Parkinson's Disease

Question 1

What is the pathophysiology of Parkinson’s Disease?

Answer 1

• Loss of dopaminergic neurones within the substantia nigra
• Surviving neurones contain Lewy bodies
• Accumulation of alpha synuclein in Lewy bodies which then become toxic to the cells around it
• PD manifests after 50% of dopaminergic neurones are lost
• Suggested mechanisms for Lewy body formation include oxidative stress, mithchondrial failure, excitotoxicity, protein aggregation, interferance with DNA transcription, NO, inflammation, apoptosis, trophin deficiency and infection

Question 2

What are the stages of pathological progression of PD?

Answer 2

• Stages 1-2 = medulla, pons and olfactory nucleus (presymptomatic or premotor)
• Stages 3-4 = midbrain, substantia nigra pars compacta (Parkinsonism only becomes evident after extensive nigral damage)
• Stages 5-6 = neocortex involvement (development of PD dementia)

Question 3

What are the clinical features of PD? (4 cardinal features in bold)

Answer 3

• Motor
  
  • Bradykinesia - handwriting gets smaller and smaller, small steps/shuffling gait, difficulty initiating movement, difficulty turning, reduced facial movements/expression
  • Muscle regidity - resistance to passive movement, cogwheel
  • 4-6Hz resting tremor - improves on movement, worse when distracted
  • Postural instability
• Neuropsychiatric (dementia, depression, anxiety)
• Sleep (REM sleep behavious disorder, restless legs syndrome, daytime somnolence)
• Autonomic (constipation, urinary urgency/nocturia, erectile dysfunction, excessive salivation/sweating, postural hypotension)
• Other (reduced olfactory function, fatigue, pain and sensory problems)

Question 4

How is PD diagnosed?

Answer 4

• Clinical diagnosis (NICE recommends the UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria)
• Can use FP-CIT SPECT (functional imaging) to look for loss of dopaminergic neurones

Question 5

How is PD treated?

Answer 5

• Synthetic dopamine (Levodopa)
• Peripheral decarboxylase inhibitors - stop dopamine being broken down peripherally (Carbidopa, benserazide)
• Dopamine agonists - mimic domapine (ropinirole, pramipexole, rotigotine, apomorphine)
• MAO-B inhibitors - stops MAO-B enzyme breaking down dopamine (selegiline, rasagiline)
• COMT-inhibitors - slows breakdown of Levodopa (entacapone, tolcapone)
• Deep brain stimulation of subthalamic nucleus

NB - The main side effects of dopamine include dystonia, chorea and athetosis.

Question 6

Parkinson’s-plus syndromes

Answer 6

• PSP - think centre of body
  
  • Parkinsonism
  • Cognitive impairment
  • Vertical gaze palsy - can’t look up or down (move head with eyes fixed cephalic?)
  • Swallowing difficulty
  • Neck dystonia/rigidity
  • Falling backwards
• MSA - think autonomic symptoms
  
  • Parkinsonism
  • Postural hypotension
  • Bowel and bladder control issues
  • Excessive sweating
  • Erectile dysfunction
  • Speech or bulbar dysfunction
  • Pyramidal or cerebellar dysfunction
• Dementia with Lewy Bodies
  
  • Progressive cognitive decline
  • Visual hallucinations
  • Delusions
  • Disorders of REM sleep