Epidemiology

• Incidence: Approximately 1–3 per 100 000 per year.
  
• Mean age at the onset: 60 years (male:female ratio = 1.7:1).
  
• Main risk factors: Increasing age, gender and family history.
  
• Twenty-five per cent of MND patients present with PBP.

Aetiology

• Sporadic:

Most cases; unknown aetiology.

Toxic role for the excitatory amino acid neurotransmitter glutamate suggested.

• Genetic:

Family history seen in 5–10%.

Some rare families show autosomal dominant transmission.

In almost 20% of familial cases, a mutation on chromosome 21 in the gene encoding the free radical scavenging enzyme copper/zinc superoxide dismutase (SOD1) is seen (exactly how this produces motor neurone degeneration is unknown, but potentially oxidative injury occurs as a result of increased free radical production).

Associations/Risk Factors

See section ‘Epidemiology’.

Pathology/Pathogenesis

• Degeneration of pyramidal cells within the motor cortex and corticospinal tracts produce UMN signs.
  
• Degeneration of large anterior horn cells in the spinal cord and brainstem motor nuclei produce LMN signs.

History

Onset typically occurs in the following:

• One arm leading to weakness of grip.
  
• One leg causing foot drop.
  
• Followed by generalisation of the symptoms with eventual involvement of truncal and bulbar muscles.

PBP

• Common in older women.
  
• Related to degeneration of lower motor nerves in the brainstem (bulb).
  
• Usually presents with dysarthria and dysphagia (wasted, fasciculating tongue and wasted pharyngeal muscles).
  
• Often combined with a pseudo-bulbar syndrome (UMN-type syndrome with emotional lability; stiff tongue; spastic dysarthria; brisk facial, snout and jaw jerk reflexes and nasality).
  
• Limb involvement usually follows within months.

Examination

• Demonstrates combined UMN (spastic tonal increase, pyramidal pattern weakness, pathologically brisk reflexes and upgoing plantars) and LMN (wasting, fasciculation, weakness and reflex loss) signs in various affected regions.
  
• Careful examination reveals the absence of visual, sensory or cerebellar signs.