Rationale and impact
- Diagnosing multiple sclerosis
- Providing information and support
- Coordination of care
- Assessment and non-pharmacological management of fatigue
- Pharmacological management of fatigue
- Pharmacological management of mobility problems
- Cognitive and memory problems
- Pharmacological management of ataxia and tremor
These sections briefly explain why the committee made the recommendations and how they might affect practice.
The recommendations were updated to reflect changes to the McDonald criteria, revised 2017 (Thompson AJ, Banwell BL, Barkhof F et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria, The Lancet Neurology), which are expected to speed up diagnosis and reduce the chance of misdiagnosis. The committee agreed that the previous recommendations on diagnosis are still relevant, but made some updates based on their experience and changes to practice since 2014.
The committee retained the recommendations on symptoms and features of multiple sclerosis (MS), highlighting that symptoms can be wide-ranging and listing the most common symptoms and those that would make a diagnosis unlikely.
The committee agreed that assessments to exclude alternative diagnoses need to be tailored to the person, according to their presenting symptoms. They decided that a list of blood tests would not be helpful and that tests would need to be decided on an individual basis.
The committee agreed that a consultant neurologist should be responsible for the diagnosis of MS, using the history, examination, MRI and other test findings, and by following the revised McDonald criteria. To meet the updated criteria, dissemination of lesions in the nervous system in space and time needs to be demonstrated, and all lesions visible on an MRI scan can contribute to the criteria, irrespective of whether they have caused symptoms (symptomatic lesions) or have not caused symptoms (asymptomatic lesions). A positive finding of cerebrospinal fluid oligoclonal bands can now be used in place of dissemination of lesions in some circumstances. The criteria have been developed for people experiencing clinically isolated syndrome, which means that they must present with symptoms suggestive of an inflammatory demyelinating condition.
The committee agreed to retain the previous recommendation on reviewing people with suspected MS who do not meet the McDonald criteria, but added the example of reviewing people annually, which is in line with current practice. They agreed that information should be provided so that people understand why they need to be reviewed regularly and who to contact if their symptoms change or they have concerns.
The committee supported the importance of providing information and advice on resources at the time of diagnosis.
The recommendations are expected to help to reduce variation between services and clinicians. The recommendations reflect current clinical practice and are not expected to increase the number of referrals or the cost of making a diagnosis and therefore will not have a substantial resource impact.
The committee noted that people who were diagnosed with MS a long time ago may not be offered an annual review. They highlighted the importance of informing people with MS and their carers that they should have a regular comprehensive review so that they can ensure that this takes place at least once a year and covers all of their needs.
The evidence showed that MS has a significant impact on carers and that information and support for them was often lacking. Carers are not always aware of the support available to them and often do not have the information they need as circumstances change for the person with MS. The committee agreed that carers should be aware of their right to a carer's assessment and highlighted that this should include assessments for young carers.
The committee also noted that the timing of information was important and agreed that information and support should be provided according to the changing needs or circumstances of the person with MS. Considering pregnancy and approaching more advanced disease were identified as particular situations in which information and support needs should be reviewed. The committee made specific recommendations for these groups.
No evidence was identified on the information and support needs for people diagnosed with clinically isolated syndrome, and the committee therefore made a recommendation for research on information and support for people with clinically isolated syndrome.
Recommendations from the previous version of the guideline were updated and new recommendations added, based on qualitative evidence and the committee's experience. The committee agreed that the recommendations should apply to both women and men planning to start a family, where appropriate, and to people considering adoption as well as those planning pregnancy.
The committee agreed that discussions about starting or extending a family should happen early to ensure that people with MS have time to make decisions and plan for the future. They agreed that healthcare professionals should proactively ask about and discuss the person's plans for having children. The committee noted that some people with MS assume that they cannot have children and do not ask for advice. Although there was limited evidence supporting early information giving, the committee agreed that, based on their experience, it is important to start these discussions soon after diagnosis.
The committee noted that some disease-modifying treatments should not be taken during pregnancy because of the risk of harm to the unborn baby. Therefore, they highlighted that people taking these treatments need to inform their healthcare professional straight away if they are trying to get pregnant or become pregnant.
The evidence showed that people with MS often have concerns about the impact of MS on having a family. The committee agreed that MS should not be a barrier to planning a family, because pregnancies can be well managed and additional support may be available. Many people with MS may feel like they are not able to have children, so the committee agreed that people with MS should be able to discuss the possibilities before making these decisions.
The evidence highlighted issues of particular concern to people with MS, such as how MS and treatments can affect pregnancy, whether they can pass MS on to their children and the impact of MS on their labour, birth options and breastfeeding. People also wanted more information on the possible impact that caring for a child might have on their symptoms, such as fatigue, and advice on how to manage this. The committee updated the existing recommendations based on the evidence. Based on their experience, the committee also included a reference to advice on folic acid in the NICE guideline on maternal and child nutrition because they agreed that this would also apply to people with MS.
Information and support for people as MS becomes advanced, including those approaching the end of their life
The qualitative evidence showed that feelings of social isolation and depression are common in people with MS, but they often lack information about available services and support. It also showed that people were not always aware of the availability and suitability of home adaptations and mobility aids, and how to obtain them. These are important for maintaining independence as MS progresses. Other areas were also identified where better information and support could improve the experience and wellbeing of people with MS and their carers, including legal rights, employment rights, benefits and carer assessments.
Based on the evidence and their experience, the committee agreed that people with advanced MS and their carers need information and support to navigate services so that they can access extra support as their needs change.
The committee noted that NICE's guideline on end of life care for adults includes recommendations on providing information and support for people who may be approaching the end of their life. They also agreed that an existing recommendation on advance care planning and power of attorney should be retained because it is still supported by the evidence and it is important to help people plan for their future care. It was updated to include a cross reference to NICE's guideline on decision-making and mental capacity. The committee added that early discussions about advance care planning should be considered for people at risk of deterioration.
The recommendations are in line with current good practice. Overall, the committee did not think these recommendations would have a significant resource impact.
The committee updated the 2014 recommendation to emphasise that the point of contact should have knowledge of MS services to coordinate the person's care and help them access relevant healthcare professionals. The available clinical and health economic evidence was limited, so the committee were not able to specify that the point of contact should have knowledge of MS because this may represent a change in practice and a significant resource impact. Instead, a point of contact with access to appropriate healthcare services was specified to allow for different service configurations; for example, the point of contact would be able to access a healthcare professional who can contact the person with MS and respond to their concerns. The committee acknowledged the lack of evidence in this area and made a recommendation for research on coordination of care for people with MS to support future guidance in this area.
The recommendation emphasises that the point of contact should have knowledge of MS services. This should not result in a large change in practice and therefore will not have a significant resource impact.
Although a large number of studies have been published since the previous version of the guideline, the committee agreed that the new evidence was too limited in quality to change most of the existing recommendations. However, the new evidence did further support the 2014 recommendations on managing MS-related fatigue.
Fatigue may not always be identified and treated, so the committee agreed by informal consensus that people with MS should be asked about the presence of fatigue. Causes of fatigue other than MS may sometimes be missed, so the committee highlighted the importance of checking for other possible causes, to ensure appropriate management.
There was some evidence that fatigue or energy management interventions and wellbeing techniques, such as cognitive behavioural therapy (CBT) and mindfulness, are beneficial. However, the committee agreed that the evidence was not sufficient to recommend formal programmes because of limitations in the studies. Instead, the committee recognised that using elements of these approaches could be helpful and included in discussions about self-management options.
Based on their experience, the committee agreed that a fatigue management discussion should be offered, which is routinely provided in current practice. This would be a tailored discussion that could include goals and priorities for each person, advice on energy conservation, review of lifestyle factors and the use of stress reduction and wellbeing techniques, including cognitive behavioural principles for managing day-to-day activities and mindfulness-based techniques.
The committee agreed that the previous recommendation on advice about the possible benefits of aerobic, balance and stretching exercises, including yoga, was still supported by the evidence. In addition, there was some evidence of benefit for progressive resistive exercises and pilates.
There was a lack of evidence on specific diets, but a recommendation was made to highlight the benefits of following a healthy diet. Diet was also included in the discussion of fatigue management.
The committee agreed that the evidence still supported the previous recommendation on considering a programme of aerobic and moderate progressive resistance activity combined with cognitive behavioural techniques to treat fatigue in people with significantly impaired mobility (EDSS [Expanded Disability Status Scale] score of at least 4). This was based on clinical evidence, modest economic evidence (covering the ExIMS study, 2013) and the original economic analysis from the previous version of the guideline supporting the cost effectiveness of combined exercise programmes. The committee noted that this should be a supervised programme provided to the person with MS, rather than self-directed exercise, and that it should be tailored to the needs and abilities of the person.
No randomised controlled trial evidence was identified for hyperbaric oxygen to treat MS-related fatigue in people with MS. The committee were concerned that this intervention is being used despite the lack of evidence, sometimes at the expense of the person with MS or through charities. They agreed that it should not be used, based on the lack of evidence, their clinical experience and the high cost involved.
A recommendation for research on identifying clinically and cost-effective interventions for the non-pharmacological management of fatigue was developed to encourage further research in this area.
The recommendations on assessment and offering people a personal tailored discussion about fatigue management do not represent a change in practice. Discussion of fatigue management is provided routinely in current practice by occupational therapists, MS nurses or physiotherapists. It does not typically involve a specific, structured fatigue management programme but includes some elements of fatigue management, such as advice on energy conservation. Similarly, the inclusion of stress and wellbeing techniques does not refer to structured interventions but allows the opportunity to use some elements of these techniques as part of the fatigue management discussion, which the committee agreed are used as part of fatigue management discussions in current practice.
Supervised aerobic and moderate progressive resistance programmes with cognitive behavioural techniques for people with an EDSS score of at least 4 was recommended in the 2014 guideline based on clinical- and cost-effectiveness analysis. Physiotherapists and occupational therapists typically apply CBT principles like goal setting as part of exercise interventions in current practice, and this does not need to be a formal CBT intervention delivered by a psychologist. The committee agreed that this would not represent a change in practice.
Recommendations covering advice on exercises for MS-related fatigue (which would be self-directed exercise rather than supervised programmes provided to the person with MS) and following the principles of a healthy diet are consistent with current good practice, as is the recommendation not to offer hyperbaric oxygen.
As none of the recommendations represent a change in current practice these recommendations are not expected to have a resource impact.
The evidence for treating fatigue with amantadine, modafinil or selective serotonin reuptake inhibitors (SSRIs) in people with MS was limited but showed some benefit for each medicine. The lack of good evidence comparing the different treatments meant that the committee were unable to recommend one in preference to the others or an order in which these treatments should be considered. However, they agreed that fatigue can have a significant impact on the person's daily activities and that, in their clinical experience, it can improve with pharmacological treatment in some people.
Amantadine, modafinil and SSRIs are not licensed for treating fatigue in people with MS and there are safety issues associated with their use, so they should only be started by a specialist in MS. The committee agreed that the potential benefits of effective treatment may outweigh the risks for people whose quality of life is severely affected by fatigue. However, they highlighted that people with MS should be fully informed about the possible risks and benefits, and make a shared decision with a specialist about whether to try a medicine and which would be most suitable, taking into account their needs, priorities and preferences. They agreed that it is important that people can access pharmacological treatment options and that they can be considered before trying non-pharmacological treatments in people for whom a rapid response is a priority.
The committee highlighted the particular safety concerns for modafinil, including that it should not be used by people who are pregnant or planning pregnancy, and that precautions should be taken if prescribing it for people able to get pregnant, in line with the 2020 Medicines and Healthcare products Regulatory Agency (MHRA) safety advice on modafinil. The committee noted additional advice for modafinil on monitoring, stopping treatment and cautions for use in the 2014 MHRA safety advice on modafinil and advice in the summary of product characteristics for modafinil and amantadine. Based on their experience, the committee highlighted the importance of starting people on a low dose of modafinil, such as 100 mg once a day.
The committee agreed that people taking these medicines would need to have regular reviews to monitor effectiveness and safety, adjust dosages and ensure that treatment is stopped if it is ineffective or the person experiences adverse effects. If treatment is effective and the person is on a stable dose of their medicine, the committee agreed that responsibility for prescribing could be transferred to primary care under a shared-care arrangement.
A recommendation for research on the pharmacological management of fatigue was made to support future research in this area.
Amantadine is currently prescribed as the first-line pharmacological treatment, alongside non-pharmacological management options, as a part of a multidisciplinary approach to fatigue. Modafinil and SSRIs are less commonly prescribed. These pharmacological treatments are usually prescribed under the guidance of secondary care specialists. The recommendations may result in a change from current practice, with increased prescribing of modafinil and SSRIs. There may also be an increase in the use of shared-care arrangements for prescribing these medicines in primary care.
There may be a resource impact due to cardiovascular monitoring from the increased use of modafinil in a broader range of clinical settings, including primary care. However, the recommendations may result in a decrease in the use of amantadine, which has a greater unit cost than modafinil and SSRIs. Therefore, the overall resource impact of the recommendations is unlikely to be significant.
Fampridine was shown to be effective in treating lack of mobility in some people with MS, but not all. A health economic analysis was carried out for this guideline update, which included modelling an initial 4‑week assessment to identify which people with MS respond to and would then continue fampridine treatment. Based on the current list price, fampridine was not found to be a cost-effective treatment and so the committee made a recommendation to not offer fampridine for the management of mobility problems.
This recommendation does not represent a change in practice and therefore will not have a resource impact.
There was very limited new evidence on pharmacological management of spasticity. Only 1 study comparing intrathecal baclofen to usual care in a post-stroke population was identified. This evidence was insufficient to make any new recommendations or significant changes to the previous guideline recommendations. Therefore, the committee updated the 2014 recommendations based on their experience and knowledge of current practice.
The committee agreed that it is important to raise awareness of spasticity and its presentation to ensure that people with MS receive appropriate treatment. They also highlighted that it is important to emphasise that the management of spasticity in MS should be tailored to the needs of the person and their specific treatment goals because spasticity can vary significantly in people with MS and change at different stages in the course of their disease. The committee agreed that the previous recommendation on assessing for and treating factors that may exacerbate symptomatic spasticity should be retained.
The committee were aware that some people with MS use their spasticity to support them in maintaining posture when transferring or standing, and they agreed that the treatment of spasticity can have the potential to cause greater levels of disability. It was, therefore, agreed that the balance of risks and harms of treatment need to be fully discussed with the person before agreeing treatment.
Although there was no new evidence on specific pharmacological treatments for spasticity, the committee took into account safety concerns for the use of gabapentin (see the 2019 MHRA drug safety update on pregabalin, gabapentin and risk of abuse and dependence) and agreed that it should no longer be recommended as a first-line option. The combination of baclofen and gabapentin is offered when neither agent by itself manages to control symptoms, but this needs to be balanced against the possible side effects. The committee noted that the BNF states that both gabapentin and baclofen can have central nervous system (CNS) depressant effects, which might affect the ability to perform skilled tasks. There is also a potential increased risk of respiratory depression (as advised by the MHRA) when using gabapentin in combination with other CNS depressants, and people with neurological disease (such as MS) may be at higher risk of this. The committee discussed the safety issues for gabapentin and agreed that illegal diversion and misuse are of particular concern. However, they agreed that gabapentin can be an effective treatment and should still be an option for treating spasticity in MS if oral baclofen is not tolerated or unsuccessful. Prescribers should follow the MHRA safety advice on evaluating people for a history of drug abuse and checking for misuse and dependence. The committee noted that gabapentin is now a class C controlled substance and prescribers will need to follow the statutory requirements for its use.
Based on their experience, the committee agreed that information should be added to the previous recommendation on using these medicines to clarify the importance of gradually increasing the doses of medicine to reach the optimal dosage.
The committee agreed that if a person's treatment goals are not being met by treatment with baclofen or gabapentin (alone or in combination), and appropriate physical assessments and precipitating or prolonging factors have been addressed, other treatment approaches should be considered, which may be delivered by a service dedicated to the more specialist management of spasticity. The committee updated the recommendation in the 2014 guideline on referral to specialist services to include multidisciplinary teams, which is consistent with current clinical practice.
A recommendation for research on identifying clinical and cost-effective pharmacological interventions for the management of spasticity was developed to encourage further research in this area.
The recommendations reflect current best practice in the approach to the assessment and management of spasticity in people with MS. The committee recognised that not all clinicians would have direct access to specialist spasticity management services to deliver treatments beyond initial pharmacological approaches. However, services that specialise in the management of spasticity should be available at a regional level, ideally as part of a network.
It is not anticipated that the updated recommendations will result in significantly greater resource use to support the assessment and treatment of spasticity in people with MS. There may be resource savings realised through a reduction in complications caused by inappropriate treatment or untreated spasticity.
The causes of pain in people with MS are varied. It may be neuropathic, caused by MS nerve damage; or secondary to immobility, spasticity or posture issues; or it may be unrelated to MS and caused by other comorbid conditions. Pain is sometimes assumed to be neuropathic in people with MS when it may have a different cause. Based on their experience, the committee agreed that the first step in managing pain is to investigate and establish the cause. If the underlying cause is correctly identified, it will prevent unnecessary treatment and possible side effects, and ensure pain is managed correctly.
The committee acknowledged the impact that pain can have on mental health. Pain can severely impair mobility and active lifestyle choices, which may lead to low mood and mental health problems. Low mood may also affect the way the person deals with pain. Therefore, it is important that healthcare professionals are mindful of this complex interaction and that people are offered support and advice if pain is affecting their mental wellbeing.
The evidence on non-pharmacological management of pain was limited. The interventions and outcomes were varied, and the study sizes were small. There was some evidence of benefit from interventions such as yoga, relaxation massage, mindfulness, CBT and transcutaneous direct current stimulation and hypnosis with neurofeedback. However, the committee agreed that the evidence was insufficient to make any recommendations for or against particular non-pharmacological interventions. The committee therefore made a recommendation for research on non-pharmacological interventions for pain to support future research in this area.
The committee agreed that immobility and problems with posture can often cause or exacerbate pain. It was also acknowledged that spasticity can play a major part in musculoskeletal pain. Therefore, the committee highlighted that musculoskeletal pain should be assessed and treatment offered that is appropriate to and addresses the cause of the pain.
Assessing and investigating the cause of pain is consistent with current best practice. The committee noted that assessment can be done by many different healthcare professionals, such as a rehabilitation physician, a GP, a neurologist, a physiotherapist or an MS nurse. They discussed that this would usually just involve history taking, but for some people further investigations such as scans may be needed. Although there may be costs associated with further investigations, it was agreed that these are likely to be offset by identifying the cause of pain and offering appropriate treatment.
Acknowledging the impact of pain on mental health would not result in a change in practice or significant resource impact.
There was variation in the interventions covered by the studies on non-pharmacological management of cognitive and memory problems, which made it difficult for the committee to come to any conclusions. They agreed that the evidence was too limited to make recommendations about the types of interventions that should be offered. Current practice for treating cognitive impairments in MS varies, so the committee were not able to make consensus-based recommendations on which interventions would be most appropriate based on their experience. They agreed that a new recommendation for research on cognitive rehabilitation should involve larger trials in this area. A recommendation for research on outcome measures for studies of memory and cognition was also made to encourage the use of particular tests or scales for measuring different cognitive functions and improve the ability to pool and interpret data in the future.
Based on their experience, the committee highlighted the need for cognitive symptoms to be assessed as part of the comprehensive review. This assessment is important for people with cognitive symptoms, because their cognitive profile needs to be established before decisions about any interventions can be made, based on their impairments. It was agreed that the type of cognitive assessment needed would differ depending on the person's needs. This might involve a clinical interview with or without carer input or a brief formal neuropsychological assessment. It was noted that a full neuropsychological assessment may be needed in people with a more complex presentation, for example, if fatigue and other disorders may be contributing to cognitive impairments.
In the absence of new evidence, the committee agreed that the previous recommendations on cognition and memory problems should be retained and updated based on their experience and agreed by informal consensus. They agreed that medication should be added to the list of factors that may affect cognition, and that appropriate management of these factors should be offered.
The committee agreed that the recommendation on referral for assessment and management of cognitive impairment should be updated so that referral can be to an occupational therapist, or a neuropsychologist as needed, rather than both, in line with current practice. Referral and the assessment and management of cognitive impairment should be tailored to the person's individual needs, because the cognitive profile of each person is likely to differ.
Cognitive assessment is usually available if the person has been offered a referral, although there may be some regional differences. It was noted that a simple assessment takes 10 to 15 minutes and does not need specific expertise. This type of assessment may be a change in practice for some services, but it is unlikely to have a significant resource impact. A full, longer neuropsychological assessment is a more costly assessment. However, it was noted that only a very small proportion of people are likely to need this longer assessment and future assessments are not as resource intensive as the baseline assessment. Given that only a small number of people would need this more expensive assessment (fewer than 1% of the MS population) and that it may already be current practice for some services, it was not thought to represent a significant resource impact.
Many people with MS already have access to an occupational therapist who is skilled in cognitive assessment and interventions. A proportion will also have access to a neuropsychologist.
There was a lack of evidence for pharmacological management of ataxia and tremor in people with MS. Only 1 new study was identified, which compared botulinum toxin with a placebo. This study was analysed alongside a similar study included in the previous guideline, but the committee agreed that this evidence was insufficient to make recommendations for or against its use. Botulinum toxin is not generally used in current practice for ataxia and tremor, and this use is off label. A recommendation for research on the pharmacological management of ataxia and tremor was developed to support future research in this area.