Multiple Sclerosis Care and Management
Author
Nikki Embrey, Clinical nurse specialist (multiple sclerosis), North Midland MS Service, University Hospital of North Staffordshire, Stoke on Trent.
Short description
Discover how to manage patients with a complex neurological condition such as multiple sclerosis. This module focuses on self-management and drug therapy including oral disease-modifying therapies.
Detailed description
This learning module describes the complex neurological condition multiple sclerosis (MS) and its management. It outlines the pathophysiology and symptoms, the importance of timely access to specialist services for treatment of symptoms, and relapse and disease management. New and emerging therapies for the management of MS, the role of the multidisciplinary team, the importance of holistic assessment and the role of the MS specialist nurse are discussed. Self-management of MS is integral to managing this life-limiting long-term condition. While there is no cure for MS, new and oral disease-modifying therapies providing better efficacy in stabilising the disease have recently been introduced, reducing relapse frequency and disease activity, and delaying the progression of disability.
Module overview
This module describes the complex neurological condition multiple sclerosis (MS) and its management. It outlines the pathophysiology and symptoms, the importance of timely access to specialist services for treatment of symptoms, and relapse and disease management. New and emerging therapies for the management of MS, the role of the multidisciplinary team, the importance of holistic assessment and the role of the MS specialist nurse are discussed. Self-management of MS is integral to managing this life-limiting long-term condition. While there is no cure for MS, new and oral disease-modifying therapies providing better efficacy in stabilising the disease have recently been introduced, reducing relapse frequency and disease activity, and delaying the progression of disability.
Keywords
central nervous system, MS, multiple sclerosis, nervous system diseases, neurology, patient-centred care, self-care, self-management.
Aims
This module aims to improve nurses’ knowledge of the management of multiple sclerosis (MS), a complex neurological condition.
Intended learning outcomes
After reading this module and completing the time out activities you should be able to:
Explain the pathophysiology of MS.
Discuss the signs, symptoms and management of MS.
Describe the treatment options available.
Promote self-management of the condition and multidisciplinary working.
Introduction
In 2010, an estimated 126,669 people in the UK had MS, with 6,003 new cases diagnosed in the same year (Mackenzie et al 2014). This study recognised an increasing population of people who are living longer with MS and the implications this has for MS services.
Definition
Multiple sclerosis (MS) is a common chronic neurological condition causing disability in young adults (MacLurg et al 2005). It is a central nervous system (CNS) disorder involving the brain and spinal cord, demyelination of nerves and impairment of nerve conduction.
MS often affects those aged 20-40 and affects three times more women than men. The condition is occasionally diagnosed in young children and those over 65. There are varying courses of the condition, the most common being acute, inflammatory episodes (relapses), followed by periods of remission. However, this is often superimposed on a background of progressive disability, reduced functionality and neurological impairment. MS may exist subclinically. The trigger for the initial symptoms and how the condition develops are not understood fully. MS symptoms are variable, and the disease is unpredictable; for some, life expectancy is unaffected, while others may experience years of disability or early death.
While the cause of MS is still not known, and a cure has not been found, the management of MS has improved significantly. Since the introduction of disease-modifying treatments (DMTs) – under the risk-sharing scheme (Department of Health (DH) 2002) – there has been an increase in MS services, in particular access to specialist nurses and an increasing understanding and responsiveness towards patient management. Revised National Institute for Health and Care Excellence (NICE) (2014a) MS guidelines have been published.
Learning Points
- Multiple sclerosis (MS) is a common chronic neurological condition causing disability in young adults. It is a central nervous system disorder involving the brain and spinal cord, demyelination of nerves and impairment of nerve conduction.
- There are varying courses of the condition, the most common being acute, inflammatory episodes (relapses), followed by periods of remission. However, this is often superimposed on a background of progressive disability, reduced functionality and neurological impairment.
- MS symptoms are variable, and the disease is unpredictable; for some, life expectancy is unaffected, while others may experience years of disability or early death.
Pathophysiology
MS is a complex condition (Dutta and Trapp 2006). It is an inflammatory, demyelinating disease of the white matter of the CNS that develops in a genetically susceptible individual after exposure to non-specific environmental factors (MS Trust 2011). Mechanisms for breakdown of the blood-brain barrier (BBB) are incompletely understood in MS, although immune cells are thought to infiltrate the brain, leading to inflammation and demyelination (Minagar and Alexander 2003). Following myelin breakdown (Figure 1), axonal and glial injury, nerve conduction is blocked, resulting in nerve pathways malfunctioning (Goodkin et al 1998). Frequent relapses lead to an overgrowth of astrocytes, which results in scarring (plaques) (Zajicek et al 2007).
Figure 1. Structure of neurones
Magnetic resonance imaging (MRI) studies suggest subtle focal tissue alterations may precede the appearance of an active MS plaque (Figure 2) (Lassmann et al 2007). Lesions appear mainly in a periventricular distribution, with clusters around the ventricles, but the cortex can also be affected, with diffuse injury of the normal-appearing white matter (Lassmann et al 2007). Oligodendrocyte destruction also results in loss of the myelin sheath, which leads to the variable symptoms of MS, depending on the areas affected.
Figure 2. Magnetic resonance imaging scan of a female with multiple sclerosis
Complete time out activity 1
Consider the process of demyelination and the cells responsible for creating myelin that are targeted in MS. What is the function of myelin and the effect of its breakdown on an individual?
Cause
The cause of MS remains unknown; however, the evidence points towards a complex interaction with genetic and environmental factors. These are thought to provoke the immune system to produce an autoimmune response, which attacks the cells that form myelin. With time, axonal loss and neurodegeneration lead to accumulative disability. Degeneration is thought to begin early in the subclinical phase. Various factors may influence progression, such as (MS Trust 2011):
- Familial risk.
- Gender.
- Diet.
- Levels of vitamin D3 and ultraviolet-B (UVB) exposure.
- Month and place of birth.
- Smoking.
- Migration.
- Epstein-Barr serology.
Learning Points
- MS is an inflammatory, demyelinating disease of the white matter of the CNS that develops in a genetically susceptible individual after exposure to non-specific environmental factors.
- Frequent relapses lead to an overgrowth of astrocytes, which results in scarring (plaques).
- Lesions appear mainly in a periventricular distribution, with clusters around the ventricles, but the cortex can also be affected, with diffuse injury of the normal-appearing white matter.
- Various factors may influence progression, such as familial risk, gender, diet, levels of vitamin D3 and ultraviolet-B (UVB) exposure, month and place of birth, smoking, migration and Epstein-Barr serology.
Diagnosis
Diagnosis is made by a neurologist, however a team of specialist healthcare professionals, including nurses, will be involved. Common initial symptoms of MS include:
- Visual disturbances such as pain in and around the eyes, blurred vision and altered colour perception, as a result of optic nerve inflammation.
- Sensory disturbances such as numbness, paraesthesia or weakness, as a result of inflammation along the spine (transverse myelitis).
- Balance problems, vertigo and diplopia, as a result of brainstem or cerebellar inflammation.
MRI techniques
Neurologists undertake a detailed history and neurological examination, gather evidence of previous episodes or neurological damage, and request investigations such as MRI to help support a clinical diagnosis of MS.
Table 1 lists the different MRI techniques used. T1-weighted images show hypo-intensities indicating areas of permanent nerve damage. T1 images enhanced with gadolinium contrast show current disease activity where the BBB is disrupted and show active inflammation – areas of new or enlarging lesions. T2-weighted images indicate the disease burden of lesions – the load of old and new lesions.
Table 1. Magnetic resonance imaging techniques used in diagnosis
| T1-weighted images | T2-weighted images | Gadolinium-enhanced images |
| Provide better correlation between disability and black holes of irreversible axonal loss. | Reveal inflammatory lesions – demyelination, gliosis, axonal loss, new or active and old lesions, remyelination, and overall burden of disease. | Highlight blood-brain barrier disruption; enhancing the images will reveal lesions that are currently active or inflammatory. |
Complete time out activity 2
Consider the findings on an MRI scan that might suggest a person with MS is in the early stage of demyelination and compare them with the findings on an MRIof someone with more advanced demyelination.
Lumbar puncture and analysis
A lumbar puncture and analysis of cerebrospinal fluid (CSF) can provide supporting evidence of a diagnosis of MS. A positive result is usually indicated by elevated levels of immunoglobulin G antibodies, protein, and oligoclonal bands – which indicate the breakdown of myelin – in the CSF and not present in the serum sample taken at the same time.
Table 2. McDonald criteria for diagnosis of multiple sclerosis (revised 2010)
| Attacks | Lesions | Additional criteria for diagnosis |
| 2 attacks or more | 2 lesions or more | None. Clinical evidence alone will suffice. |
| 2 attacks or more | 1 lesion | Dissemination in space on magnetic resonance imaging (MRI), or await further clinical attack implicating a different central nervous system (CNS) site. |
| 1 attack | 2 lesions | Dissemination in time on MRI, or await further clinical attack implicating a different CNS site. |
| 1 attack | 1 lesion | Dissemination in space and time on MRI, or await further clinical attack implicating a different CNS site. |
| 0 attack (progression from onset) | One year of disease progression (retrospective or prospective) and at least two out of three criteria:
|
Complete time out activity 3
A patient newly diagnosed with MS asks you about the condition. Think about how you would respond in a way that the patient understands.
Suggested reading:
- Multiple Sclerosis Trust (2011) Multiple Sclerosis Information for Health and Social Care Professionals. www.mstrust.org.uk/downloads/ms-info-health-professionals.pdf
- MS Society information – What is MS? tinyurl.com/k258cte
- Causes of MS www.mssociety.org.uk/what-is-ms/information-about-ms/causes
Complete time out activity 4
Which of the following is most suggestive of a clinical diagnosis of MS and why?
- Two occurrences of optic neuritis one year apart.
- Progressive weakness of the legs over one year.
- Temporary loss of feeling in the hands, which occurs again six months later.
- An episode of optic neuritis, followed six months later by right arm weakness.
Learning Points
- Common initial symptoms of MS are visual disturbances (pain in and around the eyes, blurred vision and altered colour perception), sensory disturbances (numbness, paraesthesia or weakness) and balance problems (vertigo and diplopia).
- The different MRI techniques used to diagnose MS are T1-weighted images, T2-weighted images and gadolinium-enhanced images.
- T1-weighted images show hypo-intensities indicating areas of permanent nerve damage, T1 images enhanced with gadolinium contrast highlights the current disease activity where the BBB is disrupted and T2-weighted images indicate the disease burden of lesions.
- A lumbar puncture and analysis of cerebrospinal fluid (CSF) can provide supporting evidence of a diagnosis of MS. Other tests include neurophysiological tests, visual evoked potentials, and measuring the speed of impulses from the cortex along the optic pathways.
Management
MS nurses co-ordinate patient care from diagnosis; general nurses also care for people with MS in primary and secondary care settings. Management of patients with MS follows three pathways:
- Symptom management.
- Relapse management.
- Disease management using DMTs.
Symptom management
Optic neuritis
The most common symptom of MS involving visual pathways is optic neuritis, which presents as acute, unilateral eye pain, accentuated by ocular movements, followed by variable visual loss (scotoma) of mainly central vision. It is rare for bilateral simultaneous optic neuritis to occur in MS. If optic neuritis occurs bilaterally, the impairment is asymmetrical, and usually more severe in one eye. More often, the lesion of the optic nerve is retrobulbar (the area of inflammation is between the back of the eye and the brain). As well as visual acuity and pain, the patient may present with desaturation of colour.
Treatment: high-dose steroids (see section on relapse).
Internuclear ophthalmoplegia
Internuclear ophthalmoplegia refers to abnormal horizontal ocular movements, with lost or delayed adduction and horizontal nystagmus of the abducting eye, and is caused by a lesion in the brainstem. When present bilaterally, it is usually coupled with vertical nystagmus on upwards gaze. A bilateral internuclear ophthalmoplegia is most suggestive of MS. Nystagmus is characterised by rapid, small-amplitude, pendular oscillations of the eyes in the primary position. Patients frequently complain of oscillopsia – oscillation of objects in the field of vision, which impairs visual performance.
Treatment: high-dose steroids.
Neuropathic pain
Sensory symptoms occur in almost all patients during the course of the disease, reflecting spinothalamic or posterior column lesions, and are variable. Examination shows disruption to the sense of vibration, pin-prick, hot and cold, or joint position. Pain can be persistent or paroxysmal, often having an effect on quality of life, and its management is complex.
Assessment of pain is important and involving a pain specialist to manage the patient’s pain is indicated in some cases.
- Primary pain is a direct result of nerve damage.
- Secondary or nociceptive pain is a consequence of musculoskeletal problems, and is often related to posture complications.
- Neuropathic pain manifests as dysaesthesia or paraesthesia.
Treatment: a choice of amitriptyline, duloxetine, gabapentin or pregabalin is recommended as initial treatment for neuropathic pain (NICE 2013). If the initial treatment is not effective or not tolerated, one of the other three drugs should be offered, and then switched again if the second and third drugs are not effective or not tolerated. Capsaicin cream should be considered for localised neuropathic pain if the patient is avoiding or unable to tolerate oral treatments (NICE 2013). Cannabis sativa extract, capsaicin patch, lacosamide, lamotrigine, levetiracetam, morphine, oxcarbazepine, topiramate, tramadol (long-term use) and venlafaxine should not be used unless advised by a specialist.
Pain specialists, neurosurgeons and the multidisciplinary team, including neuro-psychologists, may need to be involved in the management of pain in MS. Pharmacological and non-pharmacological treatments including complementary and alternative treatments have been extensively reviewed in the recent MS guidelines (NICE 2014a).
Paraparesis or paraplegia
Paraparesis, or paraplegia, occurs as a result of lesions in the descending motor tracts of the spinal cord. Spasticity is common with extensor spasms of the legs and sometimes the trunk. Neurological examination may show exaggerated deep tendon reflexes, sustained clonus or extensor plantar responses. Paraparesis is caused by damage to the upper motor neurones, accompanied by lower-limb weakness, and may be exaggerated by infection, constipation and other problems.
Treatment: a multidisciplinary team approach, including physiotherapy and occupational therapy, is advocated. MS guidelines indicate baclofen and gabapentin to be used as first-line treatment options; tizanidine and dantrolene to be used as second-line treatment options; and benzodiazepines as third-line options (NICE 2014a). Nabiximols or fampridine are not recommended but intrathecal baclofen was found to result in inhibition of spinal reflexes, reducing spasms, clonus and pain (NICE 2014a).
Uhthoff’s phenomenon
Definition
Uhthoff’s phenomenon occurs with a rise in body temperature, causing slowed nerve conduction and increased neurological symptoms, from visual (sensory) disturbance to central motor function loss (Humm et al 2004).
Treatment: nurses can provide advice on using cooling suits, avoiding hot climates and keeping hydrated.
Co-ordination and movement
Attacks of motor or sensory phenomena (paroxysmal symptoms) can occur as a result of demyelinating lesions. Lesions within the brainstem may cause paroxysmal diplopia, facial paraesthesia, trigeminal neuralgia, ataxia, and dysarthria. Motor system involvement results in painful tonic contractions of muscles.
Co-ordination is affected if there is demyelination to cerebellar pathways affecting gait, standing and sitting balance, causing intention tremor and ataxia. Examination typically reveals dysmetria and dysdiadochokinesia. Intention tremor (action tremor) can affect the upper body, head, walking and sitting balance, and trunk. Cerebellar signs are usually mixed with pyramidal (corticospinal) tract signs. Tremor affects 25-60% of patients, can be severely disabling and embarrassing for patients, and is difficult to manage (Koch et al2007).
Lhermitte’s phenomenon is a sudden transient sensory shock-like symptom radiating down the spine triggered by flexing the head forward, as a result of posterior column involvement. Trigeminal neuralgia is more common in people with MS than the general population (Zvartau-Hind et al 2000).
Treatment: various pharmacological and non-pharmacological treatments were discussed by Koch et al (2007), including gabapentin, but cannabinoids appearineffective. It was found to be important to involve the multidisciplinary team, particularly physiotherapy and orthotics, and limb cooling achieved functional improvement. Tremor reduction using stereotactic thalamotomy or stimulation guidance is outlined in Interventional Procedure Guidance No. 188 (NICE 2006). Initial treatment of trigeminal neuralgia is carbamazepine, with specialist referral for further treatment (NICE 2013).
Bowel, bladder and sexual dysfunction
Bowel, bladder and sexual dysfunction are common in patients with MS. Urinary urgency and/or frequency should be treated with anticholinergic (antimuscarinic) medications if a post-void assessment is normal (NICE 2012), and continence nurse advisers should be consulted. Urinary tract infections are common and may increase the extent of bladder dysfunction. Further information can be found in the UK consensus on bladder management (Fowler et al 2009).
Constipation is common, and faecal incontinence is rare. Contributory factors include lack of exercise; poor diet and fluid intake; medications; decreased rectal sensation; and sphincter dysfunction. Sexual dysfunction is reported in men with erectile dysfunction and women with reduced vaginal sensation; and fatigue and medications can also affect libido.
Treatment: assessment of bowel, bladder and sexual dysfunction is vital in the clinical setting to provide optimal care and advice, and assess the effects symptoms may have on relationships. Ward (2005) provided practical suggestions for the management of sexual dysfunction, recognising the importance of the nurse’s role in raising such issues with patients and providing education and support.
Fatigue
Fatigue is the most common symptom experienced by people living with MS. In a survey of 2,265 people with MS, 88% reported moderate to high levels of fatigue, which had an effect on activities of daily living (Hemmett et al 2004). Disrupted sleep as a result of pain, spasms, irritable legs, bladder overactivity and medications is a contributory factor. There appears to be a correlation between fatigue and disturbed sleep in MS patients.
Treatment: self-management strategies support patients to manage disabling symptoms by understanding underlying causes, exercising, and conserving energy. Amantadine is recommended by NICE (2014a), as are ‘mindfulness’ training, cognitive behavioural therapy (CBT) and fatigue management programmes.
Mental health
At least half of people with MS experience depression, and a quarter have anxiety disorders (Siegert and Abernethy 2005). It is not known whether depression in MS patients reflects a comorbid association with bipolar illness, or is an effect of frontal or subcortical white matter disease (Korostil and Feinstein 2007).
Treatment: several approaches may be taken to treat depression, including self-help, counselling, interpersonal therapies, talking therapies, CBT, pharmacological therapies, use of antidepressants, or a combination of therapies (NICE 2009).
The rate of suicide in people with MS was 7.5 times higher than for the age-matched general population (Sadovnick et al 1991).
Cognitive impairment
Formal psychometric testing shows approximately half of all people with MS experience some inefficiency in concentration or other mental tasks (MS Trust 2011), and cognitive impairment may be present early in the condition. Frequent abnormalities relate to abstract conceptualisation, short-term memory, attention, and speed of information processing.
Treatment: psychological assessment of underlying problems may help, however treatment proves difficult.
Complete time out activity 5
Think about the silent or hidden symptoms associated with MS and the difficulties they present for the individual. Access the NICE (2014a) guidelines to confirm options for symptom management.
Learning Points
- Management of patients with MS follows three pathways such as symptom management, relapse management and disease management using DMTs.
- The most common symptom of MS involving visual pathways is optic neuritis, which presents as acute, unilateral eye pain, accentuated by ocular movements, followed by variable visual loss (scotoma) of mainly central vision. If optic neuritis occurs bilaterally, the impairment is asymmetrical, and usually more severe in one eye.
- Fatigue is the most common symptom experienced by people living with MS. There appears to be a correlation between fatigue and disturbed sleep in MS patients.
- At least half of people with MS experience depression, and a quarter have anxiety disorders. Several approaches may be taken to treat depression, including self-help, counselling, interpersonal therapies, talking therapies, CBT, pharmacological therapies, use of antidepressants, or a combination of therapies
Relapse management
Confavreux et al (2000) defined MS relapse as occurrence or re-occurrence of worsening symptoms of neurological dysfunction, lasting more than 24 hours, stabilising and/or resolving either partially or completely, and not fatigue or fever-related. Symptoms occurring within one month after the initial symptoms were considered part of the same relapse. Relapses are also called attacks, episodes, flare-ups and acute exacerbations. Infection should always be excluded as a possible underlying cause for worsening symptoms (pseudo or super-imposed relapse). Relapses are spontaneous events, but may be worsened by stress, anxiety and fatigue. Relapse is rare during pregnancy, especially during the third trimester, but the risk of relapse increases post-partum before returning to the pre-pregnancy rate at three months (Confavreux et al 1998).
High-dose steroids reduce inflammation and speed recovery, but should only be prescribed following assessment (NICE 2014a). The recommended treatment regimen involves methylprednisolone 0.5g orally for five consecutive days (NICE 2014a). However, in severe relapse, those who have not responded to oral glucocorticoids or those who require monitoring with diabetes or mental health problems, intravenous (IV) methylprednisolone 500mg-1g should be administered daily for three to five days (NICE 2014a).
Disease management using disease-modifying treatments
The emergence of DMTs in the 1990s changed the management of MS, and resulted in the development of the MS specialist nurse role and establishment of the risk-sharing scheme to enable access to DMTs for people with MS (DH 2002). The scheme allowed suitably eligible patients, assessed using the Association of British Neurologists (ABN) (2009) guidelines, to be treated using DMTs. Data are being collected from more than 5,000 patients registered in the study, which ends in 2015. This data will provide evidence of benefits and risks of conventional treatment. The ABN guidelines are designed to support and represent a national consensus concerning appropriate use of currently approved therapies.
Interferon beta 1b – the first available licensed DMT for treatment of MS – and interferon beta 1a, reduce the frequency and severity of relapses for patients with relapsing-remitting MS (RRMS) (Box 1); however, some patients continue to have accruing disability. While the body produces several types of interferons (cytokines) naturally, interferon beta 1b and 1a were found to modulate T cell and B cell activity and reduce the permeability of the BBB to inflammatory cells (Dhib-Jalbut and Marks 2010).
Box 1. Types of multiple sclerosis (MS)
- Relapsing remitting MS (RRMS) is characterised by clearly defined relapses with full recovery or with sequelae and residual deficit. This type of MS accounts for approximately 85-90% of MS cases at onset (MS Trust 2011). However, many will eventually enter a secondary progressive phase.
- Secondary progressive MS (SPMS) occurs in around 65% of people with RRMS (MS Trust 2011). SPMS is characterised by an initial relapsing course, followed by progression with or without relapse, minor remissions and plateaus. Some studies suggest SPMS develops in most patients with RRMS, causing greater neurological disability (MS Trust 2011).
- Primary progressive MS is diagnosed in 10-15% of people with MS (MS Trust 2011). This type of MS is characterised by disease progression from initial onset, occasional plateaus and temporary minor improvements. Patients experience a steady decline in function from initial symptoms and never have acute attacks. These patients have a more even sex distribution, tend to have a later age of onset, and may have a worse prognosis for disability compared to patients with RRMS.
- Benign MS may exist, but can only be diagnosed if the patient remains completely able in all functional neurologic systems for at least 15 years after onset. Some patients never experience a second relapse. Although the exact frequency of this benign form of disease is unknown, many will never come to medical attention. Among patients in a population-based cohort study who had MS for ten or more years, about 17% had minimal or no disability (Pittock et al 2004).
- Progressive relapsing MS is characterised by progressive disease from onset, with clear acute relapses, with or without full recovery. Progression continues during periods between disease relapses.
Glatiramer acetate reduced the relapse rate by about one third over two years in patients with RRMS (Johnson et al 1995). The drug is a synthetic combination of four amino acids, resembling myelin basic protein, has a diverse mechanism of action and immune-modulatory and neuro-protective consequences (Aharoni 2013).
Natalizumab is the first licensed treatment given by infusion for highly active RRMS or rapidly evolving severe MS – two or more disabling relapses in one year and one or more gadolinium-enhancing lesions, or a significant increase in T2 lesion load compared with previous MRI. It acts by preventing the migration of immune cells across the BBB, preventing inflammation and the destruction of myelin (Steinman 2005). Natalizumab is the most efficacious MS therapy, reducing relapse by around two thirds, with a 92% reduction in lesions on gadolinium-enhanced MRI, and evidence suggesting it slows progression of disability and improves quality of life (Polman et al 2006). Progressive multifocal leukoencephalopathy is a rare side effect that can cause death or severe disability.
Natalizumab and interferon beta 1a (subcutaneous injection) were shown to be superior to all other conventional treatments for preventing relapses in RRMS in the short term, compared with a placebo, with a moderate protective effect against disability progression (Filippini et al 2013).
Complete time out activity 6
A patient asks for advice on the side effects of natalizumab. Describe how you would provide a response that is positive, realistic and based on research evidence.
Learning Points
- MS relapse is occurrence or re-occurrence of worsening symptoms of neurological dysfunction, lasting more than 24 hours, stabilising and/or resolving either partially or completely, and not fatigue or fever-related. The recommended treatment regimen involves methylprednisolone 0.5g orally for five consecutive days.
- Interferon beta 1b – the first available licensed DMT for treatment of MS – and interferon beta 1a, reduce the frequency and severity of relapses for patients with RRMS; however, some patients continue to have accruing disability.
Oral therapies
Fingolimod was the first licensed, oral, second-line treatment for patients with RRMS where first-line treatment failed. It acts by binding to receptors on the surface of lymphocytes, and has unique immunoregulatory properties, preventing immune cells from exiting the lymphoid tissue and reaching the inflammatory tissue. A 50% reduction in relapse rate was reported (Ingwersen et al 2012). Research suggests fingolimod may stimulate re-myelination (Jackson et al 2011). It is contraindicated in patients with previous immunodeficiency, a risk of opportunistic infections, severe active infections, hepatitis, severe liver impairment, malignancies and hypersensitivities.
Side effects: include a rare bradyarrhythmia, which requires careful monitoring post initiation of treatment for six hours. Fingolimod has not been studied in patients with underlying cardiac problems or those on beta blockers. It causes a significant reduction in lymphocyte count and infections require monitoring.
Teriflunomide is an approved treatment for MS (NICE 2014b) – as an alternative to conventional treatments for patients with active RRMS – and eligible to be used as a first-line therapy (NICE 2014b). It reduced numbers of B cells and T cells, and helps to protect against relapses by limiting the increase in lymphocytes and reducing the inflammation that leads to demyelination. Teriflunomide has immunomodulatory and anti-inflammatory actions and studies show that the relapse rate is reduced by a similar percentage to beta interferons’ relapse rate. It has disability data showing reduction in disability progression.
Side effects: include influenza, infections, paraesthesia, diarrhoea, nausea, elevated liver enzymes (alanine transaminase (ALT)) and hair thinning. Teriflunomide can take eight months to two years to exit the system, and pregnancy is not advised until the drug has been eliminated from the blood; an accelerated elimination procedure is recommended to rapidly achieve a safe plasma concentration level. The drug requires twice-weekly blood monitoring in the initial phase of treatment.
Dimethyl fumarate is an approved therapy for RRMS (NICE 2014c). It reduces inflammation caused by the MS immune response and has neuroprotective properties. One study compared it to a placebo, showing a significant reduction in the relapse rate of 48-53% and a reduction of disability progression of 34-38%. A second study compared it to glatiramer acetate, which showed similar statistically significant results – a 44-51% reduction in relapses and a reduced disability progression of 21-24% – after two years (Gold et al 2012). It decreases the number of new and enhancing lesions on MRI after two years.
Side effects: include flushing, feeling hot, diarrhoea, nausea, abdominal pain and headache. Blood monitoring is similar to that required for interferons.
Alemtuzumab is a novel therapy using annual infusion for three to five days and is recommended for people with active RRMS (NICE 2014d). Alemtuzumab works by binding and destroying white blood cells, preventing immune cells from entering the brain and attacking myelin. The most recent data indicate a significantly reduced relapse rate and a reduction in worsening disability when compared to standard MS therapies.
Side effects: include infusion site reactions, insomnia, fatigue, infections and, less commonly, autoimmune thyroid problems and immune thrombocytopenia.
Future therapies
Future therapies may include laquinimod, an oral immunomodulatory therapy that has undergone phase 3 trials; daclizumab, a monoclonal antibody being compared with beta interferons in phase 3 trials; and ocrelizumab, a monoclonal antibody being studied in patients with primary progressive MS (PPMS).
Stem cells may have the potential to restore lost function in nerve cells as a result of MS, but research is still in the early stages. Cannabis studies have shown evidence of anti-inflammatory properties, promotion of re-myelination and neuroprotection (MS Trust 2011), with the CUPID trial evaluating if tetrahydrocannabinol can slow disability progression in PPMS; tetrahydrocannabinol use in secondary progressive MS has failed to demonstrate effects (Zajicek et al 2013).
Complete time out activity 7
Consider the level of information available to patients to help them make a decision about the use of a particular therapy. What therapy would you recommend to someone diagnosed with RRMS?
Learning Points
- Oral therapies include fingolimod, teriflunomide and dimethyl fumarate.
- Fingolimod acts by binding to receptors on the surface of lymphocytes, and has unique immunoregulatory properties, preventing immune cells from exiting the lymphoid tissue and reaching the inflammatory tissue.
- Teriflunomide is an approved treatment for MS as an alternative to conventional treatments for patients with active RRMS and eligible to be used as a first-line therapy which reduces numbers of B cells and T cells. It helps to protect against relapses by limiting the increase in lymphocytes and reducing the inflammation that leads to demyelination.
- Dimethyl fumarate reduces inflammation caused by the MS immune response and has neuroprotective properties.
- Alemtuzumab works by binding and destroying white blood cells, preventing immune cells from entering the brain and attacking myelin.
- Future therapies may include laquinimod, an oral immunomodulatory therapy that has undergone phase 3 trials; daclizumab, a monoclonal antibody being compared with beta interferons in phase 3 trials; and ocrelizumab, a monoclonal antibody being studied in patients with primary progressive MS.
- Natalizumab is the first licensed treatment given by infusion for highly active RRMS or rapidly evolving severe MS, reducing relapse by around two thirds, with a 92% reduction in lesions on gadolinium-enhanced MRI.
Role of the specialist nurse
MS specialist nurse numbers have increased steadily. Their roles include co-ordinating DMT risk-sharing schemes, collating data and educating patients about realistic treatment expectations.- Newer therapies demand closer monitoring of the patient; side effect profiles are increased; and more treatment options are available, making the care of these patients more complex.
- To ensure concordance with oral therapies, good decision making by the MS nurse is essential (Ward-Abel et al 2014).
- Specialist nurses have an integral role in the management of patients with MS – they add value to patient care while generating efficiencies for organisations through new and innovative ways of working (Royal College of Nursing (RCN) 2010).
Benefits generated by specialist nurses include (RCN 2010):- Reduced waiting times.
- Avoidance of unnecessary hospital admission and/or re-admission.
- Reduced post-operative hospital stay times.
- Freed-up consultant appointments.
- Delivery of community services at the point of need.
- Reduced treatment drop-out rates.
- Provision of education to health and social care professionals.
- Introduction of innovative service delivery frameworks.
- Direct specialist advice given to patients and their families.
Further work is being undertaken to evaluate the MS specialist nurse’s role (Mynors et al 2012). The MS Society and MS Trust support nurses, and have developed strong partnerships to improve care and services for everyone affected by MS.Self-management
Self-management is still a relatively new concept for enabling patients to manage the life-changing diagnosis of MS.Factors important to self-management of MS include (Embrey 2005, 2006):- The patient’s knowledge and skills relating to their condition.
- Confidence to enable action.
- Improved self-efficacy.
- Use of available resources.
- Working in partnership with the multidisciplinary team.
- Skills in problem-solving, setting goals, monitoring and decision making.
Role of a nurse to promote self-management programmes
Nurse specialists readily promote self-management programmes similar to the Expert Patient Programme (DH 2001).- These programmes aim to involve patients in the treatment process and share responsibility for disease management with health and social care professionals, to ensure better control of their quality of life.
- Self-management programmes can be designed to reduce severity of symptoms or improve confidence, resourcefulness and self-efficacy (DH 2001).
- The overall goal of self-management is to help people to help themselves, with the premise that the better their self-management, the better their symptom control and quality of life; however, the focus must be on patient activity rather than on basic education (Barlow et al 2002).
- A nurse’s role, whether on the ward or in the community, is to encourage optimal medication management, increase adherence, and promote persistence, which results in fewer relapses and the ability of patients to manage their own health (Stokl et al 2010).
- Complete time out activity 8Consider the support the MS Society and MS Trust can offer patients and nurses. You may wish to access their websites at: www.mssociety.org.uk and www.mstrust.org.uk
- Learning Points
- Benefits generated by MS specialist nurses include reduced waiting times; avoidance of unnecessary hospital admission and/or re-admission; reduced post-operative hospital stay times; freed-up consultant appointments; delivery of community services at the point of need; reduced treatment drop-out rates; provision of education to health and social care professionals; introduction of innovative service delivery frameworks; and direct specialist advice given to patients and their families.
- Factors important to self-management of MS include the patient’s knowledge and skills relating to their condition; confidence to enable action; improved self-efficacy; use of available resources; working in partnership with the multidisciplinary team; and skills in problem-solving, setting goals, monitoring and decision making.
- The overall goal of self-management is to help people to help themselves, with the premise that the better their self-management, the better their symptom control and quality of life; however, the focus must be on patient activity rather than on basic education.
- A nurse’s role, whether on the ward or in the community, is to encourage optimal medication management, increase adherence, and promote persistence, which results in fewer relapses and the ability of patients to manage their own health.
Conclusions
- While there is still much to learn about MS, treatments have improved significantly. In particular, treatments for those with RRMSappear to improve relapse rates, reduce disease activity and delay progression.
- The nurse’s role in providing individuals with the support, resources and education to help them self-manage their condition is pivotal to effective management of this condition.
- All members of the multidisciplinary team have a role in supporting those affected by MS. This includes supporting healthcare professionals to provide optimum care, signposting patients to quality services and enabling them to live independently.
- In a time of developments in treatment options for MS, nurses will be pivotal in supporting decision making in the future and in educating patients, carers and healthcare professionals.
Acronyms
ABN: Association of British NeurologistsALT: alanine transaminaseBBB: blood-brain barrierCBT: cognitive behavioural therapiesCNS: central nervous systemCSF: cerebrospinal fluidCUPID: cannabinoid use in progressive inflammatory brain diseaseDH: Department of HealthDMTs: disease-modifying treatmentsIV: intravenousMRI: magnetic resonance imagingMS: multiple sclerosisNICE: National Institute for Health and Care ExcellencePML: progressive multifocal leukoencephalopathyPPMS: primary progressive MSRCN: Royal College of NursingRRMS: relapsing-remitting MSSPMS: secondary progressive MSUVB: ultraviolet-BGlossary
Ataxia: an impaired ability to co-ordinate movement, often characterised by a staggering gait and postural imbalance.CUPID trial: CUPID was a research trial looking at whether tetrahydrocannabinol (THC), one of the active ingredients in cannabis, could slow the rate of increasing disability in people with progressive multiple sclerosis.Demyelination: the process of destruction or removal of the myelin sheath from a nerve or nerve fibre.Diplopia: double vision caused by defective function of the extraocular muscles or a disorder of the nerves that innervate the muscles.Dysaesthesia: a common effect of spinal cord injury, which is characterised by sensations of tingling, numbness or pain below the level of the lesion.Dysarthria: difficult, poorly articulated speech, resulting from interference in the control and execution over the muscles of speech usually caused by damage to a central or peripheral motor nerve.Dysdiadochokinesia: an inability to preform rapidly alternating movements, such as rhythmically tapping the fingers on the knee.Dysmetria: an abnormal condition that prevents the affected individual from properly measuring distances associated with muscular acts and from controlling muscular action.Lhermitte’s phenomenon: a sudden transient sensory shock-like symptom radiating down the spine triggered by flexing the head forward, as a result of posterior column involvement.Multiple sclerosis (MS): a central nervous system disorder involving the brain and spinal cord, demyelination of nerves and impairment of nerve conduction.Nystagmus: involuntary, rhythmic movement of the eyes. Oscillations may be horizontal, vertical, rotary or mixed.Ophthalmoplegia: an abnormal condition characterised by paralysis of the motor nerves of the eye.Optic neuritis: inflammation, degeneration, or demyelination of the optic nerve or optic disc caused by a wide variety of diseases.Paraparesis: a partial paralysis, usually affecting only the lower extremities. It is caused by damage to the upper motor neurones, accompanied by lower-limb weakness, and may be exaggerated by infection, constipation and other problems.Paresthesia: an abnormal sensation, typically experienced as numbness, tingling, or ‘pins and needles’. Caused chiefly by pressure on or damage to the peripheral nerves.Progressive multifocal leukoencephalopathy: a rare and usually fatal viral disease characterised by progressive damage or inflammation of the white matter of the brain at multiple locations.MS relapse: the occurrence or re-occurrence of worsening symptoms of neurological dysfunction, lasting more than 24 hours, stabilising and/or resolving either partially or completely, and not fatigue or fever-related. Also called attacks, episodes, flare-ups and acute exacerbations.Scotoma: a defect of vision in a defined area of the visual field in one or both eyes.Transverse myelitis: an acute episode of spinal cord inflammation involving both sides of the cord.Trigeminal neuralgia: a neurological condition of the trigeminal facial nerve, characterised by paroxysms of flashing, stab-like pain radiating along the course of a branch of nerve from the angle of the jaw.Uhthoff’s phenomenon: occurs with a rise in body temperature, causing slowed nerve conduction and increased neurological symptoms, from visual (sensory) disturbance to central motor function loss.Vertigo: a sensation of instability, giddiness, loss of equilibrium, or rotation, caused by a disturbance in the semicircular canal of the inner ear or the vestibular nuclei of the brainstem.References
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