Parkinson’s disease – clinical

Question 1

Parkinsonism is a clinical syndrome consisting of…

Answer 1

• bradykinesia/hypokinesia (slowness and poverty of movement)
• (resting) tremor
• rigidity (stiffness)

Question 2

What characterizes parkinson’s disease?

Answer 2

The degeneration of substantia nigra dopaminergic neurons, which causes motor symptoms.

Question 3

What changes are seen in the substantia nigra in patients with parkinson’s disese?

Answer 3

Macroscopic indications:
- depigmentation
- paleness

Microscopic indications
- neuronal loss
- gliosis (i.e. changes in glial cells)
- intraneuronal Lewy bodies, that mainly consist of asynuclein.

Question 4

What are the risk factors of parkinson’s disease?

Answer 4

• Age is most important
• Genetic factors
• Gender (higher risk in men)
• Environment - many correlations, many are still unclear
• Gut microbiome (correlation)
• Antibiotic exposure (correlation)

Question 5

Is Parkinson’s disease heredetary? What genes are associated with the disease?

Answer 5

• PD is mostly a sporadic, multifactorial disease
• Around 10% have a positive family history
• Mutations in PARK genes

Question 6

What are the motor symptoms of parkinson’s disease?

Answer 6

• Hypokinesia: smallness of movement
• Akinesia: Can’t move, or movement stops
• Rigidity: Stiff muscles or resistance
• Tremor
• Postural instability: Forward bent posture, impaired balance

Question 7

What are the clinical diagnosis criteria of parkinson’s disease?

Answer 7

• Parkinsonism
• Bradykinesia and either rigidity or resting tremor (or both)
  ((Bradykinesia: slowness of movement))

Question 8

How is parkinson’s disease often diagnosed?

Answer 8

By exclusion of other possibilities

Question 9

What drug is central to parkinson’s treatment, and what does it do?

Answer 9

Levodopa - it is a dopamin replacement: it will enter the body, can penetrate the BBB, and metabolizes to dopamin in the brain.
Levodopa treats the symptoms, not the cause!

Question 10

What is the basic principle of treating parkinson’s?

Answer 10

To enhance striatal dopaminergic activity

Question 11

Why are parkinson’s patients not treated with dopamin?

Answer 11

Dopamin cannot cross the blood-brain barrier, instead Levodopa is used, which can cross this and metabolizes to dopamin in the neurons.

Question 12

What are the common drug targets when treating parkinson’s disease symptoms?

Answer 12

• Direct delivery of dopamin (or precursor)
• Inhibition of dopamin breakdown (MAO-B or COMT inhibitors)
• Dopamin receptor agonists

Question 13

What device aided treatment options exist for Parkinson’s disease?

Answer 13

• Levodopa infusions
• Apomorphine infusions
• Deep brain stimulations