Disorders of the motor neurone

Published on 10/04/2015 by admin

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Disorders of the motor neurone

The motor neurone, or anterior horn cell, lies in the anterior horn of the spinal cord. Its axon extends to the muscle and is the final common pathway for motor output. Disorders of the motor neurone are uncommon.

Motor neurone disease

The most common disease is motor neurone disease (MND), referred to as amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease in the USA. The annual incidence is 1 per 100 000 of the population. MND usually affects adults aged over 50 years, the risk increasing with increasing age, but occasionally younger adults may be affected. About 5% of cases may be familial, and in some of these, a genetic abnormality of the enzyme superoxide dismutase (SOD 1, a free radical scavenger) has been identified. The aetiology of the sporadic cases is unknown, but a toxic role has been postulated for the excitatory amino acid neurotransmitter glutamate. Other diseases of the motor neurone are now rare but poliomyelitis was common and its sequelae are still seen.

Pathology

There is degeneration of the motor cortex and anterior horns of the spinal cord with chromatolysis of the motor neurones, which may contain inclusion bodies, and degeneration of the corticospinal tracts and peripheral motor axons.

Clinical features

There are three main patterns of disease (Fig. 1). All are progressive and evolve at different rates. They overlap significantly and in the late stages tend to merge into a diffuse, combined upper motor neurone (UMN) and lower motor neurone (LMN) disorder. The differential diagnosis depends on the pattern of presentation. Sensation must be normal to make the diagnosis. The overall prognosis is poor; death is usually due to respiratory complications from bulbar or respiratory muscle weakness.

Fig. 1 Clinical features of motor neurone disease. (a) Amyotrophic lateral sclerosis; (b) progressive bulbar palsy; (c) progressive muscular atrophy.

Amyotrophic lateral sclerosis

This commonly presents with stiffness and weakness of the hands, muscle cramps and discomfort. In some cases, onset may be proximal, resembling a plexopathy or with foot drop, simulating peroneal nerve palsy. Over the following months, more widespread, patchy weakness appears that may affect any muscle, except the extraocular muscles. Weakness becomes more diffuse and spreads to the truncal and bulbar muscles. The hands appear severely wasted and there are often fasciculations in the interossei and sometimes other muscle groups. It may be necessary to observe the patient’s trunk and limb muscles for 30 s or more in order to see the fasciculations. Tone is usually normal and weakness is initially patchy. Despite wasting, reflexes are brisk and plantar responses usually become extensor during the disease. The most common differential diagnosis is cervical myeloradiculopathy, sometimes with additional lumbar radiculopathy.

Fifty per cent of patients die within 3 years and 90% by 6 years. A small number have a slower progression and survive over a decade.

Progressive bulbar palsy

This presents with progressive dysarthria until speech becomes unintelligible. Swallowing becomes difficult and patients spend hours trying to eat each day. They lose weight rapidly and may suffer repeated aspiration pneumonia. Emotional lability is common in this form and 10% of patients develop dementia later in the course of the illness. The tongue is usually wasted and fasciculating but moves stiffly, suggesting spasticity. The facial muscles sag and the jaw jerk and facial jerks are brisk. Although 25% of MND presents with this form, most patients later develop limb involvement. The differential diagnosis includes myasthenia gravis, brain stem lesions, cerebrovascular disease, multiple sclerosis and X-linked bulbospinal neuronopathy (see below). Most patients with this form of MND die within 3 years.

Progressive muscular atrophy

This is very uncommon. There is slowly progressive wasting, which is usually symmetrical in both hands. This progresses to more proximal muscles and to the legs over several years. Fasciculations may be present but there are no UMN signs. The differential diagnosis includes other LMN disorders: multifocal motor neuropathy with conduction block, inherited spinal muscular atrophy and post-polio syndrome (see below). Prognosis is best in patients aged under 50 years, with 72% surviving 5 years.

Investigations

There is no single test for MND. Investigations can exclude other causes and support the diagnosis but do not confirm it. Normal nerve conduction studies are used to exclude a neuropathy and electromyography to confirm denervation and show fasciculations in muscles not thought to be affected clinically. MRI may be needed to exclude other causes, depending on the site of clinical involvement: brain for bulbar symptoms and neck for LMN arm features. An MRI brain scan may show corticospinal degeneration.

Treatment

Treatment is supportive and involves most of the paramedical disciplines: physiotherapy (to optimize function, the best use of walking aids and to advise about positioning); occupational therapy (to optimize the patient’s environment); nursing; and speech therapy (to advise about swallowing and provide communication aids). Psychological support for the patient and relatives is important in a difficult, relentlessly progressive disease. Depression is common and can be treated.

Some drug therapy and other medical interventions are useful. Spasticity can be treated with baclofen. Patients with bulbar involvement may benefit from percutaneous insertion of a gastrostomy tube (percutaneous endoscopic gastrostomy; PEG), which is a simple procedure allowing direct enteral feeding to maintain nutrition and reduce the risk of aspiration pneumonia. PEG feeding also will allow patients who need hydration or parenteral medication to be looked after in most settings, at home or in a hospice rather than a hospital.

Some patients with respiratory weakness but otherwise good function may benefit from nocturnal or diurnal respiratory support. Typically respiratory support will help with symptoms of fatigue and headache, which may not be immediately recognized as symptoms of nocturnal hypoventilation. These are delicate, individual decisions as patients will continue to deteriorate and the respiratory support may prolong an unsatisfactory quality of life. Palliative care services can be very helpful in the managent of this relentlessly progressive condition.

Riluzole, a glutamate antagonist, has been shown to improve 18-month survival by 7%, a small but statistically significant benefit.

Polio and post-polio syndrome

Poliomyelitis is due to an RNA virus and usually occurs in childhood. Occasional cases occur in the UK after travel abroad or in susceptible adults who change the nappies of babies after they have received oral, live attenuated virus polio vaccine. The disease starts with a mild upper respiratory tract infection and may evolve into meningitis and encephalitis. In some of these cases, severe weakness may develop over 24 h affecting any pattern of muscles. Affected muscles become markedly atrophic and do not recover. Subsequent skeletal development is impaired and the typical post-polio limb is flaccid and small. Years later, the weakness of the limb may progress. The reason for this is unclear, but probably reflects anterior cell loss due to ageing from a severely depleted population of cells.

Inherited diseases of upper and lower motor neurones

Various rare conditions may include features of UMN and LMN disease. Those most likely to be confused with MND are as follows:

Spinal muscular atrophies. These present with pure LMN disorders. Inheritance is variable and there are three forms: rapidly fatal infantile (Werdnig–Hoffman syndrome), and slowly progressive juvenile (Kugelberg–Welander syndrome) or adult onsets. They are allelic variants of the same gene.

Hereditary spastic paraparesis (usually autosomal dominant). This presents with spasticity of the legs. The arms are stronger, often with compensatory hypertrophy.

Adrenoleucodystrophy (X-linked recessive). This presents with mixed UMN and LMN disease and mild adrenal insufficiency.

X-linked bulbospinal neuronopathy. This presents with bulbar palsy, pronounced action-induced fasciculations, diabetes, gynaecomastia, infertility and mild neuropathy. It is due to a defect of the androgen receptor and has a much better prognosis than MND.

Disorders of the motor neurone

Motor neurone disease is characterized by progressive upper and lower motor neurone signs with normal sensation.

There are three main patterns of disease with each different differential diagnosis.

There is no single diagnostic test for MND.

Treatment is mainly supportive.

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