The term ‘degenerative’ underlines a present lack of understanding of the aetiology of this group of progressive diseases of the nervous system.
Motor neurone disease (MND) In this disease there is progressive degeneration of motor neurones in the spinal cord, in the somatic motor nuclei of the cranial nerves and within the cortex. The condition is sporadic and of entirely unknown cause. Though not familial, rece t work has assigned the gene for the condition to chromosome 21. The prevalence is about 6 in 100000, with a slight male predominance. The onset is in middle life. The sensory system is not involved.
There are three patterns:
1 Progressive muscular atrophy
2 Amyotrophic lateral sclerosis
3 Progressive bulbar palsy
Although useful as a means of understanding the disease, these are not distinct aetiological or pathological variants; the three merge later in the course of the condition. Progressive muscular atrophy
Wasting often begins in the small muscles of one hand and spreads inexorably throughout the arm. Although it may begin unilaterally, wasting soon follows on the opposite side.
Fasciculation is common. It is due to the spontaneous firing of abnormally large motor units formed by the branching fibres of surviving axons that are striving to innervate muscle fibres that have lost their nerve supply. Cramps may occur but pain does not. The physical signs are of wasting and weakness, with fasciculation that is often widespread. Tendon reflexes are lost when the reflex arc is interrupted (by anterior horn cell loss) but are often preserved or exaggerated because of the loss of motor neurones in the corticospinal tracts.
Amyotrophic lateral sclerosis (ALS)
‘Lateral sclerosis’ means disease of the lateral corticospinal tracts (i.e. a spastic paraparesis). ‘Amyotrophy’ means atrophy of muscle (which would be unusual in most other forms of spastic tetraparesis or paraparesis). The clinical picture is thus of a progressive spastic etraparesis or paraparesis with added LMN signs and fasciculation. ALS is the term usually given to MND in the USA. Progressive bulbar palsy Here the brunt of the onset of the disease falls upon the lower cranial nerve nuclei and their supranuclear connections.
Dysarthria, dysphagia, nasal regurgitation of fluids and choking are common symptoms. For reasons unknown, this form of the disease is more common in women than in men. The characteristic features are of a bulbar and pseudobulbar palsy, i.e. a mixture of UMN and LMN signs in the lower cranial nerves, e.g. a wasted fibrillating tongue with a spastic weak palate.
The ocular movements are not affected. There are never cerebellar or extrapyramidal signs. Awareness is preserved and dementia is unusual. Sphincter disturbance occurs late, if at all. Remission is unknown. The disease progresses, spreading gradually and causes death, often from bronchopneumonia. Survival for more than 3 years is most unusual, although there are rare ‘benign’ forms of the condition in which survival is prolonged.
There are no specific diagnostic tests and the diagnosis can often be made on clinical grounds alone. Cervical radiculopathy and myelopathy and the rare (almost extinct) syphilitic cervical pachymeningitis may sometimes cause diagnostic difficulty. Bulbar myastheniagravis may sometimes appear similar in the early stages. Denervation may be confirmed by electromyography, which characteristically shows chronic partial denervation with preserved motor conduction velocity. The CSF is usually normal (the protein may be slightly raised).No treatment has been shown to influence the course of this disease although recently Riluzole, a glutamate antagonist, has been shown to help, particularly in patients with disease of bulbar onset. Management of patientswith MND, who are often well-informed and aware of the outlook, is particularly difficult. Spinal muscular atrophies These are a group of rare genetically determined disorders of the motor neurone that give rise to slowly progressive, usually symmetrical, muscle wasting and weakness. An acute infantile type (Werdnig-Hoffman disease), a chronic childhood type (Kugelberg-Weilander disease) and adult forms are recognized. Clinically these conditions may be confused with muscular dystrophies, hereditary neuropathies or MND .
This is a diffuse deterioration in mental function producedby a number of pathological processes. The commonest is Alzheimer’s disease.