Parkinson's disease

• Parkinson's is very common in over 65s but essential tremor is more common than Parkinson's disease (x8)
• what are the requirements to diagnose a patient with parkinsonism?


  • bradykinesia AND ONE OF THE THREE: (lead pipe) rigidity, resting tremor (4-6Hz), postural instability
• cogwheeling is the presence of rigidity plus lead pipe rigidity
• PD and genetics:

  • Parents of children with Gaucher’s disease are more likely to get PD (GBA homozygous)

  •Genetic PD is exception not the rule

  • PARK8 (AKA LRRK2) - ?

  • SNCA (PARK1/4) - Mutation in alpha-synuclein- first to be described but rare

  •PARK 2 (AKA parkin) –Problem with clearing toxic proteins
• what are the premotor symptoms associated with Parkinson's?

  • anosmia
  • REM-sleep behavioural changes
  • constipation
  • mood changes

  
• list some of the non-motor symptoms associated with Parkinson's

  • sexual dysfunction
  • weight loss or gain
  • depression
  • anxiety
  • sleep disturbance
  • hallucinations

  
• what are the main differential diagnoses when a patient comes in with symptoms that resemble parkinson's/parkinsonism?


  • essential tremor
  • vascular parkinsonism
  • Parkinson's plus syndromes
  • dementia with lewy bodies
• what is the difference between Parkinson's disease and dementia with Lewy bodies?


  • different progression of symptoms (pathway of preogression)
  • cognitive symptoms within a year of Parkinsonism or before
• what imaging could you do to differentiate essential tremor from Parkinson's disease? what would you see in both scans?


  DATscan

  see there is a common shaped appearance on the essential tremor but a fullstop/circle shape on the scan with Parkinson's

  this is because in parkinsons the level of dopamine in the synapses decreases so when it is imaged with a DATscan there is less highlighted overall

  NOTE - the dopamine is found in the synpases between the substancia nigra pars compactas projections and the striatum not the SNPC neurones themselves

  
• list pharmaceutical treatments for Parkinson's disease:


  • MOAB inhibitors
  • levodopa / co-careldopa / co-benldopa
  • COMT inhibitors
  • dopamine agonists
• outline the mechanism of action of MOAB inhibitors:


  Monoamine oxidase-B (MAO-B) is an enzyme in the body that breaks down several chemicals in the brain, including dopamine.

  MOAB inhibitors prevent the breakdown of dopamine in the body -> more dopamine available to the brain -> preventing the lack of stimulation -> This can modestly improve many PD movement symptoms.

  long acting drugs and can take a long time to flush out
• outline the mechanism of action for co-careldopa/co-beneldopa:

  contains levedopa and carbidopa/benserazide

  levedopa delivered to body and enters circulation -> aim for it to cross the blood brain barrier and be catalysed by dopa-decarboxylase into dopamine

  however dopa-decarboxylase is also found in the peripheral blood circulation which breaks down levedopa before it reaches the blood brain barrier and crosses

  use carbidopa/benserazide which inhibit the action of dopa-decarboxylase in peripheral circulation -> cannot cross the blood brain barrier and allow for dopamine in the brain

  
• describe the mechanism of action of ropinirole (dopamine agonist):


  • ropinirole
  • has affinity for D3 receptors in the brain -> acts on limbic system -> causes neuropsychiatric effects
  • can stimulate D2 receptors in the caudate-putamen system in the brain (essentially the striatum) -> this system affects movement -> improve the motor symptoms of Parkinon's
• outline the mechanism of action of Entacopone (COMT inhibitor):


  • COMT is an enzyme that breaks down (catecholamine) neurotransmitters like dopamine and adrenaline
  • Entacopone is an inhibitor so it prevents the breakdown of levodopa, it is especially effective with co-levodopa where there is also a dopa-decarboxylase inhibitor
  • higher levels of dopaminergic stimulation in the brain -> reduce the manifestations

  
• what are the MDT associated with the care of a person with parkinson's?


  • occupational therapist
  • PD specialist
  • PD nurse specialist
  • dietician
  • Speech and Language therapist
  • palliative care
  • psychiatry
• what are advanced therapies associated with PD?


  • deep brain stimulation
  • apomorphine - strong dopamine agonist (high affinity for D2, 3 and 5 receptors)
  • Carbidopa/levodopa intestinal gel
  • Foscarbidopa/foslevodopa subcutaneous
• dementia with lewy bodies is the same pathology as Parkinson's but it does not follow the BRAAK hypothesis with it beginning in the gut and progressing to the brain, different pattern of memory loss
• Apart from a DATscan what can differentiate an essential tremor from Parkinson's disease?

  ET lacks bradykinesia
• how does vascular parkinsonism present differently to Parkinson's / how to differentiate them?


  vascular parkinsonism

  • lower limb predominantly affected, gait issues
  • respond less well to levedopa
  • stepwise-reduction in function, wake and suddenly not okay then after every time period they are worse again
• how to differentiare Parkinson's from Parkinson's plus syndromes?


  • caused by tau proteins and alpha synuclein
  • neurodegenerative, caused by damage to the brain, gets worse over time
  • associated with falls
  • lose ability to swallow quickly
  • see eye abnormalities (supranuclear gaze palsy), they cannot voluntarily look down, but if fixed on a point can move their heads and achieve full range of movement through reflexes
• what are key features of MSA (multiple system atrophy) Parkinsonism


  • caused by alpha synuclein misfolding into a different shape
  • causes a change in REM sleep behaviour and autonomic dysfunction like a drop in blood pressure when standing, erectile dysfunction, bladder problems, sleep apnoea, sudden death

  2 types of MSA -> MSAP and MSA cerebellar which has cerebellar signs
• what is Foslevodopa/Foscarbidopa and how does it work?


  Foslevodopa/foscarbidopa, formerly known as ABBV-951, is a formulation of levodopa/carbidopa prodrugs with solubility that allows for subcutaneous (SC) infusion and is in development for the treatment of motor complications for patients with advanced Parkinson's disease.

  maintain a constant exposure to levedopa and carbidopa
• how does levedopa-carbidopa intestinal gel work?


  Levodopa-carbidopa intestinal gel is an approved treatment for advanced PD that continuously delivers levodopa through infusion into the proximal jejunum via a percutaneous endoscopic gastrostomy tube with a jejunal extension connected to a portable infusion pump.