Tag Archives: sperm

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.

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

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

Key points

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

Standard tests … and why we do them

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

Baseline tests

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

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

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

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

Infection screening

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

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

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

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

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

Vaccinations

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

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

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

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

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

Cardiovascular screening

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

Pregnancy, family planning and genetic testing

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

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

Protecting against progressive multifocal leukoencephalopathy

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

Prophylactic antivirals and antibiotics

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

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

Infusion reactions

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

Ongoing monitoring

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

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

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

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


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

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

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

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