Examine this patient's cranial nerves.

Examine this patient's upper limbs.

Examine this patient's lower limbs.



· Fasciculations and cramps: these may precede other symptoms by months.

· Painless, asymmetrical weakness of muscles of the upper limb or lower limb.

· Dysarthria and dysphagia.

· Emotional lability if there is bulbar involvement.


· Fasciculations, absent reflexes and weakness in the upper limbs.

· Spasticity, exaggerated reflexes and upgoing plantars in lower limbs.

· Sluggish palatal movements, absent gag reflex, brisk jaw jerk.

A combination of the above signs may be seen.


This patient has a combination of upper and lower motor neuron signs (lesions) due to motor neuron disease (aetiology), although I

would like to exclude cervical cord compression. The patient is wheelchair bound as a result of the disease (functional status).


What important cause should be ruled out before making a firm diagnosis of motor neuron disease?

Cord compression may produce a similar clinical picture and hence it is important to do an MRI scan of the spine and/or a

myelogram to exclude it.


What are the characteristic features of this disease?

· It rarely begins belore the age of 40 years.

· Presence of upper and lower motor neuron involvement of a single spinal segment, and motor dysfunction involving at least two

limbs or one limb and bulbar muscles.

· Sensory symptoms or signs are not seen.

· Ocular movements are not affected.

· There are never cerebellar or extrapyramidal signs.

· Sphincters are involved late, if at all.

· Remission is unknown and the disease is fatal within 5-7 years (due to bronchopneumonia).

What are the clinical patterns of motor neuron disease?

· Bulbar: bulbar or pseudobulbar palsy (25% of cases).

· Amyotrophic lateral sclerosis (50% of cases): flaccid arms and spastic legs.

· Progressive muscular atrophy (25% of cases): a lesion in the anterior horn cells affecting distal muscles. Characteristically

there is retention of deep tendon reflexes in the presence of severe muscular atrophy.

· Primary lateral sclerosis (rare): signs progress from an upper motor neuron to a lower motor neuron type.

Others affect lower motor neurons and include:

· Werdnig-Hoffman disease: presents in the neonatal period as a 'floppy infant' and is known as infantile progressive spinal

muscular atrophy.

· X-linked spinal muscular atrophy: the patient has associated testicular atrophy resulting in oligospermia and gynaecomastia. It

is associated with the ampli-fication of a trinucleotide repeat in the coding sequence of the androgen receptor gene; the severity

of the disease is directly related to the number of repeats present.

· Spinal muscular atrophy linked to locus on the large arm of chromosome 5.

What are the other types of motor neuron disease?

· Madras motor neuron disease is common in southern India. The onset is early (before the age of 30); asymmetrical limb

weakness and wasting, bulbar and facial involvement occur along with sensorineural deafness. The course is more

benign than the disorder observed in Europe and America (Srinivas K. Jagannathan K, Valmikinathan K 1984 The spectrum of

motor neuron disease in Madras. In: Rose FC, ed. Research Progress in Motor Neuron Disease, p. 142. London: Pitman).

· Amyotrophic lateral sclerosis associated with a parkinsonism-dementia complex in Guam (Science 1987; 237: 517). It also

tends to have an earlier onset and a more protracted course than the sporadic cases seen in Europe and America.

What is the pathology of motor neuron disease?

The clinical manifestations are a result of degeneration of Betz cells, pyramidal tracts, cranial nerve nuclei and anterior horn cells.

Both upper and lower motor neurons may be involved, but sensory involvement is not seen.

What is the explanation of fasciculation?

It results from spontaneous firing of large motor units formed by branching fibres of surviving axons that are striving to innervate

muscle fibres that have lost their nerve supply.

What are the cerebrospinal fluid (CSF) changes in the disease?

The CSF is usually normal (the protein level may be slightly raised).

What do you know about the heredity of amyotrophic lateral sclerosis ?

Most cases are sporadic. Five to ten per cent of cases are familial, and familial amyotrophic lateral sclerosis is linked to a gene on

the long arm of chromosome 21 (NEnglJMed 1991; 324: 1381). This genetic locus appears to be the copper-zinc-binding superoxide

dismutase gene, with various missense mutations identified in different families.

Is there any treatment for motor neuron disease?

No treatment has been shown to influence the course of the disease. Riluzole, a glutamate antagonist, is being used in limb or

bulbar palsy (N Engl J Meal 1994: 330: 585-91). Patients often require treatment for painful muscle cramps, constant drooling,

severe fatigability, sleep problems, incipient contractures, subluxation of the shoulder joint, dysphagia and neuralgia - all of which

can be ameliorated. Patients often have extreme lability of emotion, particularly in the early stages of amyotrophic lateral sclerosis.

In order to alleviate distress before or during respiratory failure, which is usually the terminal event, narcotic drugs should not be


What is the rationale for using riluzole?

The suggestion that accumulation of toxic levels of glutamate at synapses may cause neuronal death through a calcium-dependent

pathway. Riluzole has been shown to be useful in patients with disease of bulbar onset but not in those with disease of spinal onset.

The risk of death or tracheostomy is lower with 100 mg riluzole than placebo in limb or bulbar onset disease (Lancet 1996;

347:1425-31 ), but it is debatable whether this translates into an improved quality of life.

Is there any test to monitor the rate of disease progression?

Antibodies to L-type voltage-gated calcium channels are present in the serum of patients with sporadic amyotrophic lateral sclerosis,

and antibody titres correlate with the rate of disease progression (N Engl J Med 1992; 327:1721 8).

What is the role of magnetic cortical stimulation in amyotrophic

la teral sclerosis ? Magnetic cortical stimulation uses time-varying magnetic fields to induce electrical currents within the brain

painlessly. It is said to activate cortical motor neurons trans-synaptically through thalamocortical and corticocortical afferents, and

allows detection of degeneration of cortical Betz cells. In patients with amyotrophic lateral sclerosis the sensitivity of this technique to

detect upper motor neuron involvement in those with clinical signs is high, but the sensitivity of the technique in those without clinical

signs is unknown.

Is there any animal model for amyotrophic lateral sclerosis?

A transgenic mouse model possesses mutations in the gene encoding the cytosolic form of the enzyme copper-zinc superoxide

dismutase (Nature 1993; 362: 59).

kou Gehrig, the American baseball player, died from amyotrophic lateral sclerosis

50 years ago.

Charcot gave a detailed clinical and pathological description of amyotrophic lateral sclerosis in 1865.

Professor Stephen Hawking, the Cambridge theoretical physicist, is the most famous sufferer of motor neuron disease. It claimed

the lives of the actor David Niven, the football manager Don Revie and the wartime pilot Sir Leonard Cheshire, VC.