Background

The incidence of the disease is one to two per 100 000, and a general practice with 10 000 patients is likely to encounter a case of motor neurone disease every two to three years. The disease predominantly affects middle aged and elderly people, with a mean age of onset of 55 years, although younger people are occasionally affected. The disease is sporadic in 90% of cases, but about 10% are familial, usually with an autosomal dominant mode of inheritance.

The disease causes progressive injury and cell death of lower motor neurone groups in the spinal cord and brain stem and usually also of upper motor neurones in the motor cortex. Those affected typically develop a combination of upper and lower motor neurone signs, with progressive muscle weakness and wasting usually accompanied by pathologically brisk reflexes, eventually involving the limb and bulbar muscles. Clinical variants of the disease may affect purely the lower motor neurones (progressive muscular atrophy) or the upper motor neurones (primary lateral sclerosis). Death usually results from respiratory failure due to weakness of the ventilatory muscles.

The precise causes of the neurodegenerative process remain unknown. The selectivity of the disease process for the motor system is now recognised to be relative rather than absolute. …