Motor neurone disease
Progressive neurodegenerative disorder of upper and lower motor neurones.
1–2 per 100,000 per annum with a prevalence of 6 in 100,000.
Onset usually in middle age.
Men slightly more common than females.
Unknown cause, although in about 5% of cases, there is autosomal dominant inheritance and the condition has been localised to chromosome 21.
Motor neurone disease causes mixed upper and lower motor neurone signs. The ocular movements are not affected, there are never sensory, cerebellar or extrapyramidal signs, awareness is preserved and dementia is unusual. Three patterns are recognised depending on which group of motor neurones is lost first; however, most patients progress to a combination of the syndromes.
· Amyotrophic lateral sclerosis is disease of the lateral corticospinal tracts. Amyotrophy means atrophy of muscle. The clinical picture is that of a progressive spastic tetra or paraparesis with additional lower motor neurone signs. Typical clinical findings include spasticity, reduced power, muscle fasciculation and brisk reflexes with upgoing plantars.
· Progressive bulbar palsy is a disease of the lower cranial nerve nuclei and their supranuclear connections. The features are those of a bulbar and pseudobulbar palsy with upper and lower motor neurone signs, i.e. progressive loss of power in the muscles of facial expression, muscles of mastication, articulation and swallowing. The tongue appears wasted and fasiculating. There may be nasal regurgitation and an increased risk of aspiration pneumonia.
· Progressive muscular atrophy starts with muscle wasting in the small muscles of one hand and spreads throughout the arm. It often becomes bilateral over time. There is wasting and weakness with fasciculations and variable reflexes (increased if upper motor neurones affected at the level of the reflex, decreased or absent if lower motor neurones are affected).
There is loss of motor neurones from the cortex, brain stem and spinal cord. There is gliosis with secondary degeneration of the motor tracts. Inclusion bodies containing ubiquitin (a protein involved in the removal of damaged cell proteins) are found in the surviving neurones.
Weakness of respiratory muscles with risk of pneumonia and respiratory failure. Swallowing difficulties predispose to aspiration pneumonia.
There are no specific diagnostic tests. Denervation may be confirmed by electromyography, the CSF is usually normal although protein may be raised. MRI of the cervical spine is indicated if there are predominantly upper limb signs with or without lower limb upper motor neu-rone signs.
Supportive measures such as splints and crutches may be useful, and communication aids for dysarthria. Riluzole, a glutamate antagonist has been shown to improve prognosis by a few months.
Remission is unknown, the disease progresses gradually and causes death, often from bronchopneumonia. Survival for more than 3 years is unusual although there are rare ‘benign’ forms of the condition with prolonged survival.