Clinical background

Sporadic motor neurone disease (MND) is progressive, unremitting, and affects about 1/100 000 of the population with a prevalence of between 2 and 7/100 000 and a 1.2 to 1.5/1 male to female ratio. Outside the United Kingdom it is known as amyotrophic lateral sclerosis (ALS) since its major characteristics are focal muscle wasting and degeneration of the lateral corticospinal tracts (i.e. both upper and lower motoneurone involvement). The relative degree of upper and lower motor neurone involvement varies between patients.

Focal wasting of limb muscles results from degeneration of specific groups of spinal motor neurones (seen alone this ‘lower motor neurone’ disorder is progressive muscular atrophy). Progressive bulbar palsy results from degeneration of lower cranial motor nuclei, and hyperreflexia is consequent upon death of cortical Betz cells (seen alone this ‘upper motor neurone’ disorder is primary lateral sclerosis). While sensory systems are considered generally unaffected in disease of shorter duration, sensory involvement may occur in some cases (Swash & Schwartz, 1992). MND therefore is primarily selective for motor neurones controlling striated muscle (i.e. ‘somatic’ motor neurones) and synaptically coupled to corticospinal systems.

However, in MND of shorter duration, preservation of eye movement, and bladder and anal sphincter function, coupled with post-mortem evidence of sparing of oculomotor neurones in the 3rd, 4th and 5th cranial nuclei, and sacral sphincteric motor neurones in Onuf's nucleus (Mannen et al., 1977; Tokoyura, 1977), suggests that not all motor neurones die.