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• Parkinson's disease

  Progressive depletion of dopamine-secreting cells in the substantia nigra leading to motor symptoms, and in non-striatal pathways leading to neuropsychiatric symptoms
• Pathophysiology of Parkinson's disease


  1. Depletion of dopamine-secreting cells in the substantia nigra

  2. Depletion of dopamine-secreting cells in non-striatal pathways

  3. Accumulation of a-synuclein bound to ubiquitin forming Lewy bodies
• Causes of Parkinson's disease


  • Older age
  • Male gender
  • MPTP
  • Genetic factors (early onset, familial): Parkin gene, a-synuclein, ubiquitin carboxyl-terminal hydrolase L1
• The cause of Parkinson's disease is unknown
• Contributing factors to Parkinson's disease include older age, male gender, MPTP, and genetic factors
• Genetic factors leading to early onset, familial Parkinson's disease


  • Parkin gene
  • a-synuclein
  • ubiquitin carboxyl-terminal hydrolase L1
• Parkinson's disease


  • Onset after age 50
  • Men and women equally affected
• Tremor


  1. 4-7 Hz

  2. Pill-rolling

  3. At rest

  4. Better with movement

  5. Worse with anxiety

  6. Usually affects upper limbs

  7. Unilateral then affects ipsilateral lower limb

  8. Becomes bilateral
• Rigidity


  • Lead pipe or cogwheel when combined with tremor
• Akinesia


  • Difficulty in initiating movement
• Bradykinesia


  • Slowing of voluntary movements
• Repetitive movement


  • Progressive fatiguing and decreased amplitude
• Symptoms


  • Mask face
  • Unblinking
  • Positive glabellar reflex
  • Slow monotonous speech
  • Dysarthria
  • Micrographia
  • Dysphagia
• Symptoms


  • Stooped posture
  • Shuffling gait with small steps
  • Poor arm swing
  • Freezing episodes
  • Tendency to fall (late disease)
• Symptoms


  • Early personality changes
  • Dementia in advanced disease
• Autonomic symptoms


  • Orthostatic hypotension
  • Drooling of saliva
  • Constipation
  • Excess sweating
• Anosmia (Loss of sense of smell)
• Psychiatric symptoms


  • Depression
  • Hallucinations
  • Dementia
  • Impulsive behaviors
• Commonest cause of death is bronchopneumonia
• Diagnosis is clinical, lab has no role
• Levodopa/Carbidopa


  Mainstay treatment
• Levodopa/Carbidopa


  • Early side effect: Hallucinations
  • Late side effect: Involuntary movements
  • On-off phenomenon due to dose-response relationship
• Dopamine agonists


  Ropinirole/Pramipexole/Bromocriptine/Rotigotine. Used in early disease
• Dopamine agonists


  • Side effects: Impulse control disorders, daytime sleepiness
• Monoamine oxidase B inhibitor


  Selegiline/Rasagiline. Used in early disease as an adjunctive agent
• Monoamine oxidase B inhibitor


  • Side effects: Confusion and insomnia
• COMT inhibitor


  Entacapone/Tolcapone. Not given alone
• Amantadine


  Used in early or mild disease
• Amantadine


  • Side effects: ankle edema and livedo reticularis
• Anticholinergics


  Benztropine/Trihexyphenidyl. Used when tremor is major finding and young patient; not used in older or demented patients
• Anticholinergics


  • Side effects: Dry mouth, blurred vision, constipation, nausea, urinary retention
• Apomorphine


  Used for intermittent rescue for off periods
• SSRI or tricyclic antidepressant amitriptyline

  For depression
• Deep brain stimulation


  For patients with insufficient medical therapy or who develop severe disease before age 40
• Dopaminergic drugs are reduced after DBS, but not withdrawal
• Secondary causes of hypokinetic movement disorders


  • Drug induced (e.g. Dopamine receptor blocking drugs)
  • Post encephalitic
  • Wilson's disease
  • Trauma: dementia pugilistica
• Dementia pugilistica


  • Boxers are prone to get this due to chronic trauma to the head