Parkinson's

Question 1

What are the causes of Parkinson’s disease?

Answer 1

Dopaminergic neurons in the substantia nigra gradually die → malfunction of nigrostriatal pathway

Clumps of misfolded proteins form within neurons – most commonly Lewy bodies
- α-synuclein form small repeated units of oligomers or longer fibrils
- When there is too much misfolded α-synuclein, usual protein clearing systems (e.g. proteasomes, autophagosomes) are overwhelmed, leading to neuron death

Mitochondrial function is also slower in Parkinson’s, leading to neuronal death due to unmet energy needs
- Old mitochondria get broken down by autophagosomes, but autophagosome system is slower in Parkinson’s, leading to accumulation of damaged/worn-out mitochondria

Microglia also take up the resulting cellular debris from the neuronal death, triggering an immune response
- Release of cytokines – activate neighbouring microglia and astrocytes
- Chemicals released by activated microglia and astrocytes injure neurons

Question 2

How does the initial clinical presentation of Parkinson’s look like?

Answer 2

Asymmetric

Positive response to levodopa or apomorphine

Postural instability and falls absent (at this point in time)

Less rapid progression (at this point in time)

Autonomic dysfunction not present yet

Neuroimaging
- MRI: only for differential diagnosis of other parkinsonian syndromes
- Single photon emission computed tomography (SPECT), dopamine transporter imaging (DaT) – to differentiate essential tremors and other non-dopamine deficiency etiologies

Possibly impaired olfaction

Question 3

What are the diagnosis criteria?

Answer 3

2 of the 3 cardinal signs must be present:
- Tremor – resting tremor (disappears w movement), increases w stress
- Rigidity – “ratchet”-like stiffness (cogwheel rigidity), also leadpipe rigidity
- Akinesia/bradykinesia – subjective sense of weakness, loss of dexterity, loss of facial expression, reduced blinking, difficulty getting out of bed/chair, difficulty turning while walking