Motor neurone disease

BMJ 2014; 349 –
A 59 year old man initially presented with weakness in his right leg and occasional trips. He had a longstanding history of mild low back pain and had a magnetic resonance image performed under the orthopaedic team that showed some cervical spondylolisthesis sparing the spinal cord. Four months after this, he went back to the general practitioner with progressive difficulty buttoning his shirt.

What is motor neurone disease?
Motor neurone disease is a devastating, incurable neurodegenerative disease of the motor neurones that primarily affects people in their 60s or 70s Of the four subtypes of motor neurone disease, the most common is amyotrophic lateral sclerosis. The subtypes vary clinically because they predominately affect different areas and have varying rates of progression.

How common is it?
• The incidence of amyotrophic lateral sclerosis is estimated to be 2.6 per 100?000 person years across Europe2
• A GP working full time for 30 years might expect to see one or two cases in his or her career.
• Diagnostic delays of 12-19 months from presentation have been reported. Two retrospective studies involving 130 patients showed that 27-61% of patients eventually diagnosed with motor neurone disease had been misdiagnosed, contributing to about 9-13 months of this delay.

Why is motor neurone disease missed?
Although motor neurone disease is a relatively well known rare disease, most GPs will diagnose only one or two cases in their career. There is a lack of awareness of the symptoms at presentation, when symptoms are often subtle.

The disease affects different anatomical regions, and it is estimated that about half of all patients with motor neurone disease are initially referred to non-neurology secondary care clinics. These are typically ear, nose, and throat clinics, because of bulbar symptoms such as dysarthria, and orthopaedics because of limb symptoms such as foot drop, which are often attributed to damage from spinal disease.
A lack of continuity of care can compound the delay in diagnosis further, because it is the progressive and multisystem nature of the symptoms that are the most indicative of the diagnosis.

The diagnosis is a difficult clinical one, and rates of misdiagnosis are high outside motor neurone disease specialist centres.
Therefore, it is recommended that if motor neurone disease is suspected, doctors refer urgently directly to someone with a special interest in the disease.

Why does this matter?
The median survival for patients with motor neurone disease has been reported as 30 months but varies with subtype. The diagnostic delay thus represents a substantial proportion of patients’ overall survival.
Treatments that modify the disease and support services are available for patients once a diagnosis is made, so it important to recognise the symptoms and signs early.

Good clinical care of symptoms through specialist multidisciplinary teams and motor neurone disease centres improves both quality of life and life expectancy.

How is motor neurone disease diagnosed?
Clinical features
Motor neurone disease causes a painless progressive weakness. It is helpful to think of symptoms in terms of systems affected.

Limb involvement is present at onset in about 70% of patients. This can be subtle, with a mild foot drop or a loss of manual dexterity leading to trips and difficulty with buttons or jar lids, respectively. On examination, there is a mixture of upper and motor neurone signs. Wasting and fasciculations can be seen.

At presentation, 20% of patients have bulbar features, with dysarthria usually preceding dysphagia. Patients might also mention excessive salivation or a choking sensation when lying flat. Patients’ voices can become weak and slurred, particularly when tired.

Respiratory involvement tends to be a late feature of motor neurone disease. Chest wall weakness causes hypoventilation and carbon dioxide retention, resulting in type II respiratory failure. This can present as lethargy, early morning headache, or dyspnoea.

Cognitive symptoms, especially changes in behaviour such as apathy and loss of social awareness, might be present at diagnosis and are increasingly recognised as important.

Investigations

Neurophysiological studies—for example, electromyography and nerve conduction studies—and magnetic resonance imaging are often used as an adjunct to diagnosis and to exclude differential diagnoses. The diagnosis is largely clinical, however, and is usually made by an experienced neurologist.

Delays in diagnosis from a patient’s perspective
“I just need to know now, I’m really struggling to work but until I get a diagnosis I can’t afford to just stop working. I know it sounds silly but now I’ve stopped crying and, as the prof said, we are one step away from knowing. I feel like I’m close to getting control back. Not that I want it to be MND [motor neurone disease ] because it’s almost like a death sentence, but not knowing is like a living hell that, for me, is worse.”

How is motor neurone disease managed?
Urgent referral of patients with symptoms and signs suggestive of motor neurone disease to a neurologist ,preferably one within the motor neurone disease care centre, is crucial so that a multidisciplinary team approach to their care can be initiated if necessary.

Riluzole, a glutamate release antagonist, and non-invasive ventilation are currently the only treatments for motor neurone disease approved by the National Institute for Health and Care Excellence.
A Cochrane review (four randomised controlled trials involving 1477 patients) concluded that riluzole probably prolongs survival by two or three months,another Cochrane review (one randomised clinical trial, 41 patients) suggests that non-invasive ventilation prolongs survival (perhaps by many months) and improves or maintains quality of life in those with better bulbar function.

GPs have an important role as care coordinators once the diagnosis is made. This includes identifying and treating symptoms, supervising treatment, facilitating frank discussions about end of life care and advanced decisions, and making referrals to palliative and other community services.

G Mohan.