Parkinson’s Disease

Background

• Parkinsonism is characterised by bradykinesia, rigidity, tremor and loss of postural reflexes.
• There are many causes but most common is Idiopathic Parkinson’s disease
  • e.g. drugs such as antipsychotics, metoclopramide, prochlorperazine, sodium valproate, lithium
  • e.g. other degenerative diseases (dementia with lewy bodies; progressive supranuclear palsy; multiple system atrophy; corticobasal degeneration; Alzheimer’s disease
  • e.g. other genetic diseases (Huntington’s; Fragile X tremor ataxia syndrome; spinocerebellar ataxias; Wilson’s disease)
  • Anoxic brain injury
• Incidence ~18/100,000 and prevalence of 180/100,000 of the general population (both increase with age: up to 500/100,000 in patients >80)
  • Average age of onset is 60 (fewer than 5% present <40- usually rare genetic forms)

Aetiology

• Majority idiopathic, with age a risk factor
• Rarely, genetic variants are seen (LRRK2- autosomal dominant- common in America/Middle East; Alpha-synuclein- autosomal dominant- rare; Parkin- recessive- young patients).
  • Having a 1st degree relative with PD increases risk 2-3 x
• Environmental factors could play a part as some chemicals have been shown to directly cause PD (e.g. pesticides/heavy metals; MPTP).

Pathophysiology

• Unknown initiating process but end result is loss of dominergic neurons in the substantia nigra of the basal ganglia with proteinous inclusions in the cells (classically α-synuclein aggregates, or Lewy bodies)

Presentation

• Non-motor symptoms may appear first (before classical motor symptoms)
  • e.g. hyposmia, constipation, restless leg syndrome/REM sleep disorder and insomnia
    • patients rarely present
  • Other common non-motor features include depression and anxiety; as well as autonomic disturbance e.g. orthostatic hypotension, erectile dysfunction, urinary dysfunction
• Motor symptoms are insidious.  Usually begin asymmetrically
  • Bradykinesia
    • Small handwriting (micrographia); difficulty tying shoes/doing up buttons
    • There is often fatiguing and decrease in size of repetitive movements
  • Tremor
    • Classic ‘pill-rolling’ tremor present at rest but absent with action/posture.  Most commonly affecting limbs (arms first), jaw and chin
    • Often exacerbated by walking (or other activities that take attention away from the tremor)
  • Rigidity
    • Cog-wheel rigidity is classical (due to rigidity + tremor); lead pipe rigidity can be seen in limbs unaffected by tremor
    • Stiffness and flexed/shrugged posture
• Other symptoms/signs can also be found
  • Expressionless face (hypomimia); soft voice (hypo-/dysphonia); impaired postural reflexes
  • Slow to start walking (failure of gait ignition); Rapid, short strides which tend to shorten with distance (festination); reduction of arm swing; impaired balance on turning
• Normal: Power; Deep tendon reflexes; plantar responses; Eye movements; Sensory and cerebellar examination
• Later on in disease progression, dementia is common (30-80%); hallucinations/psychosis can also develop

Investigations

• Largely a clinical diagnosis but dopaminergic imaging (SPECT/PET imaging) may help confirm the diagnosis (an absence of dopamine in the substantia nigra is seen)

Management

• Early PD with motor symptoms (I.e. patients in whom the diagnosis has been made and symptoms are causing functional impairment such to require treatment)
  • Levodopa + dopa decarboxylase inhibitor (Co-Careldopa (or Sinemet))

  • Side effect of LEVODOPA include: GI disturbance (take with food; discolouration of body fluids (red urine/tears); postural hypotension (can be severe and limit dose); EARLY neuro effects include dizziness, agitation, insomnia; LATE neuro effects include dyskinesia, psychosis and hallucination

  • Dopamine agonists (e.g. ropinirole, rotigotine (not in Tayside) or praminpexole- i.e. non-ergol derivatives only)
  • Mono-amine oxidase B inhibitor (e.g. selegiline)
• Late PD  (i.e. patients on levodopa who have developed motor complications)
  • MAO-B inhibitors
  • Dopamine agonists
    • Apomorphine
  • Catechol-o-methyl transferase inhibitors (e.g. Entacapone)
    • May reduce ‘off’ time in patients with fluctuating motor symptoms of PD
• Refractory and severe symptoms
  • Bilateral STN or GPi stimulation (Deep brain stimulation)
• In patients with psychotic symptoms
  • Use clozapine/atypical antipsychotics (not typical for risk of worsening motor symptoms)