Parkinson's Disease

• What are the premotor features of Parkinson's disease?

  Anosmia

  REM sleep behaviour disorder

  Constipation

  (Mood changes)
• Pathophys PD

  Damage to neurons throughout brain (esp. substantia nigra) -> due to misfolding of alpha-synuclein -> associated with Lewy bodies & neuronal cell death 

  Likely to interplay between genetic & environmental factors 

  A-synuclein, when misfolded -> tends to spread (more misfolding) 
• What are 2 autosomal dominant genetic mutations that increase the risk of PD?

  PARK8

  SNCA (PARK 1/4) -> mutation in alpha-synuclein
• What is an autosomal recessive mutation that increases the risk of PD?

  PARK 2 (aka parkin) -> problem with clearing toxic proteins
• Parkinson's is a clinical diagnosis, not test that can be done for diagnosis.

  Follow UK Brain Bank Criteria

  1. Diagnosis of Parkinsonism
  2. Exclusion critea for PD
  3. Supportive critea for PD

  DaTSCAN can support a diagnosis
• Give 5 non-motor symptoms of PD?

  Swallowing problems

  Hallucinations

  Orthostatic hypotension

  Urinary symptoms
• What are the main differential diagnosis of PD?

  Essential tremor

  Vascular Parkinsonism

  Parkinson's plus syndromes

  Dementia with Lewy bodies
• How can essential tremor be differentiated from PD?

  Have postural tremor

  No bradykinesia

  No increased tone

  Gait is usually unaffected
• How can Vascular Parkinsonism be differentiated from PD?

  VP

  Unilateral features after 3 years

  Repeated strokes with stepwise progression

  Will have lower limb predominance

  Respond less well to levodopa
• How can Parkinson's plus syndromes be differentiated from PD?

  Will have cerebellar signs

  Will have early severe disautonomy
• How can dementia with Lewy bodies be differentiated from PD?

  Will have early severe dementia with disturbances of memory, language or praxis

  Onset of cognitive symptoms < 1 year from Parkinsonism (or before)
• What is shown in the image?


  Normal DaTSCAN

  Comma appearance of substantia nigra

  
• What are the advanced therapies for PD?

  Deep brain stimulation -> can stimulate/inhibit structures around electrodes

  Apomorphine -> dopamine agonist

  Carbidopa/levodopa intestinal gel (Duodopa) -> levodopa straight into jejunum

  Foscarbidopa/foslevodopa (Produodopa)
• What is the MDT for PD?

  Parkinson's Disease Nurse Specialist

  Dietician

  Occupational therapist

  Speech & language therapist

  Specialist in PD

  Psychiatry

  Palliative care
• MOA - Levodopa


  Levodopa (L-dopa) is a dopamine precursor

  Levodopa crosses the BBB (via various routes) -> decarboxylated by dopa decarboxylase to form dopamine -> stimulates dopaminergic receptors
• MOA - Carbidopa


  Dopa decarboxylase inhibitor

  Carbidopa binds to & inhibits dopa decarboxylase in the periphery → less decarboxylase of L-dopa to dopamine in the periphery → more L-dopa crosses the BBB → increased dopamine in the brain 
• How can dopamine agonists be used in PD?


  Activates dopamine receptors in the body → mimics effect of dopamine 
• How can monoamine oxidase-B (MAO-B) inhibitors be used in PD?

  Inhibits MAOB → increases extracellular levels of dopamine in striatum → increased dopaminergic activity 
• How can catechol-O-methyltransferase (COMT) inhibitors be used in PD?

  Inhibits COMT in synaptic cleft → stops breakdown of dopamine into homovanillic acid (HVA) → more dopamine within the synaptic cleft 
• COMT inhibitors cannot be used as a monotherapy, have to be used with co-beneldopa or co-careldopa.
• What is shown in the image?

  DaTSCAN for PD