Clinical Review - Motor neurone disease

Contributed by Dr Clare Wood-Allum, lecturer in neurology and honorary registrar, and Dr Christopher McDermott, lecturer and consultant neurologist for University of Sheffield and Sheffield Teaching Hospitals NHS Trust.

Non-invasive ventilation of a patient with MND
Non-invasive ventilation of a patient with MND

Section 1: Epidemiology and aetiology
Most GPs encounter only one or two patients with motor neurone disease (MND). As public awareness of MND increases, more patients may visit their GP seeking information.

Familiarity with common presentations and clinical features of MND will allow you to identify who should be referred to a neurologist.

When a patient is diagnosed, the GP becomes a key member of the multidisciplinary team. Therefore, it is important to anticipate the difficulties the patient may encounter as their disease progresses and to provide advice about symptomatic treatment and end-of-life care.

MND is the third commonest neurodegenerative disease after Alzheimer's disease and Parkinson's disease, with a prevalence of four to six in 100,000. The only proven risk factors for MND are increasing age and a genetic predisposition.

Although onset as early as 20 years of age is seen, most patients first develop symptoms in late middle age. The vast majority of MND occurs sporadically but approximately 10 per cent is inherited, mostly as an autosomal dominant trait.

Classification
In the UK, MND is an umbrella term used to refer to three related disorders of the motor neurone.

  • Primary lateral sclerosis (PLS) is a rare disorder affecting the upper motor neurone (UMN).
  • Amyotrophic lateral sclerosis (ALS) is the commonest form of MND, affecting UMN and lower motor neurones (LMN).
  • Progressive muscular atrophy (PMA) is predominantly a LMN form.

Most PLS patients develop some LMN signs and most PMA patients develop some UMN features. For this reason, most MND specialists consider PLS, ALS and PMA as part of a continuous spectrum.

The three main forms of MND. Upper motor neurones in red, lower motor neurones in blue

Section 2: Making the diagnosis
Clinical features

Presentation

MND most commonly begins with insidious and painless limb weakness. This may manifest as the dragging of a foot or difficulty doing up buttons.

Bulbar onset is common in older women, speech deterioration generally prefacing difficulty swallowing. Respiratory onset is rare but it is vital to consider neuromuscular respiratory insufficiency in cases of unexplained progressive dyspnoea. Regardless of presentation, MND is relentlessly progressive.

Wasting of the first dorsal interosseous muscle (arrowed)

Limb symptoms and signs
LMN loss causes muscle weakness and wasting. Intrinsic hand muscles and ankle dorsiflexion and hip flexion are often affected early. There may be fasciculation and cramp in any muscle.

UMN involvement causes increased tone experienced by the patient as limb stiffness. There may be ankle clonus.

Reflexes are brisk and plantars are upgoing. Eventually, patients are unable to support their own weight. Upper limb weakness may progress to the point when patients are no longer able to wash, dress or feed themselves.

Bulbar symptoms and signs
Bulbar involvement causes progressive dysarthria and dysphagia. LMN loss causes wasting, weakness and fasciculation of the tongue. Speech is nasal and palatal weakness may allow liquid to escape up into the nose on drinking.

UMN involvement produces a small, poorly mobile tongue and effortful, strained speech.

Pseudobulbar palsy describes UMN bulbar problems and the emotional lability that frequently accompanies them. Patients may eventually become entirely unable to speak (anarthria).

Dysphagia initially manifests as occasional coughing when eating or drinking. This is initially only a problem with some foods. Patients will take longer to eat and will lose weight.

Patients struggle to swallow medication and aspiration pneumonia is a risk. Swallowing saliva may be a problem, causing drooling, which is embarrassing and aspiration of saliva can cause pneumonia even in patients not taking food by mouth.

Respiratory involvement
Neuromuscular respiratory weakness develops insidiously, progresses and is often accompanied by a weak cough. Initially patients may be short of breath only on exertion, later they struggle at rest often preferring to sleep propped up in bed.

As respiratory muscle weakness progresses, patients begin to retain CO2 overnight. They feel unrefreshed on waking, are slow coming round and may suffer early morning headache.

Patients retaining CO2 often lose their appetite.

Cognitive involvement
The majority of MND patients remain cognitively intact. Psychological testing will reveal subtle deficits but many patients remain lucid.

A minority develop frontotemporal dementia. This may make MND more tolerable for the patient but is particularly difficult for relatives.

Diagnosis and investigation
The diagnosis of MND is made clinically. Imaging and neurophysiology exclude differentials and neurophysiology at presentation may identify subclinical LMN involvement.

There is no definitive diagnostic test. The diagnosis of ALS requires evidence of UMN and LMN degeneration in the absence of evidence of another cause.1 Pain and sensory symptoms are not features of MND and may suggest alternative diagnoses.

Early on ALS has a broad differential, which includes the mimics of PLS and PMA (see box). This differential narrows as the disease progresses and mixed UMN and LMN features develop throughout.

If a patient develops atypical features, the diagnosis must be reconsidered.

Differential diagnosis of the three forms of MND
ALS
  • Multi-level spinal cord and root compression.
  • Thyrotoxicosis.
  • Inclusion body myositis.
  • Dual UMN and UMN pathologies, for example cervical myelopathy and peripheral neuropathy.
PMA
  • Kennedy's disease (spinal bulbar muscular atrophy).
  • Chronic idiopathic demyelinating polyneuropathy.
  • Benign cramp fasciculation syndrome.
  • Multifocal motor neuropathy with conduction block.
PLS
  • Hereditary spastic paraplegia.
  • MS.
  • Spinal cord compression.

Section 3: Managing the condition
Care is best provided by a multidisciplinary team.2 Teams generally include a GP, neurologist, specialist nurse, physiotherapist, occupational therapist, speech and language therapist (SLT), dietitian and respiratory technician. A respiratory physician and gastroenterologist may also be involved.

Disease-modifying therapy
Riluzole reduces pre-synaptic glutamate release and has other likely neuroprotective effects. It is the only disease-modifying drug licensed for use in MND and may only be prescribed by a specialist to patients with the ALS form of MND under NICE guidelines.3

RCTs have shown that it prolongs life by only three to four months.

Symptomatic therapy
Given the aggressive nature of MND and the absence of effective disease-modifying therapy, patient care must be focused on relieving symptoms and the preservation of independence and quality of life for as long as is possible.

The management of respiratory and bulbar weakness is discussed below, while the table (right) summarises the management of other problems.

Nutritional management
MND patients require active nutritional management if excessive weight loss and dehydration are to be avoided. Weight loss reduces survival time and there is evidence enteral feeding lengthens survival time.4

Patients may have difficulty chewing and swallowing and upper limb weakness may make food preparation difficult.

Obtaining early advice from an SLT regarding safe eating techniques, such as sitting upright and the chin-tuck technique along with the modification of food texture often suffices.

A dietitian can help patients increase the calorie-content of the food they do eat.

A gastrostomy tube does not preclude patients enjoying food by mouth while they are still able

Gastrostomy tube placement
When conservative measures fail, gastrostomy tube placement should be considered. A gastrostomy tube allows medication, fluids and full nutritional support to be supplied. Many patients take their feed overnight. A gastrostomy tube does not preclude patients eating by mouth.

Some patients feel that when they are no longer able to eat their quality of life is so poor that they do not wish to prolong their lives by tube-feeding.

Respiratory management
There is good evidence that non-invasive ventilation (NIV) increases survival by up to seven months in selected MND patients with respiratory failure.5

NICE has recently published guidelines supporting the use of NIV in patients with MND.

Machines are small and a variety of face masks make it easier to find one that the patient can tolerate.

Ordinarily the machine is used only overnight at first.

Patients typically awake refreshed, without a headache and with more energy.

As the disease progresses patients will need the machine in the day and at end-stage NIV may be used continuously.

Patients with weak respiratory muscles can have difficulty coughing up secretions leading to mucous plugging of the small airways and pneumonia. A cough assist machine can be helpful in this situation.

Summary of the management of other MND symptoms
Problem  
Drooling Amitriptyline (syrup form) and/or hyoscine
hydrobromide patches applied behind the ear. If
these measures fail injection of botulinum toxin
into the salivary glands approximately every three
months.
Thick saliva Carbocisteine (syrup form) loosens difficult to
cough up saliva while coughing may be augmented by
a cough assist machine.
Difficulty getting food to mouth Modified cutlery helps weak hands grip and mobile
food to mouth arm supports position weak arms optimally.
Cramp Tonic water often suffices otherwise quinine
sulphate, 300mg at night.
Emotional lability An explanation that this is part and parcel of the
disease often suffices. Socially disabling
emotional lability can be treated with
amitriptyline or citalopram.

Section 4: Prognosis
MND is incurable. Death typically occurs two to five years after onset in ALS and PMA, most commonly due to aspiration pneumonia.

Some ALS patients die only a few months after diagnosis while PLS patients survive longer, often more than 10 years. Discussion of prognosis should be left to the neurologist.

It is important to be honest but at the same time offer some hope - most MND specialists have a few ALS patients who survive beyond 10 years.

In general, bulbar and respiratory-onset patients have shorter survival times than limb-onset patients, although percutaneous endoscopic gastrostomy feeding and NIV mitigate this to some extent.

End-of-life care
Given the communication difficulties common in advanced disease, end-of-life issues should be discussed in advance.

Unexpected deterioration secondary to aspiration pneumonia may otherwise result in unwanted intubation in A&E. Dementia raises complex ethical issues in end-of-life planning. Gastrostomy feeding and NIV would not normally be offered to patients lacking competence due to dementia. Patients may also be anxious about the terminal phase of the disease. Reassuringly, most patients die peacefully during sleep.

Sublingual lorazepam is helpful for laryngospasm and opiates should relieve longer periods of dyspnoea.

Most hospices now offer day centre respite for MND patients as well as terminal care.

Section 5: Case study
In 2006, Mrs P, a 71-year-old keen dancer, went to her GP complaining that her legs tired after walking no distance at all.

Her husband had noticed she was tending to trip when dancing. She started to have falls and was admitted to hospital for investigation. She had become difficult to understand and also started to cough when eating.

The doctor noted a positive jaw jerk, marked distal leg weakness, brisk reflexes and upgoing plantars. Mrs P was referred to a specialist who confirmed a diagnosis of limb-onset ALS in March 2007. Mrs P was referred to the MND multidisciplinary team and riluzole was started.

By June, she was unable to walk at all. Her bedroom was moved downstairs and a ramp laid to allow wheelchair access. By October, she was coughing more often on swallowing and her speech had deteriorated.

In January 2008, she was losing weight and reported dyspnoea when lying flat. In March, she complained of morning headache, which prompted admission to hospital for insertion of a gastrostomy tube and respiratory assessment.

Night-time NIV was started and tolerated. By July, Mrs P was suffering joint pain secondary to immobility. Her GP prescribed morphine.

In January 2009, Mrs P was admitted to a hospice and died two and a half years after first visiting her GP.

Section 6: Evidence base
Clinical trials

This Cochrane review of riluzole treatment of ALS concludes that riluzole 50mg twice daily does provide a modest survival benefit in ALS.

  • Bourke SC, Tomlinson, M, Wiliams 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: 140-7.

This trial of NIV in ALS gives good evidence that NIV confers a modest survival benefit and improves quality of life.

This Cochrane review of the evidence supporting enteral feeding in ALS concluded that there may be a survival benefit.

Guidelines

  • NICE. Guidelines on the use of non-invasive ventilation in the management of MND. CG105. London, NICE, 2010.

Key texts

  • Talbot K, Turner MR, Marsden R et al. Motor Neuron Disease. A Practical Manual. Oxford University Press, Oxford. 2009.

This book is a good and concise guide to the care of MND patients.

  • Lindquist UC. Rowing without oars. John Murray, London, 2005.

This is a moving patient account of living with MND.

Curriculum

The RCGP covers this topic in statement 15.7 Neurological problems.

Online

  • The website of the MND Association provides information about MND for healthcare professionals and patients. www.mnda.org
  • The ALS Association, which is based in the US, is another very well respected resource. www.alsa.org

Click here to reflect on this article and add notes to your CPD Organiser on MIMS Learning

CPD IMPACT: Earn more credits

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

  • Make a list of the neurological signs of MND, such as clonus, fasciculation and muscle wasting, as a revision aid.
  • Read about the ethics and law regarding end-of-life decisions and discuss it at your next practice meeting.
  • Make a template on your computer system to help others ask the right questions when considering the diagnosis and management of MND.

References
1. Brooks BR, Miller RG, Swash M et al. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disorders 2000; 1(Suppl 1): S57-60.

2. Traynor BJ, Alexander M, Corr B et al. Effect of a multidisciplinary amyotrophic lateral sclerosis (ALS) clinic on ALS survival: a population based study, 1996-2000. J Neurol Neurosurg Psychiatry 2003; 74: 1258-61.

3. NICE. Guidance on the use of riluzole (Rilutek) for the treatment of motor neurone disease. TA20. NICE, London, 2001.

4. Langmore SE, Kasarskis EJ, Manca ML et al. Enteral tube feeding for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev 2006 CD004030.

5. 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: 140-7.

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