Clinical Review: Motor neurone disease

Motor neurone disease (MND) is a devastating illness causing progressive muscle paralysis due to degeneration of motor neurones, leading to death, on average, two to three years after the onset of symptoms.

Wasting in muscles of the hands is typical in MND affecting the arms
Wasting in muscles of the hands is typical in MND affecting the arms

Section 1: Epidemiology and aetiology

The lifetime incidence of MND is one in 400 and the short survival time means there are only approximately 5,000 patients with MND in the UK at any one time.1 A small number of atypical cases have a longer chronic course, which can last decades.

Factors contributing to the development of MND include genetic and environmental factors and there is a recognised overlap between MND and other neurodegenerative diseases in patients and their families.

Approximately 10% of patients with MND have frontotemporal dysfunction, and a smaller number have Parkinsonism.

Less than 10% of patients have a family history of MND, with 70% of those having an identifiable genetic cause.2

Forty per cent of familial cases of MND are associated with a recently discovered variable length hexonucleotide repeat expansion in the C9ORF72 gene and families carrying this are more likely to develop other neurodegenerative diseases together with, or in the absence of, MND.3,4

Classification
MND can affect upper and lower motor neurones. Upper motor neurone degeneration causes stiffness and spasticity, weakness, speech and swallowing difficulties, and emotional lability. Lower motor neurone degeneration causes wasting, fasciculations and weakness. Death is usually due to respiratory failure.

Most patients with MND have amyotrophic lateral sclerosis (ALS). They develop upper and lower motor neurone degeneration and have an average life expectancy of two to three years. However, individual prognosis is highly variable and can range from weeks to decades, with 5% surviving more than 10 years.

Patients with primary lateral sclerosis (PLS) have predominantly upper motor neurone dysfunction, while those with primary muscular atrophy (PMA) have lower motor problems. These patients tend to progress more slowly, but there is much overlap and many eventually develop typical ALS.

Section 2 Making the diagnosis

MND is predominantly a disease of the older adult, with peak incidence in the 70s and 80s, but it can affect adults of any age.1

The symptoms can be subtle at first, with an absence of signs and limited to a single area of the body, and may require close observation over months to detect changes.

The RCGP (www.rcgp.org.uk) and the MND Association (www.mndassociation.org) have produced a Red Flags toolkit diagnostic tool and e-learning site for GPs, highlighting signs which should alert doctors to the early presence of MND.

MND is a clinical diagnosis and investigations are used to exclude alternative causes, but neurophysiological tests can support the diagnosis in the absence of a large number of clinical signs.

Several conditions may mimic MND. Isolated fasciculations in the absence of other symptoms or signs are likely to be due to benign cramp fasciculation syndrome.

Primary progressive multiple sclerosis or cervical myelopathy can present with purely upper motor neurone features, or in the case of a myeloneuropathy, may have lower motor neurone features if nerve roots are affected.

Box 1: Red flags for possible MND

Section 3 Managing the condition

The establishment of specialist multidisciplinary teams has significantly improved patients' survival and quality of life.5 Each team should include speech, occupational and physiotherapists, with specialist doctors; ideally, each patient should have a named care co-ordinator.

Prolonging survival
Riluzole, the only drug that improves survival (by an average three months),6 is usually well tolerated. Mild side-effects (GI upset and fatigue) tend to resolve with time.

Significant abnormalities in liver function are uncommon, with regular liver function and blood count monitoring recommended three monthly after initiation.

Use of hepatic enzyme inducers and inhibitors should be avoided, but most common antibiotics and analgesics can be used safely.

Non-invasive ventilation (NIV) improves survival with sustained quality of life in patients who have respiratory failure.7

Patients usually find symptoms of fatigue, sleepiness and poor appetite substantially improved.

Patients may become dependent on NIV, but nasal or full-face masks allow eating and communication, and lightweight batteries are available for travel.

Poor nutrition is associated with poorer outcomes.8 Oral intake may be affected by limb weakness, poor swallowing and fatigue. Early involvement of a speech therapist and a dietitian can prevent weight loss, but insertion of a gastrostomy feeding tube is recommended early in the disease course.

Symptom management
Timely symptom management, with support to overcome disability, is an important role for the multidisciplinary team and the GP. For painful cramps and spasms, quinine, gabapentin and baclofen should be combined with physiotherapy and assessment for exacerbating factors, such as constipation, pain or infection.

Neck weakness can cause head and shoulder girdle ache. A supportive collar and seating may help. Arm weakness can cause a frozen shoulder, which should be treated with physiotherapy and analgesia.

Hyoscine patches reduce excessive saliva. Atropine eyedrops placed under the tongue, glycopyrrolate and amitriptyline are also effective.

Botulinum toxin injected into the salivary glands reduces saliva, but has a small risk of worsening swallowing. Artificial saliva lubricates the mouth. Carbocysteine thins secretions.

Physiotherapy, nebulised saline, suction and cough augmentation machines help expectoration.

NIV may be helpful in managing dyspnoea. Laryngospasm can be precipitated by respiratory secretions or acid reflux. Sublingual lorazepam can be helpful. The use of drugs such as benzodiazepines and opiates can be very effective.

Constipation and urinary urgency, worsened by poor mobility, are treated on the same principles as other diseases. Fertility and sexual function are not affected.

Fatigue is often out of proportion with disability. No medications are particularly helpful, but patients need support to adapt their lifestyle.

Low-dose citalopram or amitriptyline are usually extremely effective in treating emotional lability. Depression and anxiety are treated with standard approaches.

Many patients have mild behavioural or cognitive difficulties and it is helpful for families to recognise that they are due to the MND, rather than the individual.

Section 4 Prognosis

It is impossible to predict prognosis as cases vary so widely, but features suggesting a worse outcome are:

  • Older patients
  • Bulbar or respiratory onset
  • ALS patients are likely to progress faster than PLS or PMA
  • Short time between symptom onset and diagnosis
  • Rapid disease progress

Patients should be given the opportunity to devise an advance directive and have access to palliative care.

Opportunities to introduce these topics may be when considering NIV or feeding tubes, at the emergence of distressing symptoms, or in response to questions about prognosis.

Anxiety and fear can be alleviated by ensuring adequate symptom control, facilitating communication, treating depression and effective care planning.

Medication that can be given by carers can be reassuring. NIV can help with dyspnoea, although some patients opt to withdraw from it at the end of their life.

Breathlessness, anxiety and excessive saliva can be managed using syringe drivers; most MND patients will die peacefully in their sleep.

The role of the GP
Consider MND in patients complaining of painless, progressive stiffness, weakness or speech change, particularly asymmetrical symptoms or where more than one part of the body is involved. Signs of MND might be subtle in early disease.

Look for wasting, fasciculations or brisk reflexes. Signs of respiratory failure include changes in breathing, poor sleep and low appetite.

GPs can prescribe standard medication for pain, secretions and depression. In most cases, MND is not due to lifestyle and is unlikely to be passed on to family members.

Section 5 Case study

A 68-year-old man notices his left leg is dragging after long walks. Examination reveals slight stiffness in his knee and easily elicited reflexes.

His GP reviews him three months later, finding slight thinning of the left quadriceps and brisk reflexes in the arms and legs. Recognising a mild but progressive, asymmetrical weakness as a sign of possible MND, the GP refers the patient to a neurologist, who confirms the diagnosis.

The patient is introduced to the community MND team and the local MND Association. After a year, he requires a wheelchair and adaptations have been made to his house.

After two years, he reports poor sleep and early morning headaches, and his GP alerts the MND nurse. The patient starts NIV, with great improvement in his symptoms. He is referred to the local hospice and draws up an advance directive.

Six months later, he starts to lose weight and is struggling to finish meals. He becomes tearful, anxious and withdrawn. His GP establishes that he is frightened of choking and being unable to swallow or talk.

After discussions with his MND team, he has a gastrostomy, but continues to eat socially, and he is given an iPad with a communication app.

His GP starts him on an antidepressant, and his advance directive is reviewed. He is prescribed sublingual lorazepam and oral morphine (via his gastrostomy).

He develops excessive saliva and secretions, requiring suction and a hyoscine patch, and becomes dependent on NIV. Regular visits from the GP and the hospice team, with guidance from the MND team, allow his symptoms to be well controlled.

He eventually dies in his sleep three years after diagnosis and his family are supported by their GP and the local MND Association.

Section 6 Evidence base

Clinical trials

  • Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) (Review). Cochrane Summaries 2013; 1-38

A meta-analysis of trials from 974 riluzole-treated patients and 503 placebo-treated patients found that riluzole increased median survival by three months. Other potential neuroprotectors, such as lithium, vitamin E and dexpramipexole, have not been shown to be effective.9,10

  • Bourke SC, Tomlinson M, Williams TL et al. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial. Lancet Neurol 2006; 5(2): 140-7

This trial of 41 patients found that NIV in patients with respiratory failure improved survival by approximately seven months and maintained quality of life. NICE has published guidance on the use of NIV in patients with MND.11

Support groups

  • The MND Association (www.mndassociation.org) provides support for patients, families and professionals.

GP education

  • www.mndassociation.org/forprofessionals/Information+for+GPs/

This MND Association website provides information on the role of the GP, links to online learning modules and an extensive reading list.

The RCGP and the MND Association have produced an e-learning module for GPs, which covers the red flag signs of MND, management and end of life care.

Designed by patients and families at the Sheffield MND Care Centre, this website explains the use of NIV.

  • Contributed by Dr Esther Hobson, National Institute for Health Research doctoral research fellow and specialty registrar in neurology, and Dr Christopher McDermott, reader in neurology and co-director, Sheffield Motor Neurone Disease Care and Research Centre.

Click here to take a test on this article and claim a certificate on MIMS Learning

References

1. Alonso A, Logroscino G, Jick SS et al. Eur J Neurol 2009; 16(6): 745-51.

2. Renton AE, Chio A, Traynor BJ. Nat Neurosci 2014; 17(1): 17-23.

3. Renton AE, Majounie E, Waite A et al. Neuron 2011; 72(2): 257-68.

4. DeJesus-Hernandez M, Mackenzie IR, Boeve BF et al. Neuron 2011; 72(2): 245-56.

5. Aridegbe T, Kandler R, Walters SJ et al. Amyotroph Lateral Scler Frontotemporal Degener 2013; 14(1): 13-19.

6. Miller RG, Mitchell JD, Moore DH. Cochrane Summaries 2013; 1-38.

7. Bourke SC, Tomlinson M, Williams TL et al. Lancet Neurol 2006; 5(2): 140-7.

8. Marin B, Desport JC, Kajeu P et al. J Neurol, Neurosurg Psychiatry 2011; 82(6): 628-34.

9. EFNS Task Force on Diagnosis and Management of Amyotrophic Lateral Sclerosis; Andersen PM, Abrahams S, Borasio GD et al. Eur J Neurol 2012; 19(3): 360-75.

10. Cudkowicz ME, Van den Berg JP, Shefner JM et al. Lancet Neurol 2013; 12(11): 1059-67.

11. NICE. CG105. London, NICE, July 2010.

CPD IMPACT: EARN MORE CREDITS

These further action points may allow you to earn more credits by increasing the time spent and the impact achieved.

  • Audit patients who have been diagnosed with MND in the past five years. How did they present and what can be learned?
  • Ask your local consultant neurologist to give a talk about how GPs can improve their diagnostic skills in MND, including recognising the red flags.
  • Review the support your practice offers to patients with MND.

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