Parkinsons

Question 1

What is the underlying pathophysiology of PD

Answer 1

Neurodegeneration of the extra pyramidal system and loss of striata like dopamine

Question 2

What neurotransmitters cause what in PD

Answer 2

Loss of dopamine in the striatum causes motor problems
Loss of neuropeptides in the striatum also causes motor problems
Loss of NA and Ach in the Cortex- dementia
Loss of dopamine in Mesolimbic areas- psychiatric problems
Loss of hypothalamic amines -endocrine changes

Question 3

What can people with Parkinson’s do in terms of a motor plan

Answer 3

Can assemble motor plan (select from memory or assemble new sequence) but they are unable to specify accuracy of the programme and run/sequence them

Question 4

How can Parkinson’s be imaged

Answer 4

PET or SPECT Scan

Visualises and quantifies dopaminergic neuroma using radioactive ligands which bind to dopamine transporter proteins

Question 5

What is the cause of neuronal cell death in PD

Answer 5

Lewy bodies- eosinophilic inclusions with a core of alpha-synuclein aggregates form fibrils (dementia) in substantia nigra and locus coruleus

Question 6

What causes cell death in PD

Answer 6

Oxidative stress
Mitochondrial dysfunction
Proteosome dysfunction

Question 7

What drug treatments in terms of action are available for PD

Answer 7

Dopamine replacement 
Dopamine agonists
Dopamine metabolism blockers
Increase dopamine release 
Indirect dopamine enhancement

Question 8

What is the first line treatment for PD

Answer 8

L-DOPA + carbidopa

Question 9

What are alone side effects of L-DOPA

Answer 9

Choreic movements
Rapid fluctuations in clinical state
Nausea and anorexia
Hypotension 
Psychiatric effects

Question 10

Name a dopamine agonist and how it works

Answer 10

Ropinirole 
Full D2 (3>2>4) agonist, inhibits the inhibitory pathway of movement

Question 11

What is Selegiline

Answer 11

Monoamine oxidase inhibitor

May also protect against neurodegeneration

Question 12

How can DA release be enhanced

Answer 12

Amantidine, increases release and blocks reuptake

Question 13

How can DA release be indirectly enhanced

Answer 13

Adenosine A2a receptor antagonist

Question 14

Briefly describe the direct pathway of movement

Answer 14

Pro movement
Activation of striatal excitatory Medium spiny neurons expressing substance P from cortex
Increase strationigral GABA transmission
Decrease nigrothalamic GABA transmission
Increase thalamocortical glutamate transmission

Question 15

Briefly describe the indirect pathway of movement

Answer 15

Anti-movement
activation of medium spiny neurons expressing ENK from cortex
Increases straitopallidial GABA transmission
Decreases tonic inhibition on the subthalamic nucleus
Increased glutamate transmission to globus pallidus interna/ substantia nigra pars reticularis
Increased palliothalamic/nigrothalamic GABA tranmission
Decreased thalamocortical glutamate transmission

Question 16

What are the genetic causes of PD

Answer 16

Park1 gene codes for alpha-synulcein, autosomal dominant, early onset PD with Lewy bodies and marked rigidity
Park2 gene codes for Parkin- part of ubiquitin proteasomes- autosomal recessive early onset with no Lewy bodies and good Levodopa response
LRRK2 gene- sporadic PD

Question 17

What are some non-genetic causes of PD

Answer 17

Drug induced neurodegeneration

Viral encephalitis

Question 18

What at the symptoms of Parkinson’s disease

Answer 18

Early- resting tremor
Rigid posture/postural abnormalities
Mask like facial expression 
Akinesia
Poor slow movements 
Late- depression dementia and endocrine dysfunction