Parkinson's disease

Definition | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management

Definition

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterised by bradykinesia (slowness of movement), rigidity, resting tremor, and postural instability due to dopamine deficiency in the basal ganglia.

Aetiology

The exact cause of Parkinson’s disease is unknown, but it is thought to result from a combination of genetic and environmental factors.

1. Genetic Factors:

  • Approximately 10–15% of cases have a genetic component.
  • Mutations in genes such as LRRK2, PARK7, PINK1, and SNCA have been linked to PD.

2. Environmental Factors:

  • Exposure to pesticides and herbicides.
  • Heavy metal exposure (e.g., manganese).
  • Head trauma.
  • Rural living and drinking well water (associated with pesticide exposure).

Pathophysiology

  • Degeneration of dopaminergic neurons in the substantia nigra (part of the basal ganglia).
  • Leads to reduced dopamine levels in the nigrostriatal pathway, causing motor symptoms.
  • Presence of Lewy bodies (abnormal protein aggregates containing α-synuclein).
  • Imbalance between excitatory (acetylcholine) and inhibitory (dopamine) neurotransmitters.

Risk factors

  • Age (risk increases over 60 years).
  • Family history of Parkinson’s disease.
  • Male sex (PD is more common in men).
  • Environmental toxin exposure (pesticides, heavy metals).
  • History of traumatic brain injury.

Signs and symptoms

The classic motor symptoms of PD develop gradually and often begin unilaterally before progressing bilaterally.

Cardinal Motor Symptoms ("TRAP"):

  • Tremor: resting tremor (pill rolling) that decreases with voluntary movement.
  • Rigidity: increased muscle tone, "cogwheel" rigidity on examination.
  • Akinesia/Bradykinesia: slowness of movement, difficulty initiating voluntary movements.
  • Postural Instability: impaired balance and frequent falls in later stages.

Non-Motor Symptoms:

  • Cognitive impairment: executive dysfunction, dementia in later stages.
  • Depression and anxiety.
  • Autonomic dysfunction: orthostatic hypotension, constipation, urinary urgency.
  • Sleep disturbances: REM sleep behaviour disorder, restless legs syndrome.
  • Hyposmia (reduced sense of smell).
  • Micrographia: small, cramped handwriting.

Investigations

  • Clinical diagnosis: based on characteristic motor symptoms.
  • DaTSCAN (dopamine transporter scan): Differentiates PD from other tremor disorders.
  • MRI brain: used to rule out structural causes (e.g., stroke, tumour).
  • Autonomic function tests: assess for autonomic dysfunction in atypical PD.

Management

1. Pharmacological Treatment:

First-Line Treatment:
  • Levodopa (combined with carbidopa or benserazide): most effective symptomatic treatment.
  • Used in moderate to severe disease.
Alternative First-Line (Mild Disease, Younger Patients):
  • Dopamine agonists (e.g., pramipexole, ropinirole): Can delay levodopa use.
  • MAO-B inhibitors (e.g., selegiline, rasagiline): reduce dopamine breakdown.
Adjunct Therapies:
  • COMT inhibitors (e.g., entacapone): prolong levodopa effect.
  • Amantadine: used for dyskinesias.
  • Anticholinergics (e.g., trihexyphenidyl): help with tremor but cause cognitive side effects.

2. Non-Pharmacological Management:

  • Physiotherapy for mobility and fall prevention.
  • Speech therapy for swallowing and speech difficulties.
  • Occupational therapy for daily activity adaptations.
  • Dietary support to prevent malnutrition and constipation.

3. Advanced Treatment Options:

  • Deep brain stimulation (DBS): for patients with severe motor fluctuations despite medication.
  • Apomorphine infusion: for severe motor fluctuations when oral therapy is inadequate.

4. Palliative Care:

  • End of life planning for late stage disease.
  • Carer support and symptom control.
NeurologymypanotesParkinson's disease