Neurology - Motor neurone disease

Question 1

What is MND?

Answer 1

MND is an adult onset neurodegenerative disorder characterised by progressive degeneration of:

• anterior horn cells in the spinal cord
• cells of the lower motor cranial nerves
• neurones of the motor cortex with secondary degeneration of the pyramidal tracts

This produces spastic weakness, upgoing planters, hyporeflexia (UMN signs) as well as flaccid paralysis, wasting, fasciculations and hyporeflexia (LMN signs). There is little or no sensory, cerebellar, dementia or extrapyramidal involvement.

Question 2

What are the features of MND?

Answer 2

MND causes progressive weakness of limb, bulbar and respiratory muscles. Death typically ensues 3-5 years following diagnosis, most commonly due to respiratory failure.

Question 3

What age group is typically affected by MND?

Answer 3

It usually presents between the ages of 50 and 70. It is more common in men than women (1.5:1).

Question 4

What causes MND?

Answer 4

90% of MND cases occur sporadically.
Most familial cases are autosomal dominant. About 20% of these cases exhibit mutations in the antioxidant enzyme copper zinc superoxide dismutase (SOD1) gene.

Question 5

What mechanisms contribute to motor neurone degeneration in MND?

Answer 5

There are 2 theories:

i) excitotoxicity - over stimulation of glutamate receptors causing neuronal calcium overload
ii) free radical damage

Question 6

How is MND classified?

Answer 6

• amyotrophic lateral sclerosis (ALS): most common variant causing loss of upper and lower motor neurones (UMN and LMN signs) producing a mixed picture
• progressive muscular atrophy (PMA): predominantly LMN
• primary lateral sclerosis (PLS): predominantly UMN

Progressive bulbar palsy is considered a variant of ALS affecting the bulbar region

Question 7

What is the clinical presentation of MND?

Answer 7

• LMN weakness with wasting and fasciculation of the small muscles of the hand followed by wasting of upper and lower limb muscles
• LMN weakness, fasciculation and wasting of the tongue and pharynx producing dysarthria, dysphagia, choking and nasal regurgitation
• UMN spastic weakness starting in the legs and spreading to involve the arms

Question 8

How is MND diagnosed?

Answer 8

The diagnosis of ALS is clinical. includes:

• evidence (clinical, electrophysiological etc) of LMN degeneration
• evidence of UMN degeneration
• progressive spread of symptoms or signs within a region or to other regions
• no radiological, electrophysiological or pathological evidence of other disease

Question 9

What are the differential diagnosis to consider in the different subtypes of MND?

Answer 9

• ALS: multiple level spinal cord/ root compression, paraneoplastic syndromes, thyrotoxicosis, inclusion body myositis
• PLS: MS, spinal cord compression, hereditary spastic paraparesis
• PMA: multifocal motor neuropathy, Kennedy’s disease, spinal muscular atrophy, porphyria, lead poisoning

Question 10

What disease modifying therapy can be used in MND?

Answer 10

Riluzole is a drug that reduces presynaptic glutamate release has been shown in a small number of trials to extend the lifespan of patients with ALS by an average of 3-4 months. Its role in PMA, PLS remains unclear.

Question 11

What are some important aspects of MND care?

Answer 11

1) Nutritional support - most MND patients eventually develop progressive bulbar problems so advice regarding posture, airway protection and thickened fluids is important
2) Respiratory support - lung function tests should be performed at baseline, reduced FVC in the supine versus upright position is an early indicator of failure, NIPPV gives a survival benefit provided bulbar dysfunction is not severe