Motor Neuron Disease (MND)


Relatively common disease, seen worldwide. There is degeneration of motor neurons in the motor cortex and spinal cord, affecting both upper and lower motor neurons.
  • MND never causes sensory problems
MND is a general term used to describe several types of motor neurone degeneration. Some clinicians (especially in the USA) do not use to the term MND, and instead refer to the individual types of degeneration, e.g.:
  • ALS – Amyotropic lateral sclerosis 75% of cases of MNDthis is the most common form of MND, and produces both UMN and LMN signs.
    • Both LMN and UMN signs can be present in the same muscle! – e.g. a wasted, fasciculating (LMN signs) muscle with hypereflexia (UMN sign)
    • Typically ALS consists of a progress weakness and wasting of the limbs
  • PBP – progressive bulbar palsy – 25% of cases of MND – presents as problems with speech and swallowing. Many patients may have bulbar and pseduobulbar signs.
  • PMA – Progressive Muscular Atrophy –typically only affects the LMN’s of the upper limbs
  • SMA – Spinal muscular Atrophy – characterised by wasting and weakness of muscles.
In many instances, MND and ALS are used interchangeably.
  • In many patients, as the disease progresses features of several of the different subtypes will be present in a single individual.


  • Incidence of 2 per 100 000
  • Slight male predominance
  • Usually middle aged onset (ALS)
    • PBP tends to present later, and may be slightly more prevalent in women
  • 5 year survival – from the time of first diagnosis is <10%.


Essentially unknown, but several factors may be involved:

Ageing – premature ageing of some motor cells can damage and destroy these cells. This puts extra pressure on the surviving cells to perform the original functions, and the increased metabolic processes, may damage the remaining cells.
Viral infection – not much evidence for this
Chemicals – some metals (lead, celenium, mercury and manganses) have been suggested, but nothing has yet been proven
Biochemisty – possible chronic calcium deficiency plays a role – there is an association with hyperparathyroidism.

  • this is also backed up by cases of gastric surgery. In such patients, MND incidence is increased, and there is reduced uptake of calcium.

Genetic – there is definitely a genetic component to some cases – and one specific gene mutation (chromosome 21) has been identified in some individuals. In such instances, there may be many cases within one family.

  • It is generally thought that the degeneration of nerves seen in MND is somehow genetically programmed.

Excitotoxicity – glutamate may play a role



The actual mechanisms of cell death are again similar to other neurodegenerative conditions. There will probably be:
  • Oxidative neuronal damage
  • Aggregation of abnormally large amounts of protein inside a cell
  • Glutamate problems (possible involving excitotoxicity)
  • Apoptosis
  • Prolonged caspase activity (contributing to the apoptosis)

Clinical features

Symmetrical weakness and wasting – usually at the extremities – 75% of patients

  • Wasting usually begins at the hand and spreads. It may initially be unilateral, but will soon become bilateral.
  • Fasciculation – this occurs as surviving axons branch out to new motor units and attempt to innervate them. Note that fasciculation is normally a LMN sign, but in MN, there are mixed upper and lower signs.
  • Cramps
  • There is usually NO PAIN

Bulbar and Pseudobulbar features –25% of patients -  dysphagia and dysarthria, nasal regurg (palate weakness) and choking. Swallowing solids may be difficult, tongue may be immobile. This is progressive. It mimicks both bulbar (LMN) and pseudobulbar (UMN) palsies. For example there may be:

  • Wasted, fasciculating tongue
    • Remember – fasciculations are motor units discharging spontaneously.
  • Weak palate
  • Eye movements are usually spared

Reflex problems – reflex may be lost, or they may become hyperreflexic:

  • Loss – is the result of motor neuron problems in the anterior horn
  • Hyperreflexia –due to loss of corticospinal neurons

there is no sensory loss, and sphincters are not affected.