All posts by Gavin Giovannoni

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.

Bladder and bowel, Intimate issues

Intimate issues: bladder dysfunction

Bladder dysfunction in people with MS is a sign of early damage, particularly to the spinal cord, and an early indication of a poor prognosis. Why do people with MS who develop bladder dysfunction do worse than those with no bladder symptoms? Here, I explain why I take bladder problems seriously and their implications for MS management.

Key points

  • Urinary hesitancy, urgency, frequency and incontinence, including at night, are bladder problems that affect many people with MS and cause significant frustration and anxiety.
  • A range of drug-based treatments, behavioural techniques and specialist physical interventions can help people with MS to manage bladder dysfunction and achieve adequate control.
  • However, the bladder pathways will probably continue to be affected in the long term due to the development of new lesions or the expansion of old lesions.
  • Frequent and severe urinary tract infections (UTIs) increase the likelihood that MS will progress.
  • I recommend regular dipstick testing at home, as part of your MS self-management, to increase the chances of early detection and treatment of a UTI.
  • Lifestyle approaches, such as avoiding smoking and reducing alcohol and caffeine consumption, should help to reduce bladder symptoms. Pelvic floor exercises are also important.
  • Dehydration is not a good way to control your bladder symptoms. Chronic dehydration can have a significant impact on your overall health and well-being and can exacerbate many of your MS symptoms.

Causes and significance of bladder dysfunction

Bladder dysfunction is the most common symptomatic problem I encounter in an MS clinic, affecting more than 50% of people with MS. It is one of the signs of early damage, particularly spinal cord damage, and an early indication of a poor prognosis. It therefore has important implications for treatment: if you have early bladder symptoms, you may want to take a more effective therapy early on rather than starting on a less effective DMT and waiting to see how you respond. It is best to maximise your chances of responding to treatment by opting for a highly efficacious therapy first-line. I call this ‘flipping the pyramid’.

Infections, both viral and bacterial, are a known trigger of relapse in MS. Frequent and severe urinary tract infections (UTIs) increase the likelihood that your MS will progress. This is why it is important to improve the management of bladder problems in people with MS to prevent or reduce UTIs. You can read more about managing  UTIs here.

Why do people with MS who develop bladder dysfunction do worse than those with no bladder symptoms? The bladder is a complicated organ with several neurological components that need to be coordinated. The descending nerve fibres that travel from the brain to the lower segments of the spinal cord are very long and have the greatest chance of being damaged by MS lesions in their path down to the bladder centre in the sacral area of the lower spinal cord. Therefore, any progressive or worsening MS damage is likely to manifest with bladder dysfunction early on.

The detrusor (or balloon) muscles and the sphincter (or valve) need to coordinate their action to enable normal bladder function. When the bladder is filling, the detrusor muscle relaxes to allow the bladder to expand and the sphincter contracts to keep the urine in the bladder. The opposite occurs when you pass urine; the sphincter opens and the detrusor contracts to empty the bladder.

Common MS-related bladder problems

Hesitancy

Urinary hesitancy occurs when the function of the detrusor and sphincter muscles is not coordinated: you try to pass urine, but the bladder sphincter won’t open. Hesitancy may be intermittent; if you try again later, the bladder will open, allowing you to pass urine. Conversely, the sphincter may close as you pass urine, which breaks up the urine stream or prevents complete bladder emptying; this can cause dribbling. The medical term for incoordination of the bladder muscles is dyssynergia or, more correctly, detrusor-sphincter-dyssynergia (DSD). People with MS find urinary hesitancy and its unpredictability very frustrating.

The drug treatment for DSD includes alpha-blockers (prazosin, indoramin, tamsulosin, alfuzosin, doxazosin and terazosin). Other strategies include small bladder stimulators or vibrators that are placed over the pubic area and work by blocking signals that inhibit the sphincters. The vibrators work in some people with MS and may help relax the sphincter.

Trying to relax when passing urine can help to improve hesitancy. The sound of running water, for example from a tap, may trigger the relaxation of the sphincter. Simulating this in public toilets may not be possible. Some people with MS find pressing on the lower abdomen helps. If all else fails, intermittent self-catheterisation (ISC) may be the only option to manage urinary hesitancy (see below).

Frequency and urgency

In MS the commonest bladder problem is spasticity, or irritability, of the detrusor muscle. The detrusor can’t relax, which prevents the bladder from filling to its maximum capacity. Frequent spasms of the detrusor muscle tell the brain that the bladder is full and you need to pass urine. This causes frequency, i.e. the need to use the toilet many times during the day and night. Frequency often accompanies the symptom of urgency, the need to get to the toilet as quickly as possible to prevent incontinence. 

When urgency is a problem, distraction techniques such as breathing exercises and mental tricks (e.g. counting) may be helpful. If urinary frequency is your main problem, you might try to retrain your bladder by holding on for as long as you can each time before passing urine. The aim is to train the detrusor muscle to expand more to hold on for longer when you need the toilet. These behavioural techniques rarely work for long; MS is a relapsing and/or progressive disease, and the bladder pathways will likely continue to be affected due to the development of new lesions or the expansion of old lesions.

Incontinence

Incontinence occurs when you lose the ability to suppress or ignore the signals from the detrusor muscle with the result that the sphincter relaxes or opens as part of a spinal cord reflex. We typically treat this problem with anticholinergic drugs, e.g. oxybutynin, solifenacin or tolterodine. The older generation anticholinergics such as oxybutynin cross the blood ̶ brain barrier and enter the brain, where they can exacerbate cognitive problems in people with MS. The commonest side effect of anticholinergics is dryness of the mouth; they can also worsen constipation. People with MS must be warned about the risk that anticholinergics will relax the bladder too much and precipitate urinary retention; the solution to urinary retention is ISC. 

The good news is that we now have a relatively new muscle relaxant, mirabegron (Betmiga), which activates the β3 adrenergic receptor in the detrusor muscle. I am increasingly using mirabegron to avoid the side effects (particularly cognitive issues) associated with anticholinergics. The main side effect of mirabegron is that it tends to increase your blood pressure.

Nocturia

Nocturia means you need to get up frequently at night to pass urine. If nocturia is your main bladder problem, using agents to concentrate the urine at night might help. A hormone called DDAVP works on the kidneys to reduce urine production; it is available as a nasal spray or tablets (Desmotabs or Desmospray). DDAVP should only be taken once a day, to avoid continuous water retention by the kidneys; this presents as swelling of the feet and reduces the salt or sodium levels in your blood, which can be dangerous. You therefore need to have your sodium levels checked about 4 ̶ 6 weeks after starting DDAVP therapy. 

Second-line treatments for bladder problems

If you fail to respond to anticholinergics, mirabegron and/or behavioural techniques, you need a bladder scan to see if you have a raised residual volume (the amount of urine left after you have emptied your bladder). If the residual volume is greater than 80 ̶ 100mL you may need to consider intermittent self-catheterisation (ISC). Some continence advisors act at the 80 mL threshold, and others at the 100 mL threshold, when recommending ISC.

Intermittent self-catheterisation

ISC serves two purposes. It increases your functional residual bladder volume, allowing more storage space for urine, which reduces frequency and urgency. This can help if you need to travel some distance or to join in a social activity without having to pass urine. It also helps to reduce nocturia, which in turn improves sleep and possibly MS-related daytime fatigue.

ISC also removes urine from the bladder. The residual urine acts as a culture medium for bacteria; by clearing your bladder you can prevent bladder infections. Conversely, if you don’t do the ISC technique correctly you can introduce bacteria into the bladder that then cause infections.

Botox

Botox injection into the detrusor muscle is increasingly used as a treatment for bladder dysfunction, in conjunction with ISC. Botox paralyses the muscle, turning it into a flaccid bag for urine storage. The surgical techniques that were previously used to remove the nerve supply to the bladder (which had the same effect as Botox) are now rarely used.

Percutaneous tibial nerve stimulation 

Percutaneous (or posterior) tibial nerve stimulation is a form of neuromodulation that can help with impaired bladder function and may improve urinary urgency, urinary frequency and urge incontinence. It is offered as a treatment in specialist neuro-urology units.

Permanent catheterisation

If all else fails, some people with MS may need to be permanently catheterised. This can be done via the urethra or the lower abdominal wall; the latter is called a suprapubic catheter. Being permanently catheterised sounds drastic, but this significantly improves the quality of life in some people with MS. Allowing bladder dysfunction to control your life can result in social isolation and constant anxiety about being incontinent in public. With the above-mentioned strategies, adequate bladder control should be the norm in MS.

In my experience, the biggest hurdle to achieving adequate bladder control is when people with MS assume their bladder symptoms are part of the disease and resign themselves to living with them. Such patients may start using continence pads as if this is normal or inevitable for someone living with MS. This is not normal; incontinence can lead to skin rashes and pressure sores. Please don’t accept this as the norm or something you must live with. If you have problems, tell your MS nurse or neurologist; they can help you.

Anatomy of the human urinary bladder; reproduced from Wikipedia, created by U.S. National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Program.

Lifestyle factors that impact your bladder

Smoking, alcohol and caffeine

Nicotine irritates the bladder. If you are a smoker, then stopping smoking may significantly improve your bladder symptoms. Similarly, reducing alcohol and caffeine consumption may help; these agents are diuretics and cause the kidneys to make more urine.

Pelvic floor exercises

One of the treatments recommended to all patients with bladder problems is pelvic floor exercises. These are also important for managing bowel and/or sexual problems. For detailed guidance on incorporating these into your daily life, please see pelvic floor training post.

Avoiding dehydration

Try to anticipate times when urinary frequency and urgency will be most inconvenient; reducing the amount you drink beforehand may help. For example, don’t drink too much for 2 ̶ 3 hours before you go out. After you have finished passing urine, go back to the toilet again after a few minutes to try to pass some more urine. This is called the double micturition technique, which aims to ensure the bladder is emptied completely. However, do not reduce your total fluid intake to less than 1.5 litres each day.

Dehydration is not a good way to control your bladder symptoms. The issue of people with MS dehydrating themselves to manage their bladder problems was highlighted as early as the 1960s by Professor Bryan Matthews, a neurologist in Oxford, in his textbook on MS.

When researching the topic in the 1990s, it became clear to me that people with MS with severe disability were most likely to have bladder dysfunction and were chronically dehydrating themselves to manage urinary frequency, urgency and nocturia. Studies showed that a high urinary concentration of creatinine, a waste product that the kidneys filter out of the blood through the urine, correlated with increased disability levels. Urine containing myelin basic protein-like material (MBPLM), an indicator of myelin damage in MS, was also shown to correlate with disability. It is dehydration that causes higher levels of MBPLM and creatinine in the urine, indicating that dehydration is associated with disability.1 

A more recent paper from researchers in the Southampton group described the same findings, that urinary tract symptoms are very common in people with progressive MS and are associated with inadequate hydration.2

Despite highlighting the issue of chronic dehydration in MS over the years, it remains a persistent problem. My message is clear: don’t use dehydration to manage your bladder symptoms. Chronic dehydration can have a significant impact on your overall health and well-being and can exacerbate many of your MS symptoms. Some potential effects of chronic dehydration are listed in the box below.

  1. Physical performance: Dehydration can decrease physical endurance, cause muscle cramps and exacerbate or cause fatigue. This can affect overall physical performance and make everyday tasks more challenging.
  2. Cognitive function: Dehydration has been linked to cognitive impairment, including issues with concentration, alertness and short-term memory. Prolonged dehydration may even contribute to long-term cognitive decline.
  3. Mood and mental health: Studies have shown that dehydration can affect mood and contribute to increased feelings of anxiety and irritability. In severe cases, it can even lead to symptoms resembling depression.
  4. Kidney function: Chronic dehydration can put a strain on the kidneys, potentially leading to the formation of kidney stones and urinary tract infections. It can impair the kidneys’ ability to effectively filter waste from the blood. It also makes you more susceptible to the side effects of non-steroidal anti-inflammatory medications.
  5. Digestive problems: Dehydration can lead to constipation and other digestive issues. It may also contribute to an increased risk of developing peptic ulcers and acid reflux.
  6. Skin health: Inadequate hydration can lead to dry, flaky skin and exacerbate conditions such as eczema and psoriasis. Proper hydration is essential for maintaining overall skin health and elasticity.
  7. Heat-related illnesses: Dehydration reduces your body’s ability to regulate temperature, increasing the risk of heat exhaustion and heat stroke, particularly in hot and humid conditions. Please remember that people with MS, particularly those with more advanced MS, may already have a problem with thermoregulation.

In conclusion

I advise using a holistic approach to managing urinary symptoms, in addition to medication or other aids where recommended. Please review the questions below to check whether you are optimising your self-management.

  • Have you deconditioned your bladder because you are not training yourself to resist emptying it whenever you get the urge to pass urine? The bladder is a muscle that needs to be trained.
  • Have you tried peripherally acting anticholinergics or mirabegron?
  • Have you had a post-micturition bladder scan to see if you are emptying your bladder?
  • Do you need to use intermittent self-catheterisation to increase your functional bladder volume?
  • Do you have a chronic low-grade urinary tract infection? Are you performing regular urine dipstick testing (see post on UTIs and dipstick testing)?
  • Do you have bladder stones?
  • Have you tried DDAVP (Desmotabs or Desmospray) to help concentrate your urine without dehydrating yourself?
  • Are you avoiding bladder irritants or stimulants such as caffeine and nicotine?
  • Are you doing your pelvic floor exercises? If you are a post-menopausal woman, have you tried HRT (hormone replacement therapy)? Pelvic floor tone and bladder function often improve on HRT. 

References

  1. Giovannoni G, et al. Urinary myelin basic protein-like material as a correlate of the progression of multiple sclerosis. Ann Neurol 1996;40:128 ̶ 9.
  2. Kaninia S, et al. Dehydration associates with lower urinary tract symptoms in progressive multiple sclerosis. Eur J Neurol 2024;31: e16175.
Bladder and bowel, Intimate issues

Detecting and preventing urinary tract infections

Frequent and severe urinary tract infections (UTIs) increase the likelihood that MS will progress. I recommend regular dipstick testing at home, as part of your MS self-management, to increase the chances of early detection and treatment of a UTI.

Urinary tract infection and disease progression

Infections, both viral and bacterial, are a known trigger of relapse. Frequent and severe urinary tract infections (UTIs) increase the likelihood that your MS will progress. This is why it is important to improve the management of bladder problems in people with MS to prevent or reduce urinary tract infections. You can do this in several ways, such as increasing the frequency of ISC.

Drinking plenty of liquids to flush the bladder reduces infection rates. Changing the pH of your urine by drinking citric acid (citro soda or lemonade) also helps. Making your urine more alkaline or more acidic may work, depending on the bacterial species colonising your bladder. Cranberry extract, for example, contains proanthocyanidins, a substance that reduces bacterial colonisation of the bladder. (You need to use the extract and not the juice because the proanthocyanidin concentration in the juice is too low to have an effect.)

Another very effective option (but infrequently used) is a bladder instillation with a liquid containing sodium hyaluronate (Cystistat), which replaces the glycosaminoglycan layer, or glycocalyx, of the bladder wall. This makes it difficult for bacteria to stick to the bladder wall to cause infections and is one way of preventing bacterial biofilms, or slime, from forming. Biofilms are a significant problem because they prevent antibiotics from reaching the bacteria to kill them and act as a breeding place for recurrent infections.

Urinary antiseptics are antibiotics, given in low concentrations, that may help to reduce urinary tract infection rates. They are typically administered in tablet form; they work by being concentrated by the kidneys and making the urine antiseptic, which helps to prevent or treat urinary tract infections. The agents I use currently are trimethoprim, cephalexin and nitrofurantoin. (Methenamine, another urinary antiseptic, is not readily available in the UK due to supply issues.) Cycling their use, every 3 ̶ 4 months, prevents the bladder bacteria from becoming resistant to a specific antibacterial. We have stopped using nalidixic acid and other drugs in the oxolinic acid class because they are associated with tendonitis and tendon ruptures.

Interpretation of urine dipstick results

Early detection of urinary tract infections (UTIs) means that they can be treated promptly to prevent symptomatic infection or complications such as pyelonephritis (kidney infection) and septicaemia (a common cause of death in people with advanced MS). Dipstick testing can be carried out at home, as part of self-management of your MS. I recommend doing dipstick monitoring once or twice a week, not daily. If positive, you must drop off a clean urine sample to your healthcare provider for proper laboratory analysis (microscopy, culture and sensitivity). This is to confirm the presence of a UTI, to culture and isolate the bacteria causing the infection, and to test the sensitivity of the bacteria to antibiotics. You must send your urine specimen for analysis before you start antibiotics. 

For UTI monitoring, the leukocyte and nitrite tests are the most important, with backup from the protein, blood and pH tests. The guidance in the table below explains how to interpret some of the key dipstick test results relevant to UTIs and what the different readings on a typical urine dipstick mean. You need to wait up to 2 minutes to read the results; if in doubt, take a picture of the test strip with your mobile phone and email it to your HCP for interpretation.

Dipstick results

Guidance to help you interpret the dipstick results relevant to urinary tract infection (UTI). You should wait for up to 2 minutes before reading the results (2 minutes for leukocytes, at least 60 seconds for other results shown here).
*If you have been treated with alemtuzumab, new-onset proteinuria in the presence of blood may indicate Goodpasture’s syndrome, a rare autoimmune complication of alemtuzumab treatment. Please consult your HCP.
UTI, urinary tract infection.

The image below shows what the different readings on a typical urine dipstick mean; the readings for white blood cells, nitrite, protein, pH and blood are important for detecting the presence of a UTI (more information is in the Table above). Further details about readings for urobilinogen,  specific gravity, ketone levels, bilirubin and glucose are available in my newsletter entitled How to interpret a urine dipstick result.

An example of results from a urine dipstick test; the readings most relevant to interpreting urinary tract infections are white blood cells, nitrite, protein, pH and blood. Information about additional results from dipstick testing are available in my newsletter entitled How to interpret a urine dipstick result.

Bladder and bowel, Intimate issues

Intimate issues: bowel disorders

Here I discuss why people with MS develop problems with their bowel function and I offer straightforward advice on how to manage constipation, diarrhoea and other MS-related bowel problems.

Key points

  • Many people with MS experience a bowel disorder as a result of changes within the central nervous system that may affect the rectal and anal muscles.
  • Agents that increase the muscular action of the bowel can help to treat constipation.
  • Medications for some MS symptoms can increase constipation and may need to be reviewed.
  • Faecal impaction associated with constipation is a serious problem that may need hospital treatment.
  • Small intestinal bacterial overgrowth (SIBO) from faecal impaction may occur if the bacteria of the small intestine increase above normal values, producing harmful toxins.
  • SIBO is associated with unpleasant symptoms including abdominal bloating, pain, anaemia, irritable bowel syndrome, constipation, diarrhoea and faecal impaction.
  • Bowel hypomobility and any faecal impaction underlying SIBO need to be addressed, and antibiotics may be required to reduce the abnormal bacteria in the bowel. A gut health programme and dietary review are important for long-term management.
  • Being incontinent of faeces in public is highly embarrassing and may lead to severe anxiety and social isolation.
  • Faecal urgency or incontinence are best treated by developing a bowel routine and trying to evacuate your bowels in a controlled environment and at a regular time of day.
  • Regular rectal or transanal irrigation can significantly improve the quality of life in such cases.
  • MS should be treated early with effective DMTs, to avoid or delay damage to the neuronal pathways that control bowel function.

Many people with MS experience bowel disorders, including constipation, faecal hesitancy (difficult initiating a bowel action), incomplete emptying, faecal urgency, urgency incontinence, overflow diarrhoea, excessive bloating and excessive flatus. Understanding the causes of rectal and anal dysfunction in patients with MS can help us to select the most relevant therapies to target specific symptoms.

People with MS who experience constipation generally have a loss of sphincter tone (strength) at rest and during contraction compared with non-MS patients. In faecal incontinence, rectal sensitivity threshold is reduced, meaning that when faeces enter the rectum the threshold at which the defaecation reflex is triggered is lower than normal. There is also evidence that the coordination of the pelvic floor following contraction of the anal sphincter is abnormal in people MS. Pelvic floor exercises may help with this.

Management of constipation

Bowel dysfunction, particularly constipation, is common in MS. Constipation occurs because the MS bowel is sluggish due to reduced motility (i.e. the muscles or nerves do not work as they should). The management aim is usually to encourage regular bowel action, either daily or at least every two days.

Prokinetic agents that increase the muscular action of the bowel can help to treat constipation. The prokinetic agent I prescribe most often is senna. If this fails, other options include bisacodyl, co-danthrusate, sodium picosulfate or prucalopride; these agents work by stimulating the nervous system in the bowels. Prokinetic agents often need to be taken with bulking (fibre) and loosening (liquid) agents. Bulking agents include methylcellulose, psyllium or ispaghula husks, and sterculia granules. Loosening agents keep liquid in the bowel, causing water to be retained with the stool; examples include lactulose, polyethylene glycol (Movicol), magnesium hydroxide and magnesium sulphate (Epsom salts).

Cyclical use of laxatives can contribute to ongoing constipation: you use laxatives to treat your constipation, the laxatives cause diarrhoea, so you stop taking them. You then become constipated again, and the cycle repeats itself. 

If you experience bladder incontinence, dehydrating yourself to control your bladder problems can make constipation worse; you must drink adequate quantities of water throughout the day. Similarly, anticholinergic drugs used for treating urinary frequency and urgency and treatments for pain and spasticity may all make constipation worse. Therefore, if you are constipated your medications for other symptoms of MS need to be reviewed. 

Faecal impaction

Over time, the bowels may become impacted with faeces, and a hard, stony mass of compacted faeces forms (known as a faecolith). The gut bacteria may then overgrow and liquefy the stool above this impacted faecolith, bypass the impaction and cause diarrhoea. A typical history of faecal impaction includes periods of constipation punctuated by episodes of diarrhoea. If you suffer from chronic constipation and intermittent diarrhoea, you should contact your health team for help. Faecal impaction is a serious problem and often warrants treatment in hospital.

Below are some tips for managing MS-related constipation.

  1. Optimise your diet by eating lots of fibre.
  2. Don’t dehydrate yourself. Drink plenty of water; be aware that caffeine and alcoholic beverages are not hydrating. Both cause the kidneys to make more urine (diuresis) and are dehydrating.
  3. Try to eliminate the concurrent use of medications that exacerbate constipation (anticholinergics and opioids).
  4. Exercise regularly; the anticipation of exercise and exercise itself stimulate a defaecation reflex.
  5. If you need to use laxatives, start with a prokinetic agent that stimulates the bowel to move, such as senna; then add in bulking agents (e.g. psyllium husks or other fibre substitutes) followed by liquifying agents (lactulose or polyethylene glycol).
  6. Don’t suppress the need to go to the toilet; many people with chronic constipation have learnt bad habits (such as not using toilets that are unfamiliar to them).
  7. Try to develop a daily bowel routine, for example, by having a bowel movement at a particular time (ideally in the morning). This may require you to stimulate a bowel movement, perhaps by eating something, drinking a caffeine-containing drink, anal stimulation (anal plug), using glycerine suppositories, mini-enemas or (if necessary) an anal irrigation system. An anal plug is used to stimulate the colonic emptying reflex and is removed before you have bowel action.

These final recommendations may sound extreme, but they are essential steps to prevent faecal impaction. They may also give you the confidence to go out knowing that you can avoid faecal urgency and incontinence.

Small intestinal bacterial overgrowth (SIBO)

People with MS with bowel dysfunction may develop small intestinal bacterial overgrowth (SIBO), which is defined as an increase in the bacterial content of the small intestine above normal values. Some studies show that four in every 10 people with MS have SIBO; it is also detected in approximately one-third of patients with gastroenterological complaints who undergo a breath test. Proton pump inhibitors (omeprazole and related drugs) and smoking are risk factors for developing SIBO. The risk of SIBO increases with age and does not depend on gender or race.

SIBO is associated with dyspepsia, abdominal bloating, abdominal pain, anaemia, irritable bowel syndrome, functional constipation, diarrhoea and faecal impaction. A slowdown in your bowel transit time with SIBO decreases the normal clearance of bacteria from the small intestine. This slowdown is due to changes in the motility of the intestine, which is almost universal in people with MS.

Risks from SIBO

SIBO may damage the intestinal surface or mucosa of the bowel, because the bacteria can produce harmful toxins. This can result in leaky gut syndrome and acquired lactose intolerance. The leaky gut syndrome is controversial and associated with many symptoms that may overlap with MS-related symptoms. Leaky gut syndrome is not medically defined, and no specific tests or treatments are available. In comparison, acquired lactose intolerance occurs when someone loses the ability to digest lactose, the main sugar in milk, which causes them to develop diarrhoea, gas and bloating after eating or drinking dairy products. If you have lactose intolerance, you quickly learn to avoid lactose-containing products or use lactase preparations that help digest lactose. Please note that cheeses and yoghurt are generally tolerated because the bacteria used in the culturing process to produce these dairy products break down the lactose.

We know that many bacterial overgrowth products can impact human metabolism and behaviour. For example, people with liver dysfunction can’t metabolise these bacterial toxins and they develop hepatic encephalopathy. People with neurological disorders with reduced brain and cognitive reserve tend to be more susceptible to the effects of these bacterial metabolites, which are thought to upregulate innate immunity in the nervous system. This is why I try to stress to my patients that they should manage their constipation to prevent this from happening. Severe constipation and faecal impaction should be viewed as a chronic infection and managed and treated.

Diagnosis of SIBO

A breath test is most commonly used to diagnose SIBO. This noninvasive test measures the amount of hydrogen or methane you breathe out after drinking a mixture of glucose and water. A rapid rise in exhaled hydrogen or methane indicates bacterial overgrowth in the small intestine. Although widely available, breath testing is less specific than other tests for diagnosing bacterial overgrowth.

The gold standard for diagnosing SIBO is a small intestine aspirate and fluid culture. The fluid sample is obtained as part of a small bowel endoscopy. Other tests can include abdominal X-rays or CT scans. Faecal impaction resulting from constipation can also be diagnosed from spinal MRI scans of people with MS.

Management of SIBO

The initial way to treat bacterial overgrowth is to manage the underlying bowel hypomobility problem and clear any faecal impaction. In parallel, a course of antibiotics may be needed to reduce the number of abnormal bacteria in the bowel. However, unless you deal with the underlying problems, the bacteria will repopulate the bowel when the antibiotics are discontinued. This is why some people with SIBO may require long-term antibiotics. Switching between different antibiotics helps prevent bacterial antibiotic resistance from emerging. Please be aware that antibiotics wipe out most intestinal bacteria, both normal and abnormal; hence, they are not an ideal long-term solution to SIBO.

Starting a gut health programme is an essential part of treating SIBO. You will need a nutritional review, possibly with a dietitian, and you may need to change your diet to prevent constipation and/or faecal impaction. In some cases, you may require supplements. particularly if you are vegan.

Management of faecal incontinence

Being incontinent in public is one of the most embarrassing things that can happen to someone with MS, and it may result in social isolation to avoid experiencing the embarrassment again. Many patients with MS describe their experience of being incontinent of faeces and/or urine in public as the worst thing that has happened to them. It doesn’t have to happen; there are many ways to prevent it.

Faecal urgency needs attention (as does urgency incontinence – see section on bladder disorders). It is best treated by developing a bowel routine and trying to evacuate your bowels at a regular time of day, typically in the morning. This can be aided by using something to stimulate the bowels. I usually start by prescribing glycerine suppositories or mini-enemas. If the latter fails, I may elect to use transanal irrigation.

Transanal irrigation may sound drastic, but it often makes a massive difference to the quality of life in people with MS who need it and helps them to tackle a problem that can otherwise leave them stranded at home. I regularly refer patients for assessment to use the commercial rectal irrigation system, Peristeen, mainly because of the psychological benefits they derive from it.

The biggest problem with poor rectal compliance and faecal urgency is the odd occasion when you have diarrhoea due to gastroenteritis. With diarrhoea, whatever the cause, your rectum fills multiple times during the day and hence you are more likely to be incontinent. In this situation, you may need to use incontinence pads.

Faecal incontinence is not necessarily linked to disability. Why not? The reason is that a strategically placed MS lesion in the spinal cord can impact bowel function without causing other disabilities. I have patients who have had spinal cord relapses that leave them with faecal urgency and episodes of faecal incontinence, but very little other disability.

Case example

One patient of mine developed a severe anxiety disorder following an episode of faecal incontinence in public. She had intrusive thoughts and unpleasant flashbacks, reliving the episode repeatedly. After referral to a psychiatrist, she was diagnosed as having post-traumatic stress disorder. It took several years of counselling for her to overcome the social phobia associated with her anxiety and start going out again.

She now ventures out only after having an enema to clear her lower colon and rectum; she never eats when she is out, so as not to stimulate the reflex urge to defaecate that follows eating. She wears pads and carries a change of clothing. Her faecal incontinence emergency pack contains wet wipes, clean underwear, spare continence pads and poo bags to dispose discreetly of any used items – the same items I packed when I went out with my daughters before they were potty trained.

The importance of managing bowel dysfunction

Bowel dysfunction is one of the hidden symptoms of MS. To assess whether or not you have a bowel problem, and its severity, you can complete the Wexner Incontinence Score. Over the lifetime of the disease, most people with MS develop bowel problems, so it is important to realise that much can be done to help you. Please discuss these symptoms with your neurologist or MS clinical nurse specialist. 

On the positive side, if MS is treated early and effectively before the neuronal pathways that control bowel function are damaged, these issues can usually be avoided or delayed. Preventing disability, such as bowel dysfunction, is better than treating it. This is another critical reason to manage your MS actively with DMTs.

Bladder and bowel

Pelvic floor training

Do you have bowel, bladder and/or sexual problems? Here, I discuss pelvic floor exercises, which may help alleviate all these symptoms.

Pelvic floor exercises are one of the treatments recommended for all patients with bladder problems.1 However, when I ask patients if their continence advisors have formally instructed them on how to do these exercises, most say they were given an instruction sheet, referred to the pelvic floor exercise NHS site or other online resources. What is clear is that few people have been adhering to the pelvic floor exercise regimen; I estimate this to be less than 20% or even 10% of patients. 

  • Who should do pelvic floor exercises? 
  • Do you know how to do them and at what intensity? 
  • Have you adhered to doing them? 

Pelvic floor structure and function

The pelvic floor consists of muscles and other tissues at the bottom of the pelvis. The muscles attach to the pelvic bones and sacrum. The pelvic floor supports the lower abdominal organs and is essential for maintaining bowel, bladder and sexual function. The pelvic floor muscles have a constant tone at rest, i.e. they are tonically contracted. Voluntary and involuntary contraction and relaxation of the pelvic floor allow for normal bowel, bladder and sexual function; for example, reflex muscle contraction in response to sudden increases in intra-abdominal pressure, such as coughing or sneezing, maintains continence. Pelvic floor dysfunction causes symptoms such as urinary incontinence, voiding difficulty, pelvic organ prolapse, anal incontinence, evacuation difficulty, sexual dysfunction and pain. 

Pelvic floor muscle training

Like all muscle training programmes, pelvic floor muscle training (PFMT) is designed to improve pelvic floor muscle strength, endurance, power, relaxation or a combination of these. PFMT is typically unsupervised and self-administered. On the NHS, PFMT can be supervised by an HCP, typically a physiotherapist or a continence nurse. The National Institute for Health and Care Excellence (NICE), recommends PFMT to manage symptoms of pelvic floor dysfunction in women. NICE also recommends encouraging all women aged 12 and over to perform preventive exercises. This makes sense; the pelvic floor is just another muscle, and strengthening it should help prevent pelvic floor dysfunction in the future. Therefore, I have added PFMT to my list of exercises for my MS prehabilitation programme. 

PFMT is indicated mainly for urinary incontinence, pelvic organ prolapse and faecal incontinence. These are all problems associated with MS; in many cases MS either causes or contributes to these symptoms. 

PFMT for women

A self-administered programme should include basic voluntary contractions, which aim to improve pelvic floor muscle reaction to activities such as coughing, sneezing, exercise, and lifting, as well as sustained voluntary contractions that enhance endurance.

  • Sit comfortably with your knees slightly apart and contract the pelvic floor by lifting and tightening the muscles around the anus and vagina—as if to prevent the passage of gas and stop your urine flow.
  • Once you can achieve PFMT seated, you can perform the exercises in a standing position and during activity.
  • If you experience stress urinary incontinence (e.g. when sneezing), you can contract the pelvic floor in preparation for a leakage-provoking event; this is called the “knack”.
  • A basic voluntary contraction involves a hold of 1 ̶ 2 seconds, with the same rest time; a sustained voluntary contraction should last for 6 ̶ 10 seconds, with the same rest time. Once you establish a baseline sustained contraction, gradually increase the length of the contraction (to a maximum of 10 seconds). 

Approximately one-quarter of women cannot perform a pelvic floor contraction on their first attempt with just verbal instruction. Digital assessment of the pelvic floor – using biofeedback devices, electrical stimulation, or vaginal cones – is therefore useful to help them know when they are contracting effectively. If your progress is minimal, please ask your MS team for a referral to a suitable HCP for clinical assessment and a personalised, supervised PFMT programme.

Other resources providing useful instructions are available, e.g. a patient education leaflet from the International Urogynecological Association and smartphone applications such as the Squeezy NHS pelvic floor app. 

PFMT for men

Pelvic floor dysfunction can also occur in men, and PFMT is a recommended first-line conservative treatment. The following is an extract from the Pelvic Obstetric & Gynaecology Physiotherapy ‘Pelvic floor muscle exercises and advice for men’. 

Sit comfortably with your thighs, buttocks and tummy relaxed. Squeeze and lift the muscles from the front by either imagining you are trying to stop yourself from passing urine or trying to shorten or draw your penis up and inwards. Now try lifting the muscles from the back as if stopping the escape of wind. When you feel you have the hang of it, try lifting the front and back together. Don’t worry if you find it too difficult; after some practice, you will find the easiest and most comfortable method. This is a pelvic floor muscle contraction. To check that your pelvic floor muscles are working correctly: 

  • Place your fingers on your perineum. You should feel the perineum lift upwards as you contract your muscles.
  • Stand in front of a mirror; when you do a pelvic floor muscle contraction, you should see the base of your penis draw inwards and your testicles/ scrotum lift. 

Try not to hold your breath while you contract your pelvic floor. You are more likely to breathe easily if you lift your pelvic floor on your out-breath. Do not actively clench your buttocks, but don’t be concerned if you simultaneously feel a tightening in your buttocks and/or lower abdomen. This is normal. If you cannot feel a definite tightening in the pelvic floor muscles, you should seek professional advice.

Reference

  1. Kajbafvala M et al. Pelvic floor muscle training in multiple sclerosis patients with lower urinary tract dysfunction: A systematic review and meta-analysis. Mult Scler Relat Disord 2022;59:103559. 

Other treatments

Off-label disease-modifying therapies

Resource-poor countries do not have the benefit of all the disease-modifying therapies (DMTs) available in the UK, Europe, and elsewhere. Here I discuss some of the alternative treatments for MS that can be used when the choice of licensed DMTs is limited; I also consider some global initiatives that have provided or could provide additional ways to access some essential DMTs.

Key points

  • ‘Off-label’ prescribing describes the use of a drug for an unapproved clinical indication, where significant scientific evidence exists that it is effective; it also includes the use of a drug in a country where it does not have marketing authorisation from the local drug regulatory agencies, even though it is approved for use elsewhere.
  • We present here a list of ‘essential off-label DMTs’ that may be used in some situations to treat MS when other DMTs are not available; many clinicians consider off-label use to be better than no treatment.
  • Additional factors that limit access to some DMTs for MS include the cost of production, storage, distribution and/or clinical testing and monitoring.
  • Since the early 1990s, when interferon-beta was approved for use in relapsing ̶ remitting MS, more than 15 MS DMTs have been licensed and still more are in development.
  • In 2023, the World Health Organisation (WHO) added cladribine, glatiramer acetate and rituximab to its essential off-label DMT list; this is a step in the right direction, but there is still a long way to go in ensuring effective, accessible treatment for many people with MS.

What is ‘off-label’ prescribing?

Before a drug is licensed for medical use, it undergoes a series of clinical studies designed to test its efficacy and safety for a named condition. The clinical studies will also determine factors such as the recommended dose, who can or cannot take the drug (e.g. not children or elderly people) and any contraindications (warnings and exclusions) associated with its use in that setting. Following satisfactory completion of the necessary clinical studies, the drug manufacturer may seek a marketing authorisation from the drug regulatory agencies to promote their product for the specific ‘indication’ or indications defined by those studies.  

Drug manufacturers are not legally permitted to encourage off-label prescribing, i.e. the use of regulated drugs for any indications that a country’s government has not formally approved. However, where significant scientific evidence exists that a drug is effective for an unapproved indication, clinicians will not uncommonly prescribe it ‘off-label’ if they believe that using that treatment confers more benefit than no treatment. Off-label use is generally legal unless it violates ethical guidelines or safety regulations. In the case of MS, off-label treatments may be the only option for patients in resource-poor countries or settings, for example, refugees or illegal immigrants without healthcare coverage in high-income countries.

I firmly believe that treating MS with an off-label medication is better than no treatment. The drugs listed in the table below are the options I have recommended in the past for people with MS from resource-poor countries. I call this my ‘essential off-label DMT list’, and it consists of drugs that are not licensed to treat MS but have a sufficient evidence base to give neurologists the confidence that they work. Not all of these will be available or appropriate for your county.

Drugs table updated format 190625 SS

Drugs that are not currently licensed for the treatment of MS but are used in some situations to treat it ‘off label’. Please note that the DMTs included in this list are those recommended by Professor Giovannoni. Cladribine and rituximab are recommended for MS by the World Health Organisation as part of their Essential Medicines List.
HSCT, haematopoietic stem cell transplantation; IRT, immune reconstitution therapy.
* Included in the 23rd WHO Model List of Essential Medicines; **Converted to teriflunomide; ‡ Licensed for MS in some countries but not the UK.

Please note that cladribine in tablet form is licensed for MS in the UK and elsewhere and has recently been added to the list of essential medicines recommended by WHO (see later). Though not licensed for MS, administration by injection or infusion probably has similar efficacy and side effects to the tablet formulations, but this has not yet been established in large phase 3 clinical trials. However, the alternative parenteral formulations may be more accessible in resource-poor countries for oncological indications.

The MS-Selfie InfoCards on our website provide additional information about each drug listed above, including duration and frequency of dosing, assessment of their effectiveness in preventing relapses and long-term disability, and the likely frequency of short-term and long-term side effects.

Access to effective DMTs varies widely

Another factor that restricts availability is cost. Many of the DMTs available in the UK, Europe and other ‘first-world’ countries are simply too expensive for low- or middle-income countries, so their access is limited in those regions. Many newly licensed DMTs fall into this category; once their patents expire, the costs will likely come down because of competition from other companies that can make unbranded, generic copies or biosimilar formulations. This takes time, however.

In some countries, though, even the older, less expensive DMTs are unavailable. The requirements for storing, distributing, administering or monitoring them may be prohibitive, even if the cost of the drugs is not. Below are some case examples of people with MS who have contacted me for advice on how to obtain a treatment for their MS; in such situations, an unlicensed treatment may be the only option.

Access problems are not only experienced in low- or middle-income countries; they can also affect people with limited means living in ‘first-world’ countries.

Advent of effective MS treatments

Shortly after I arrived in London in 1993, the pivotal trial results for interferon-beta-1b in relapsing ̶ remitting MS were announced. Interferon-beta was not the first therapy to be shown to modify the course of MS, but it was the first treatment to be licensed.

Interferon-beta catalysed a remarkable era in MS treatment, transforming the clinical course of the disease. In the past, patients were admitted to the hospital for management of a relapse, a diagnostic work-up or to treat complications of MS, such as pressure sores. Nowadays it is rare for someone with MS to be an inpatient on a neurology ward because current DMTs are so effective at managing the disease. We now have more than 15 products licensed for MS, and more in development. 

Identification of essential ‘off-label’ DMTs

In 2014, I took a 6-month sabbatical and travelled to see how MS was managed globally; I visited MS centres in the US, Canada, Europe, Australia, South America, India, Egypt, the Middle East and South Africa. The situation in India and South Africa shocked me the most. In India, for example, fewer than 2% of people with MS were on DMTs. Unless you were wealthy and had private health insurance your MS was essentially left to run its natural course. This was what prompted me to start my essential off-label DMT list of drugs not licensed to treat MS but with strong evidence that they are effective (see back). <add hyperlink to table p2>

Did this list change things? Almost certainly. When I visited India recently, a leading MS neurologist thanked me for nudging the Indian neurologists to start using off-label rituximab. I was told that around 30 ̶ 40% of people with MS were now receiving a DMT – a considerable increase from 2% in 2014. Moreover, many middle-income countries have implemented state-funded MS treatment programmes. Things do change; it just takes time. 

World Health Organisation’s Essential Medicines List

The World Health Organization (WHO) publishes a biennial Essential Medicines List (EML) to assist governments in low-resource settings to prioritize their spending on medicines. In 2015, I began a collaboration with MSIF (Multiple Sclerosis International Federation) to campaign for better access to MS DMTs worldwide. The MSIF Off-Label Treatments (MOLT) initiative resulted in two submissions to the WHO to get MS DMTs onto the WHO Model List of Essential Medicines.

For the first EML submission (the 2019 list), the MSIF taskforce categorized 15 DMTs according to their efficacy and risk profiles to ensure maximum clinical versatility. Three DMTs were selected: glatiramer acetate, fingolimod and ocrelizumab. The WHO Expert Committee declined to add any of these to the EML but requested a revised application. The subsequent application included cladribine, glatiramer acetate and rituximab. In 2023, the WHO green-lighted these three drugs, and they are now on the EML for treating MS.2    

Rituximab is the first-generation anti-CD20 therapy that depletes peripheral B-cells and was the forerunner of ocrelizumab, a more humanised monoclonal anti-CD20 therapy. A phase 2 trial of rituximab showed that it is a very effective treatment for relapsing MS and was subsequently widely used off-label to treat MS. The wide availability of affordable rituximab biosimilars, real-world evidence of its effectiveness in MS, were the main reasons for the WHO to prioritise rituximab over ocrelizumab and other anti-CD20 therapies.

DMTs for MS now included in the 23rd WHO Model List of Essential Medicines since 2023.

Glatiramer acetate (GA) was chosen because of its safety profile, absence of monitoring requirements and good track record during pregnancy. However, it is a complex therapy with high manufacturing requirements, and therefore not particularly cheap. The cold-chain storage and distribution requirements for GA may be problematic in certain healthcare environments. 

Rituximab may prove the most controversial DMT on the WHO’s EML. Although it is widely used, we still don’t know the optimal dose. Rituximab also has cold-chain and several logistical delivery requirements. There is an issue around anti-drug antibodies (ADAs), which the body produces against a drug, that can potentially interfere with its effectiveness or cause adverse reactions; for further information, see section on anti-CD20 therapies. Assays for ADAs are challenging to access in resource-poor settings. Finally, rituximab is a biological therapy, and the costs remain relatively high. Once ocrelizumab comes off-patent, and biosimilars enter the market, the WHO may wish to consider replacing rituximab with ocrelizumab. The evidence base for ocrelizumab for both relapsing and primary progressive MS is superior to that for rituximab, ADAs are less of a problem and the dose is well established. 

Cladribine was chosen because it is a tablet with a good safety profile, low monitoring requirements and good efficacy as an immune reconstitution therapy. Oral cladribine is still protected by a patent, but when this expires the price will plummet. In the interim, the parenteral formulation can be used by injection or infusion. Cladribine will be the real game-changer.

I can’t overstress the importance of WHO’s decision to include three MS DMTs in the EML. Firstly, the WHO now acknowledges that MS and its treatment are global-level problems. Secondly, low- and low-middle-income countries will now have to recognise that MS is a treatable condition, and they will hopefully now be forced to include the diagnosis and management of MS as part of their healthcare plans.

Other ways to increase access to effective DMTs

Neurologists in resource-poor environments must act locally and start grass-roots movements in their own countries to get MS diagnosed, managed and cared for properly, including off-label prescribing. Patient organisations can participate in this too. Many patient organisations support compassionate access schemes even if they oppose off-label prescribing as a solution to the management of MS.

The Medicines Patent Pool (MPP), a United Nations-backed public health organisation, is exploring another avenue. This is a market solution, whereby the MPP licenses patents of high-cost drugs from pharmaceutical companies and then sublicenses them to generic companies to produce a generic equivalent for low- and middle-income countries. This model has worked very well for HIV and hepatitis C. Although the MPP does excellent work, it takes time for things to happen and does not address this patient’s unmet need in the present. 

Conclusions

I have outlined my rationale for using off-label DMTs in situations where licensed options are not available or are hard to access. Let’s suppose that limited access to an effective DMT affects you, as a person with MS. In that case, I recommend approaching your neurologist or other healthcare professional with this information and discussing the possibility of being treated with one of these agents. No one drug is ideal for everyone. The attributes of each treatment vary, as does their availability. Therefore, what is available in one country or healthcare environment may not be available in another. In general, if you have active MS, it is better to be treated than not to be treated. Off-label DMTs should be used in the same way as licensed therapies, based on a treat-to-target of no inflammatory disease activity. If there is breakthrough disease activity, the treatment must be escalated to another more effective treatment.

References

  1. McDonell J. et al. World Health Organization Essential Medicines List: Multiple sclerosis disease-modifying therapies application. Mult Scler 2020;26:153 ̶ 8.
  2. WHO endorses landmark public health decisions on Essential Medicines for Multiple Sclerosis. WHO Press Release, 26 July 2023.
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

Sleep disrupted by pain and discomfort

Here I provide some practical guidance on managing the discomfort of being unable to turn in bed and suggest ways to reduce unpleasant sensations in the legs from restless legs syndrome (RLS) and other conditions that can hinder sleep.

Key points

  • Stretching, exercises, medication and various physical devices and aids can help relieve your discomfort if you have difficulty rolling over in bed at night.
  • RLS is common in people with MS; it has been associated with poor attention and concentration, memory issues, decreased productivity, depression and anxiety.
  • It is important to get treatment for RLS. Before doing so, please check if it is caused by MS or by another condition, such as renal dysfunction, low iron levels or pregnancy.
  • Various drugs are effective in controlling RLS symptoms, and some lifestyle changes and activities may relieve mild to moderate RLS.
  • Other unpleasant, painful sensations in the legs may disrupt sleep in people with MS and need to be managed.
  • Addressing these and other causes of poor sleep is essential to improving the functioning and quality of life of people with MS.

Among the MS symptoms that contribute to fatigue and insomnia in people with MS, several conditions deserve special mention because of the extreme pain or discomfort they cause. They include being unable to turn in bed, restless legs syndrome (RLS) and other unpleasant or uncomfortable sensations in the legs. 

Pain from being unable to roll over

In November 2020, I was hit by a speeding motorcyclist while out jogging. Thankfully, I have made a reasonable recovery, with minor residual problems, and the horror of the accident is gradually receding from my memory. My post-traumatic flashbacks, typically triggered by the sound of a speeding motorbike, are now quite rare.

The one thing that still haunts me, however, is the chronic insomnia I experienced due to the pain and discomfort of not being able to roll over in bed. For about 6 months, I had to sleep on my back, unable to move because of a fractured pelvis and a neck brace. I can now appreciate what my patients go through when they have neuralgic pain or insomnia.

If you have problems rolling over in bed at night, there are things you can do to help yourself. 

  1. Stretching and range of motion exercises: doing gentle stretching and range of motion exercises during the day can help improve flexibility and reduce muscle stiffness, making it easier to roll over in bed at night.
  2. Physical therapy: please see a physiotherapist or physical therapist who can provide a personalised exercise programme and teach you techniques to address specific mobility issues and improve overall movement.
  3. Medication: ensure you have been assessed and prescribed appropriate medications to manage muscle spasticity and spasms, and pain during the night.
  4. Supportive devices: utilising supportive devices such as bed rails, grab bars, monkey ropes or specially designed pillows can provide additional assistance and stability when transitioning in bed.
  5. Low-friction bed linen and pyjamas: using satin or low-friction linen and pyjamas can make the difference of being able to roll over in bed or not. 
  6. Specialised beds: if all else fails, you may need to purchase a tilting bed that helps automate the process of rolling over. However, these beds are relatively expensive and are not generally covered by NHS budgets. 
  7. A comfortable sleep environment: creating a comfortable and supportive sleep environment, including a supportive mattress and pillows, can help reduce discomfort and make it easier to roll over at night.
  8. Remember that the current treatment strategy for MS is to maximise your brain health, and part of this philosophy is holistic management, including sleep.

Restless legs syndrome

RLS is experienced as an unpleasant or uncomfortable sensation in your legs and an irresistible urge to move them. The symptoms usually occur in the late afternoon and evening and are most severe at night in bed. An essential diagnostic tip is that moving your legs relieves discomfort, but it recurs once leg movements stop.

RLS in people with MS

RLS is very common in people with MS; it causes or exacerbates insomnia and is strongly linked to daytime sleepiness and fatigue, affecting your mood and your daytime functioning. People with RLS may have poor attention and concentration, memory issues, decreased productivity, depression or anxiety. Cederberg et al1 have demonstrated that restless legs syndrome affects sleep quality and is associated with poor cognition in people with MS. RLS may go into remission for weeks or months; however, symptoms often reappear and become more severe over time. So, if you have RLS, bring it to the attention of your HCP so that you can get it treated.

A study conducted in Saudi Arabia2 found that 30% of 109 people with MS fulfilled the diagnostic criteria for RLS, defined by meeting all four requirements of the International Restless Legs Syndrome Study Group diagnostic criteria; this compared with 8.3% with RLS in a group of 216 healthy controls. In my clinic, the percentage of people with MS experiencing RLS is lower than this – closer to 10% – but I may be wrong as I don’t use a validated screening tool when checking for this.

Other conditions associated with RLS

RLS is commonly experienced by people with end-stage renal disease who are on haemodialysis. Other conditions associated with RLS include neuropathy, sleep deprivation, vigorous exercise (e.g. in athletes), pregnancy and menopause. Alcohol, nicotine, caffeine, antiemetics, antipsychotics, antidepressants that increase serotonin and over-the-counter cold and allergy medications containing older antihistamines are also associated with RLS. 

If you have RLS, you should not assume that it is due to MS. You must have a medical history taken and a thorough neurological and physical exam (possibly including blood tests) to exclude other causes of RLS, such as renal dysfunction, low iron levels or pregnancy. A sleep study may also be indicated to check for another sleep disorder, such as sleep apnoea.

Treatment of RLS

There is no cure for RLS, but some symptoms can be treated. As mentioned earlier, moving your affected limb(s) may provide temporary relief. Sometimes, RLS symptoms can be controlled by treating an associated medical condition, such as peripheral neuropathy, diabetes or iron deficiency anaemia. Peripheral iron levels, particularly in the spinal fluid, can be lower than expected and don’t always respond to oral iron supplements; in such cases, intravenous administration of iron may help. 

In my experience, the best treatment for RLS is one of the gabapentinoids, i.e. gabapentin or pregabalin. Many neurologists still use dopamine agonists such as ropinirole, pramipexole and rotigotine. However, daily long-term use of dopaminergic drugs can eventually worsen symptoms and is associated with complications. Opioids may be effective if the gabapentinoids fail; my recommendation would be to use methadone, as it has the lowest risk of addiction. 

In the case of comorbidity such as spasticity in people with MS, benzodiazepines may be prescribed (clonazepam, diazepam or lorazepam). However, benzodiazepines are associated with tachyphylaxis, i.e. the body gets used to the effects, and the dose must be increased to maintain the same treatment effect. They are addictive and cannot be stopped suddenly.

Some lifestyle changes and activities that may relieve mild to moderate RLS are listed below.

  1. Avoid or decrease the use of alcohol, nicotine and caffeine.
  2. Establish or maintain a regular sleep pattern.
  3. Try moderate, regular exercise rather than intermittent vigorous exercise.
  4. Massage the legs.
  5. Try a warm bath.
  6. Apply a heating pad or ice pack.
  7. Use foot wraps specially designed for people with RLS.
  8. Try vibration pads on the back of the legs.
  9. Do leg-stretching exercises of moderate intensity.
  10. Try magnesium supplements.

Other causes of leg discomfort

People with MS have discomfort in their legs at night for many reasons, and not all restless legs are due to the RLS. A proper examination is needed before making specific treatment recommendations.

Spasticity

Spasticity and nocturnal leg jerks most commonly mimic RLS. Spasticity tends to go hand in hand with lower limb weakness and should be treated with antispasticity agents. These include baclofen, tizanidine, gabapentin, pregabalin, clonazepam or other benzodiazepines, tetrahydrocannabinol (THC), other CB1 agonists (nabilone), and – rarely nowadays – dantrolene, a direct muscle relaxant.

Pain syndromes

Myelopathic pain (i.e. pain resulting from spinal cord disease) is common in people with advanced MS and often causes leg discomfort. Pain syndromes must be managed with centrally acting pain medications such as duloxetine, tricyclic antidepressants and gabapentinoids. Tetrahydrocannabinol (THC; Sativex and Dronabinol) and other CB1 agonists (nabilone) are also effective. Many people with MS use cannabidiol (CBD) as monotherapy and claim it works. Currently, there is only one licensed form of CBD for epilepsy, and it can’t be prescribed for pain. Many patients, therefore, purchase CBD online; I cannot recommend this because of the risk of contaminants. In addition, CBD is associated with liver toxicity; therefore, liver function tests should be done to monitor for this problem. Many people with MS use street or medicinal cannabis, which, although legal for medicinal use, can’t be prescribed under the NHS. Private clinics in the UK, both physical and online, are filling the gap. I have little doubt that cannabis helps people with MS get a better night’s sleep, particularly those with pain and spasticity.

Cramps

People with MS are as likely, if not more likely, to experience leg cramps as people in the general population. Leg cramps are usually easily differentiated on history from other nocturnal leg movements and are managed accordingly. Below are some tips for managing leg cramps.

  1. Regular stretching exercises can help prevent leg cramps.
  2. Staying well hydrated is important. Dehydration can contribute to muscle cramps, so drinking adequate water throughout the day is essential, particularly during physical exertion or in hot weather.
  3. Maintaining a proper balance of electrolytes such as potassium, calcium, and magnesium is crucial to prevent leg cramps. This is where diet and supplements can be important. 
  4. Massaging the affected leg can relieve leg cramps. Apply gentle pressure to the cramped muscle and rub it using a circular motion. 
  5. Medications may be required if cramps are common and affect your sleep. Some people with MS find some relief from simple over-the-counter analgesics such as ibuprofen or paracetamol/acetaminophen. Other medications must be prescribed, including quinine, calcium channel blockers and gabapentinoids. 


Periodic limb movements of sleep (PLMS)

PLMS are characterised by involuntary leg twitching or jerking movements during sleep. The movements are very sudden jerks and are due to myoclonus. They can occur every 15 seconds, sometimes throughout the night. Although many individuals with RLS also develop PLMS, most people with PLMS do not experience RLS. In general, PLMS responds to measures similar to those used for RLS, i.e. gabapentinoids, methadone and dopamine agonists. Dopamine agonists are best avoided because of the augmentation that occurs, i.e. the condition worsens. Other medications that may help include clonazepam, melatonin, anticonvulsants and selegiline. I have no personal experience of prescribing melatonin or selegiline for PLMS.

Conclusion

MS-related symptoms that cause pain or discomfort in bed and disrupt sleep contribute to daytime fatigue and impact physical and mental function. As a result, poor sleep reduces quality of life and can exacerbate other MS-related problems such as poor concentration, anxiety and depression. Any such hindrances to healthy sleep should be documented, investigated appropriately and treated accordingly to improve the functioning and quality of life of people with MS.

References

  1. Cederberg, KLJ et al. Restless Legs Syndrome, sleep quality, and perceived cognitive impairment in adults with multiple sclerosis. Mult Scler Relat Disord 2020;43:102176.
  2. Aljarallah S et al. Restless leg syndrome in multiple sclerosis: a case-control study. Front Neurol 2023;14:1194212. 
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.