• Only a few environmental causes have so far been identified.
  
• Never smokers are twice as likely to develop PD. Low caffeine intake slightly increases the risk of developing PD.
  
• Certain environmental toxins, such as exposure to the designer drug MPTP, and carbon monoxide poisoning can produce a parkinsonian disorder but this is not the same as idiopathic Parkinson’s disease.

Genetic:

• Mendelian-type genetic mutations account for approximately 5% of patients with Parkinson’s disease in the United Kingdom. The most common autosomal dominant mutations producing PD are in the gene LRRK-2.
  
• The most common autosomal recessive mutations causing parkinsonism are in the parkin gene.

Pathology

• Motor symptoms in PD are due to the degeneration of the dopaminergic projection extending from the cell bodies in the substantia nigra of the mid-brain to the terminal innervation of the striatum (putamen and caudate nucleus) in the basal forebrain.
  
• The Lewy Body, composed of misfolded synuclein, found in the perikarya of the dopamine neurones of the substantia nigra is the histopathological hallmark.
  
• Extensive pathology in other monoaminergic systems, outside the dopaminergic nigrostriatal pathway, and the change in cholinergic and glutamatergic pathways are also seen.

History

• The onset is typically in one or the other upper limbs, typically asymmetric (due to greater degeneration of the contralateral nigrostriatal pathway).
  
• Tremor, difficulty with fine finger movement, micrographia, difficulty turning in bed and reduced walking speed.
  
• Approximately 5% of patients present with what appears to be a frozen shoulder.
  
• Often at presentation, patients complain of slowing with activities of daily living, such as washing or dressing.

Examination

• Tremor is typically asymmetric, present at rest and improved by action, increased by mental strain and is of a 4–6 Hz frequency.
  
• Rigidity refers to an increase in limb tone i.e. equal throughout the range of movement (in contrast to spasticity, which demonstrates a catch on tone testing). Typically asymmetric.
  
• Bradykinesia refers to not only a reduction in amplitude and speed of movement but also to fatiguing over time, as seen on repeated finger tapping.
  
• Stooped posture.
  
• In the early stage of disease, a reduction in unilateral arm swing is seen on walking. Subsequently, gait is stooped and shuffling and may demonstrate festination and freezing.
  
• Postural instability may be revealed by unsteadiness or occasional stumbling on corner turning with the patient taking several steps backwards or needing to be caught on draw testing.

Investigations

Table 19.1 Differential diagnoses of Parkinson’s disease with differentiating features.