Parkinson's

Question 0

Onset of Parkinson’s

Answer 0

Late 50s to 60s

Question 1

Percentage of the population with Parkinson’s

Answer 1

0.3%

Question 2

Three characteristics of Parkinson’s

Answer 2

Tremor
Rigidity
Bradykinesia

Question 3

Parkinson’s main Neurodegenerative characteristic

Answer 3

Degeneration of the pathway connecting the substantia nigra to the striatum in the midbrain.

Question 4

L-Dopa Carlsson et al (50s)

Answer 4

Levodopa can cross the blood-brain barrier
Converts to dopamine in the brain
In animals: L-dopa increases dopamine, decreases PD

Question 5

L-Dopa

Hauser (09)

Answer 5

L-dopa works inside existing dopamine neurons
As they’re lost, becomes less effective
40-75% develop dyskinesia after 4-6yrs of L-dopa
Drug response recedes with treatment
Many patients don’t respond at all

Question 6

Excitation and inhibition model of Parkinson’s

Answer 6

A. Neocortex sends info to the thalamus via direct/indirect routes, creating positive/negative feedback
B. feedback is modulated by dopamine, accounting for 2 movement disorders:

Hypokinesia - increased thalamic inhibition from the basal ganglia, cause by a loss of dopamine.
Hyperkinesia - reduced th inhibition through direct pathway

Loss of dopamine to the striatum = excessive basal ganglia output

Treatment - increase dopamine input in striatum/reduce basal ganglia output to thalamus

Question 7

Parkinson’s experimental models

6-OHDA

Answer 7

Causes dopamine cell death, restricted to substantia nigra if injected there.

High levels present in PD brains and pee.
Used in primates as a PD model - better models exist.

Question 8

Experimental models of PD

Discovery of a better model

Answer 8

MPTP - the frozen addicts
Langston et al (83) had taken MPTP and crossed the blood-brain barrier, converted into MPP+ by glial cells, selectively kills nigra-striatal dopamine neurons.

Similar pathology and symptoms to PD
Respond to L-dopa similarly

Question 9

Parkinson’s experimental models
The better model
Bergman, Whichmann & Delong (90)

Answer 9

MPTP monkeys, recorded in STN before applying subthalamomotomy. After MPTP, basal ganglia increased TN activity.
Lesion in STN - recovered within a minute from lesion.

Question 10

Parkinson’s

Patel et al (03)

Answer 10

21ss with PD
Gave radio frequency lesioning of the STN
Followed for 12m minimum
Improved in contra lateral tremor, rigidity, bradykinesia.
L-dopa daily intake was halved, reduction in dyskinesia, safe lesions.

But: permanent and highly invasive

Question 11

Deep brain stimulation

Answer 11

Reversible, less invasive and adjustable
Stimulates area around basal ganglia to alleviate symptoms. Electrodes are implanted into subcortical areas, connected to implanted stimulators that excite/inhibit neuronal activity.

Question 12

Deep brain stimulation

Kraak et al (03)

Answer 12

Off medication, improved 1,3&5yrs after surgery
Able to live independently for longer
Even better if combined with medication