and orgasmic dysfunction is associated with lesions in the pons (part of the brainstem), left temporal lobe and right occipital areas.

Spinal cord lesions

The spinal cord relays neuronal signals from the brain to the genitals and transmits sensory information back up to the brain. Lesions along the spinal tracts are the leading cause of ED and ejaculatory disorders.

  • Erectile function: Penile erection is a neurovascular phenomenon mediated by two distinct pathways, both of which can be compromised by MS. A psychogenic erection, initiated by erotic thoughts or sensory stimuli processed by the brain, depends on intact nerve signals travelling down the spinal cord to the pelvic organs. A reflexogenic erection, triggered by direct physical touch to the genitals, relies on a reflex arc located in the sacral segments of the spinal cord (S2−S4). MS lesions can disrupt these pathways individually or in combination. Consequently, depending on the specific location of the spinal damage, a man might be able to achieve an erection from direct touch but not from psychological arousal, or vice versa.
  • Ejaculation: Ejaculation is a far more complex reflex than erection, involving the coordinated contraction of multiple pelvic muscles and requiring precise, intact communication between the brain and the entire length of the spinal cord. This complexity makes it exceptionally vulnerable to disruption by MS lesions, which helps explain why ejaculatory problems in MS are so common and difficult to treat.

Autonomic and hormonal factors

The autonomic nervous system, which controls involuntary bodily functions, plays a pivotal role in regulating erection and ejaculation. MS can cause autonomic dysfunction, further contributing to these problems. Additionally, emerging evidence suggests that chronic inflammation associated with MS, as well as hypothalamic lesions, can disrupt the hypothalamic-pituitary-gonadal axis. This can lead to altered levels of sex hormones, such as testosterone, and has even been linked to impaired sperm quality.

Secondary dysfunction

Secondary sexual dysfunction arises from other MS-related symptoms and the side effects of medications used to treat these symptoms.

  • Fatigue: Fatigue is one of the most common and disabling MS-associated symptoms that directly undermines sexual function by reducing the physical energy and motivation required for intimacy. When daily life is already exhausting, sexual activity can feel like an insurmountable task.
  • Spasticity, pain and weakness: Spasticity, chronic pain, and muscle weakness can make movement difficult and some sexual positions uncomfortable or impossible. Painful muscle spasms can be triggered by the movements of sexual activity, leading to a conditioned avoidance of sex.
  • Bladder dysfunction and bowel dysfunction: The fear of urinary or faecal incontinence during sexual activity is a potent psychological deterrent. With more than 50% of people with MS experiencing bladder and bowel issues, this is a widespread concern. The anxiety and embarrassment associated with a potential accident can cause individuals and their partners to avoid physical intimacy altogether.
  • Side effects of medication: Many of the medications prescribed to manage the symptoms of MS can, ironically, cause or exacerbate sexual dysfunction. Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, are well known for causing decreased libido, ED and anorgasmia. Similarly, medications for spasticity, neuropathic pain and urinary frequency can also interfere with sexual responses.

Tertiary dysfunction

Tertiary dysfunction refers to the complex web of psychological, emotional and interpersonal challenges that arise from living with a chronic, unpredictable illness like MS. These factors can be just as debilitating to a person’s sexual health as any physical symptom.

  • Depression and anxiety: There is a strong, two-way, destructive relationship between MS, depression and sexual dysfunction. Depression affects 30–50% of individuals with MS, and it is an independent predictor of sexual dysfunction. The experience of sexual failure can, in turn, trigger or worsen feelings of depression, despair and isolation, creating a vicious cycle that is difficult to break.
  • Body image and self-esteem: The physical changes brought on by MS – such as a limp, the need for a cane or wheelchair, weight gain from steroids or inactivity, or tremors – can profoundly damage a man’s body image and sense of masculinity. This may lead to feelings of being ‘flawed’, ‘broken’ or ‘unattractive’ that erode self-esteem and sexual confidence.
  • Relationship dynamics and role changes: MS does not just affect the individual; it impacts the entire relationship. Performance anxiety and fear of rejection can lead to avoidance of intimacy. A particularly challenging dynamic arises when an intimate partner must assume significant caregiving responsibilities. This ‘role reversal’ can blur the lines between lover and caregiver, disrupting the emotional foundation of the sexual relationship. The partner’s own sexual satisfaction and quality of life are also frequently diminished, highlighting the two-way nature of sexual dysfunction.

Management of male sexual dysfunction in MS

A single treatment approach towards sexual dysfunction in MS often fails because it is a multifactorial problem that requires a coordinated, multidisciplinary approach. This includes the MS team, a urologist, a physiotherapist, an occupational therapist and a psychologist or sex therapist. Failure to implement an interdisciplinary approach is usually because the MS team is reluctant to initiate the conversation about sexual health or lacks knowledge.

Before any medication or therapy is initiated, it is essential to break the ‘conspiracy of silence’ and create a safe, confidential environment for open communication between the patient, their partner and the healthcare provider. For the MS HCP, this involves routinely and proactively asking about sexual health as part of a holistic review of systems, often alongside questions about bladder and bowel function. For the patient, having ‘permission’ to discuss these sensitive issues can be profoundly therapeutic, reducing shame and ‘validating’ their experience as a legitimate medical concern.

Management of primary sexual dysfunction

Pharmacotherapy for erectile dysfunction

  • Oral phosphodiesterase-5 (PDE-5) inhibitors: Medications such as sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra) and avanafil (Spedra) are the first-line pharmacological treatments for ED in men with MS. Vardenafil is generally not available on the NHS, and avanafil is prescribed via specialist sexual dysfunction clinics. Sildenafil (Viagra) has a short half-life and needs to be taken before intercourse is planned. In comparison, tadalafil (Cialis) has a long half-life and is called the weekend Viagra. Some men with MS find that combining the two drugs is synergistic. Please note that they come in different doses, so you will need to titrate the dose to find the one that works best for you. These drugs do not create an erection spontaneously; they work by enhancing the natural erectile process, increasing penile blood flow in response to sexual arousal. Clinical trials have demonstrated their efficacy, but they may be effective in only about 50% of men with MS (a lower rate than in the general population), likely due to the underlying neurological deficits. These drugs are contraindicated in men taking nitrate medications for heart conditions.
  • Injectable and intraurethral medications: For men who do not respond to or cannot take oral PDE-5 inhibitors, these locally administered medications are highly effective second-line options. Alprostadil, a synthetic prostaglandin, can be injected directly into the erectile tissue of the penis (intracavernosal injection) or inserted as a small suppository into the urethra. These methods induce an erection directly and are often successful when oral agents are not.

Management of ejaculatory and orgasmic disorders

This remains an area of unmet clinical need, as there are currently no medications specifically approved or consistently effective for treating delayed ejaculation or failure to reach orgasm (anorgasmia) in MS. Some antidepressants (e.g. SSRIs) may be used ‘off-label’ to treat premature ejaculation thanks to their side effect of delaying orgasm. For delayed ejaculation or anorgasmia, the focus shifts to enhancing stimulation through manual or oral techniques or with the use of assistive devices like penile vibrators.

Addressing low libido and sensory changes

A review of the patient’s current medications is needed because many drugs, especially SSRIs, can suppress libido. Switching to an alternative antidepressant with a more favourable sexual side effect profile, such as bupropion or certain SNRIs (serotonin and norepinephrine reuptake inhibitors), may be beneficial. If blood tests reveal low testosterone levels, hormone replacement therapy may be considered to improve desire and energy. For altered genital sensation, the goal is to compensate for the diminished nerve signals by increasing the intensity and focus of stimulation using vibrators, different types of touch, or other sexual aids.

Management of secondary sexual dysfunction

  • Fatigue: Energy conservation is paramount. This involves planning sexual activity for times of day when energy is highest (often the morning), taking a nap beforehand, and collaborating with a partner to find less physically demanding sexual positions, such as spooning.
  • Spasticity: Proactive management can prevent painful muscle spasms from disrupting intimacy. This may include gentle stretching or massage before sex, taking an antispasticity medication like baclofen approximately 30–60 minutes before sexual activity, and/or experimenting with positions that minimise muscle tightness and discomfort.
  • Bladder and bowel issues: Careful planning can alleviate the anxiety surrounding potential incontinence. Strategies include restricting fluid intake for a few hours before sex, ensuring the bladder and bowel are emptied immediately beforehand and using intermittent self-catheterisation if needed. Using a condom can also provide a sense of security against urinary leakage.
  • Cognitive changes: For individuals whose concentration is affected by MS, creating an environment conducive to focusing is helpful. This means minimising external distractions, such as television or phones, and maximising sensual stimuli, including lighting, music and scent, to help maintain focus on the intimate experience.

Psychological counselling and sex therapy are the cornerstone of a holistic management plan and include cognitive behavioural therapy (CBT). CBT can be effective for challenging and reframing the unhelpful thoughts and beliefs that fuel performance anxiety and negative body image. Couples counselling provides a structured forum to improve communication, openly discuss fears and frustrations, and collaboratively explore the changes MS has brought to the relationship, including the sensitive shift from partner to caregiver.

Sensate focus and body mapping are specific sex therapy techniques that are particularly valuable for couples affected by MS. These exercises involve non-demand, non-goal-oriented sensual touching, shifting the focus away from intercourse and orgasm and toward the rediscovery of pleasure. This is especially important when genital sensation has been altered, as it helps couples identify new erogenous zones and broaden their definition of intimacy.

Rehabilitation and lifestyle interventions

These approaches focus on improving physical function and overall health to support sexual well-being.

Pelvic floor exercises are crucial for maintaining erectile rigidity and for the muscular contractions associated with ejaculation. A specialised physiotherapist can design an exercise programme (for example, Kegel exercises) to strengthen these muscles, potentially improving erectile and ejaculatory control. While much of the research into pelvic floor training has focused on women, the principles are also directly applicable to men.

General health has a direct impact on sexual function. Lifestyle modifications such as adopting a heart and brain-healthy diet, engaging in regular physical activity as tolerated, maintaining a healthy weight and quitting smoking can all improve vascular health.

Assistive devices for erectile dysfunction

For men with ED that is refractory to medication, mechanical aids are an important and effective option. Vacuum constriction devices consist of a plastic cylinder placed over the penis, a hand-held pump that creates a vacuum to draw blood into the penis, and a constriction band that is slipped onto the base of the penis to trap the blood and maintain the erection for up to 30 minutes.

Vacuum constriction device operated by a hand-held pump.

Penile prostheses or penile implants are a surgical solution for severe, intractable ED. A device is surgically implanted into the penis that allows the man to create a rigid erection mechanically. This uses saline to inflate the cylinder that is implanted in the penis. The saline can be pumped from a reservoir into the prosthesis or erectile cylinder to mimic an erection. The saline can then be pumped from the cylinder back into the reservoir to cause detumescence. This is typically considered a third-line treatment when all other options have failed.

Penile implant for severe erectile dysfunction

Education, education, education ….

Providing clear, accurate information to the patient and their partner about how MS can affect sexual function helps to demystify the problem, correct common misconceptions (e.g. that sexual activity will worsen the disease), and empower the couple to explore solutions collaboratively.

A management plan for male sexual dysfunction needs to be personalised to address specific primary, secondary and tertiary factors. The goal is often not just to restore previous sexual function but to help the man with MS to adapt to a new reality, encouraging him and his partner to build a new, satisfying form of intimacy.

This calls for improved clinical education of MS healthcare professionals, the integration of standardised screening tools into routine care, and a fundamental shift in clinical culture toward a more holistic model of well-being that values sexual health as a core component of MS management.

Fatigue and insomnia, Sleep disorders

Understanding and managing insomnia in MS

Insomnia is the most common sleep disorder I encounter in my MS practice. It often goes untreated because people with MS accept it as part of living with the disease or because healthcare professionals (HCPs) prioritise other MS-related problems.

Key points

  • Insomnia is more common in people with MS than in the general population and is associated with poor mental health and other medical problems.
  • Factors that contribute to insomnia include anxiety, frequent visits to the bathroom, pain, leg spasms, restless legs, inability to roll over in bed, menopausal symptoms (hot flushes and night sweats) and poor sleep hygiene; they need to be managed appropriately.
  • Several online tools and questionnaires exist that can help you assess the nature and severity of insomnia.
  • Sleep aids (drugs) available over the counter or on prescription may be helpful.
  • Cognitive and digital approaches to insomnia management also have a role but are not widely available or suitable for everyone.
  • Complementary and alternative therapies are a valuable aid to self-management of insomnia.

Sleep, glorious sleep!

Sleep is the most essential performance-enhancing agent we know. You know what it is like if you wake in the morning and have had a good night’s sleep; you feel energised, your mood is good and you are ready to face the day. In contrast, when you wake from a night of tossing and turning, or not being able to turn, legs jerking, getting up several times to go to the toilet, maybe with a hangover from too much alcohol the night before, then you are irritable, your mood is low and it is challenging to get through the day. 

Most studies on sleep in MS show that over 70% of people with MS have a sleep disorder. In an MS-Selfie survey on sleep, a minority (33%) of 173 respondents described their sleep as good, very good or excellent, with 49% formally diagnosed with one or more sleep disorder and over 80% not having undergone formal sleep studies. Insomnia is the most common sleep disorder I encounter in my MS practice. Insomnia is defined as difficulty initiating or maintaining sleep, which can be a symptom or a disorder. If a disorder, insomnia is associated with a feeling of distress about poor sleep, and it disrupts social or occupational functioning.

Causes and impact of insomnia

In the general population, ~10% of adults have insomnia disorder and another 15 ̶ 20% report occasional insomnia, i.e. the symptom. In comparison, 40 ̶ 50% of people with MS have insomnia. Insomnia is more common in women than in men and is associated with poor mental health and other medical problems. Common MS-associated symptoms linked to insomnia (and resulting in fatigue) include pain, lack of bladder control, spasticity, restless legs, periodic limb movements and discomfort from being unable to turn in bed; other factors that contribute to insomnia – not just in people with MS but also more widely –  include alcohol and stimulant misuse, menopausal symptoms, poor sleep hygiene (daytime napping), deconditioning (lack of exercise), anxiety and depression. All these problems can interfere with sleep initiation, maintenance or perception in people with MS.

Insomnia can be episodic (with symptoms lasting 1 ̶ 3 months) or situational (of short duration, in response to a specific event of circumstance) and tends to follow a persistent course. Episodic insomnia refers to insomnia for a defined period, for example lasting several months linked to anxiety. In comparison, situational insomnia refers to insomnia triggered by a specific stimulus or event, such as sleeping away from home or after alcohol consumption. Chronic insomnia can cause depression and is associated in the general population with the development of hypertension and dementia. Insomnia assessment, diagnosis and management require a careful history to document its course, concomitant comorbidities and potential contributing factors. 

Several studies show that approximately 40% of people with MS have obstructive sleep apnoea and that it is not necessarily associated with obesity and a large neck. Sleep apnoea in MS may be due to brain stem pathology from MS affecting pharyngeal (throat) muscle function. If you know or think you are a snorer and you have periods when you stop breathing, you can download one of the many smartphone sleep apps that can assess this.

Approaches to managing insomnia

Any MS-related symptoms that can affect sleep need to be managed appropriately. How can you treat insomnia if your sleep is interrupted by anxiety-related rumination, nocturia, pain, leg spasms, restless legs, inability to roll over in bed, menopausal symptoms of hot flushes and night sweats and poor sleep hygiene? 

Recording your sleep patterns

A 24-hour history of sleep ̶ wake behaviours can help to identify additional behavioural and environmental factors for intervention. Patient-reported outcome measures (PROMS) and sleep diaries provide valuable information about the nature and severity of insomnia. They can help screen for other sleep disorders and monitor treatment progress.

A sleep diary should collect information on your sleep cycle (bedtime, arising time, napping) and estimates of your sleep ̶ wake characteristics, i.e. sleep latency (how long it takes to fall asleep), number and duration of awakenings, and an estimated overall sleep time. Useful PROMS include the Insomnia Severity Index, the Pittsburgh Sleep Quality Index, the STOP-BANG Sleep Apnea Questionnaire (for evaluating the risk of sleep apnoea) and the Restless Legs Syndrome Rating Scale. 

Sleep hygiene

I suggest you start with a simple self-help guide to improve your sleep hygiene.

  1. Ensure you spend an appropriate amount of time asleep, at least 6 hours in bed. Some people need more than this to feel refreshed. 
  2. Limit daytime naps to 30 minutes. Please note that napping does not make up for inadequate nighttime sleep. 
  3. Avoid stimulants such as caffeine, modafinil and nicotine close to bedtime. 
  4. Only drink alcohol in moderation. Alcohol is known to help you fall asleep faster, but too much disrupts sleep.
  5. Exercise helps improve sleep quality. As little as 10 minutes of aerobic exercise daily can enhance the quality of sleep. 
  6. Don’t eat before going to bed. Heavy foods and fizzy drinks can trigger indigestion or heartburn/reflux that disrupts sleep.
  7. Ensure you get adequate exposure to natural light; exposure to sunlight during the day and darkness at night help to maintain a regular sleep ̶ wake cycle. 
  8. Establish a regular relaxing bedtime routine, which helps the body recognise it is bedtime. This could include taking a shower or bath or reading. However, avoid reading or watching emotionally upsetting content before attempting to sleep.
  9. Make sure that your sleep environment is pleasant. Your mattress and pillows should be comfortable. The bedroom should be cool for optimal sleep (16 ̶ 20°C). The bright light from lamps, smartphones and television screens can make it difficult to fall asleep, so turn those lights off or adjust them when possible. Use the blue filter mode on your smartphone and other devices to reduce the inhibition of melatonin from light. Consider using blackout curtains, eyeshades, earplugs, white noise machines and other devices to make the bedroom more relaxing.
  10. If you have pain, nocturia, restless legs, sleep apnoea or other causes of discomfort, get these adequately managed via your HCP.

If these self-help measures fail, other current treatment options include prescription-only and over-the-counter (OTC) medications, cognitive behavioural therapy for insomnia (CBTI) and complementary and alternative therapies. 

Over-the-counter sleep aids

Over-the-counter sedatives tend to be first-generation antihistamines with potent centrally acting anticholinergic effects that impair cognitive function and long-term brain health. I recommend you avoid them (see newsletter entitled ‘Your anticholinergic burden’). 

Some people with MS self-medicate with OTC melatonin, cannabidiol (CBD) or tetrahydrocannabinol (THC) preparations. Melatonin has a U-shaped dose ̶ response curve for some individuals; therefore, lower doses may be better than higher doses. In general, I cannot recommend the use of CBD or THC for insomnia. CBD is a drug and is associated with liver toxicity; it may also interact with your other medications. However, if you do decide to buy CBD and/or THC, please use a reputable supplier and pharmaceutical-grade products. Medicinal cannabis cannot be prescribed on the NHS but can be obtained via private clinics. Many patients purchase it online; as a doctor, I cannot recommend buying it this way. 

Prescription-only sleep aids

If you raise the issue of insomnia with your HCP, they may reach for the prescription pad. Before accepting a sedative, please be aware of its limitations and ensure you have optimised all the above guidance. Sedatives are only a short-term solution; they work well for about 4 ̶ 5 days before you develop tachyphylaxis and need higher doses. Tachyphylaxis refers to the rapidly diminishing response to successive doses of a drug, rendering it less and less effective. Once you develop tachyphylaxis and stop taking sedatives, you may experience rebound insomnia. Benzodiazepines (e.g. diazepam) are addictive and doctors generally avoid prescribing them for insomnia. However, they still have a role when insomnia is part of acute anxiety. The sedatives most often used are the so-called Z-drugs (zolpidem, zopiclone, zaleplon and eszopiclone). Zopiclone and eszopiclone have a longer half-life than the other two drugs (5 ̶ 6 hours). In comparison, zolpidem and zaleplon act for a much shorter period (1 ̶ 3 hours). 

The older, tricyclic antidepressants, such as amitriptyline, are commonly used as sedatives. I have largely stopped prescribing them unless there is another reason for using a tricyclic, e.g. to help with pain management (please read my newsletter ‘Amitriptyline: the neurologist‘s dirty little secret’. I mostly use duloxetine in my clinical practice for pain management. It is not as sedating as tricyclic antidepressants, but some patients find it helps with sleep. Duloxetine is a serotonin ̶ noradrenaline reuptake inhibitor and has fewer anticholinergic side effects than tricyclics.

Antispasticity agents such as baclofen and gabapentinoids (gabapentin and pregabalin) also help sleep, but they should only be used for insomnia if you have spasticity or, in the case of the gabapentinoids, spasticity and/or pain that needs to be managed.  

Psychiatrists and some neurologists use sedating antipsychotics to help with insomnia. Sadly, as a neurologist, I have seen too many severe adverse events resulting from the liberal use of antipsychotics as sedatives. There needs to be a good reason for prescribing an antipsychotic, and insomnia in isolation is not one of them; however, there is a role for them in patients with cognitive issues or significant psychiatric problems. The older generation antipsychotics (e.g. haloperidol) have now been replaced by safer drugs such as quetiapine and olanzapine.

A new class of sedatives is now available in some countries; these are the dual orexin receptor antagonists suvorexant, lemborexant and daridorexant. Daridorexant is NICE approved for use by the NHS; it is recommended for treating insomnia in adults with symptoms lasting for 3 nights or more per week for at least 3 months and whose daytime functioning is considerably affected, but only if CBTI has been tried and not worked, or if CBTI is not available or is unsuitable.

Cognitive approaches to managing insomnia

Cognitive Behavioural Therapy for Insomnia (CBTI)

Only some patients receive CBTI, owing to a lack of adequately trained therapists. CBTI aims to change the behaviour and psychological factors that contribute to insomnia (e.g. anxieties and unhelpful beliefs about sleep). At the core of CBTI are behavioural and sleep-scheduling strategies (sleep restriction and stimulus control instructions), relaxation methods, psychological and/or cognitive interventions to change unhelpful beliefs or excessive worrying about insomnia, and sleep hygiene education. 

CBTI is focused on sleep and oriented toward problem-solving. A psychologist typically guides the process over roughly six consultations. Several variants in the methods for implementing CBTI include shorter formats, group therapy, using other providers such as counsellors and specialist nurses, and the use of telehealth digital platforms, including smartphone applications. 

Brief behavioural treatment for insomnia

This abbreviated version of CBTI emphasises behavioural components and is typically implemented in fewer sessions. It involves education about sleep regulation, factors that promote or interfere with sleep, and a tailored behavioural prescription based on stimulus control and sleep restriction therapy.

eCBTI

Digital CBTI (eCBTI) is becoming increasingly popular. The Sleepio application, which is recommended and covered by the NHS, has a positive effect on several sleep outcomes and is said to be as effective as medication. NICE recommends Sleepio as a cost-saving option for treating insomnia and insomnia symptoms in primary care for people who would otherwise be offered sleep hygiene or sleeping pills. A medical assessment should be done before referral to Sleepio for people who may be at higher risk of other sleep disorder conditions, such as during pregnancy or in people with comorbidities.

Complementary and alternative therapies

Sleep restriction

Limit the time you spend in bed to match your sleep time as closely as possible. After the initial restriction, the sleep window can be gradually adjusted upward or downward on a weekly basis as a function of sleep efficiency (time asleep÷time spent in bed×100) until an appropriate sleep duration is established.

Stimulus control

You need to follow a set of instructions designed to reinforce the association between bedtime and bedroom stimuli with sleep and to re-establish a consistent sleep ̶ wake schedule.

  • Go to bed only when you feel sleepy.
  • Get out of bed when you are unable to sleep.
  • Use the bed and bedroom for sleep and sex only; do not use your bed for reading, watching television, etc.
  • Try and get up at the same time every morning.
  • Avoid napping.

Relaxation training

Try using different procedures such as progressive muscle relaxation and imagery training to reduce arousal, muscle tension and intrusive thoughts that interfere with sleep. Relaxation procedures need to be practised daily over a few weeks. 

Cognitive therapy

This is a psychological approach to revising many common misconceptions about sleep and reframing unhelpful beliefs about insomnia and its daytime consequences. This method also reduces excessive worrying about sleep difficulties and their daytime consequences. Additional cognitive strategies include paradoxical intention (willingly trying to stay awake rather than trying to fall asleep) to alleviate the performance anxiety triggered by attempting to force sleep.

Sleep hygiene education

These general guidelines include advice about a healthy diet, exercise, substance use, and optimising environmental factors such as light level, noise and excessive temperature that may promote or interfere with sleep (see above). 

Acceptance and commitment therapy (ACT)

ACT is a form of psychotherapy that aims to educate people to stay focused on the present moment and accept life experiences, thoughts, and feelings (even negative ones) without trying to change them. ACT uses different methods and processes (e.g. acceptance, defusion, mindfulness, and committed action) to increase psychological flexibility.

Mindfulness

This meditation method involves observing one’s thoughts and feelings and letting go of the need to change or ruminate. Originally designed to reduce stress and anxiety, mindfulness has been adapted for the management of insomnia and can be included as one component of ACT.

Conclusion

Poor sleep, be it due to a comorbid sleep disorder, MS-related symptoms or poor sleep hygiene, is a very common problem in people with MS. It contributes to daytime fatigue and hypersomnolence and impacts physical and cognitive function. As a result, poor sleep reduces quality of life and can exacerbate other MS-related problems such as poor cognition, anxiety and depression. It is essential that poor sleep is documented, investigated appropriately and treated accordingly to improve the functioning and quality of life of people with MS.

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.