Definition

Motor neurone disease (MND) is characterized by the progressive deterioration of the anterior horn cells of the spinal cord and the corticospinal tracts, causing lower motor neurone lesions and upper motor neurone lesions respectively. Certain motor nuclei of the brainstem may also be affected, leading to bulbar paralysis. Degeneration of the motor neurones leads to weakness and wasting of muscles, a loss of mobility in the limbs and difficulties with speech, swallowing and breathing.

Incidence

The incidence is about 2 per 100 000, with a familial form found in about 1% of all cases [1]. MND tends to be a disease of later middle life; the mean age of onset is 58 years, with a slightly higher percentage of males affected.

Mortality

The mean duration of survival after diagnosis is 3–4 years, although this can vary greatly according to the type of MND and the part of the nervous system most seriously affected.

Amyotrophic lateral sclerosis (ALS)

This is the most common form of MND, accounting for about 66% of all patients [2], with both upper and lower motor neurones affected. It is characterized by weakness and wasting in the limbs, often first indicated by clumsiness in walking or handling things. Most commonly the upper limbs and hands are affected first with evident wasting of the thenar eminence. Average life expectancy with this form can be between 2 and 5 years from onset of symptoms.

Progressive bulbar palsy (PBP)

PBP involves both upper and lower motor neurones and affects about a quarter of the patients diagnosed. This form of MND often causes difficulties with speech or swallowing. If the lower motor neurones are affected, the tongue tends to atrophy with visible fasciculation and reduced mobility. This results in a rather nasal type of speech. If the upper motor neurones are affected the tongue is spastic and tends to cause dysarthria, difficulty with the mechanics of speech, i.e. stuttering.

Wild mood swings may also occur with little apparent cause. The limbs are less affected but as the disease progresses the patient may experience weakness in the arms and legs [3]. Life expectancy is between 6 months and 3 years from the onset of symptoms.

Progressive muscular atrophy (PMA)

PMA affects only a small group of people, with damage mainly occurring in the lower motor neurones. It tends to start earlier, predominantly affecting men below the age of 50 years. It first presents with wasting in the arms, manifesting as weakness and clumsiness of the hands. There may be progression to the lower limbs but bulbar involvement is rare until late in the disease. The rate of progression is much slower, with patients living 5–10 years after diagnosis.

There are other much less common variants: Kennedy’s disease, Guam variant MND and primary lateral sclerosis.

Although ALS, PBP and PMA are the three main forms of MND there is an enormous variation in symptoms between patients. Control of bladder or bowels is rarely affected. Mental deterioration and dementia are found in less than 5% of patients [3]. There is increasing evidence of frontal lobe involvement which may lead to emotional lability. Anxiety and depression are quite commonly found, unsurprisingly, in such a serious disease.

Risk factors

There are no apparent risk factors although, as mentioned above, there can be, rarely, a familial link.

Differential diagnosis

MND presents some problems with diagnosis for several reasons: primarily because it is comparatively rare, but also because the early symptoms do not appear serious to the patient. These can include clumsiness, mild weakness or slightly slurred speech, all of which could have an innocent cause. It may be some time before a doctor is consulted.

The classification and terminology used to describe the different MND syndromes are not always clear or consistent, with ALS being frequently used in US information sources as the general title.

Tests

There is rarely a clear pattern or a single indicative symptom and no definitive test. MND does not usually affect the bladder or bowel. It can be confirmed by electromyography later in the progress of the disease when the motor action potentials are of increased amplitude and duration but fewer in number than normal. Other investigations may be necessary to exclude syringomyelia or cervical spondylosis, both of which may present with weakness in the upper limbs.

Pharmacology

The National Institute for Clinical Excellence has recommended the use of riluzole (Rilutek) to treat ALS. It is thought to prolong life for a couple of months and may delay the need for a tracheostomy, but it does not really help with many of the symptoms. The drug reduces the natural production of the neural transmitter glutamate, which carries signals to the motor neurones. It is believed that too much glutamate can damage these and inhibit nerve signalling.

Other medicine may help with symptoms. Muscle relaxants such as baclofen, tizanidine and the benzodiazepines may reduce spasticity. Glycopyrrolate and atropine may reduce the flow of saliva. Quinine or phenytoin may decrease cramps. Anticonvulsants and non-steroidal anti-inflammatory drugs may help relieve pain, and other drugs can be prescribed to treat depression. Tranquillizers often help with sleeping problems.

Some patients with PPS develop sleep apnoea (a potentially life-threatening condition characterized by interruptions of breathing during sleep), which can be treated with decongestant therapy or assisted breathing at night. Panic attacks over fears of choking to death can be treated with benzodiazepines. Botulinum toxin may be used to treat jaw spasms or drooling. Amitriptyline and other anticholinergic drugs can help control excess drooling. Some patients may eventually require stronger medicines such as morphine to cope with musculoskeletal abnormalities or pain, and opiates are used to provide comfort care in terminal stages of the disease.

Surgery

Surgery can occasionally be used to remove any blockage to the airway but is not generally applied to this disease.

Impact on the patient

The manifest problems can be subdivided into the following categories.