Basal Ganglia and Parkinson's Disease

Question 1

Striatum =

Answer 1

Dorsal striatum and ventral striatum

Question 2

Dorsal striatum =

Answer 2

caudate and lentiform

Question 3

Neostriatum =

Answer 3

caudate nucleus and putamen

Question 4

Ventral striatum =

Answer 4

nucleus accumbens and olfactory tubercle

Question 5

Lentiform/Lenticular =

Answer 5

putamen and globus pallidus

Question 6

What are the basal ganglia? And name the main components

Answer 6

• Neostriatum (caudate nucleus and putamen)
• Paleostriatum (globus pallidus)
• Subthalamic nucleus
• Substantia nigra

Question 7

What are the main functions of the basal ganglia?

Answer 7

• Smooth movement
• Switching behaviour
• Reward systems
• Closely linked to thalamus, cortex and limbic system

Question 8

What sort of patterns do the basal ganglia generate?

Answer 8

• Basal ganglia thought to generate basic patterns of movement (motor programs)

Question 9

Where do all parts of the cerebral cortex project to?

Answer 9

• All parts of cerebral cortex project to corpus striatum, basal ganglia project to thalamus, thalamus projects to cerebral cortex (the motor loop)

Question 10

What does cortical activation of the putamen lead to?

Answer 10

• Cortical activation of putamen leads to excitation of supplementary motor area (SMAO by ventrolateral nuclei (VLN) of thalamus

Question 11

Draw a diagram of the direct pathway of the basal ganglia system

Answer 11

• Cortical excitation of neostriatum leads to distribution of thalamic nuclei
• Movement follows activation of putamen by cortical areas

Question 12

Draw a diagram of the indirect pathway of the basal ganglia components

Answer 12

• Cortical excitation of neostriatum leads to inhibition of inhibitory input to subthalamus

Question 13

What leads to activation of the direct pathway and inhibition of the indirect pathway

Answer 13

Activation of the dopamine pathway

Question 14

What is the MAIN function of the basal ganglia?

Answer 14

remove the inhibition on the thalamus

**The thamalus allows information to travel to the cortex and trigger movement with inhibitory signal removed

Question 15

What are the major clinical problems associated with the basal ganglia? And where does the defect occur

Answer 15

• Parkinson’s disease (substantia nigra deficit)
• Huntington’s disease (caudate deficit)
• Hemiballismus (subthalamic deficit)
• Wilson’s disease (lenticular)

Question 16

What are the clinical features of Parkinson’s Disease?

Answer 16

• Hypokinetic - decreased bodily movement
• Tremor at rest
• Rigidity – cogwheel, limbs > axial
• Bradykinesia
• Asymmetry
• Loss righting reflex
• 30% cognitive decline
• Hypomimia (lack of facial expression)
• Glabellar tap
• Quiet speech
• Micrographia

Question 17

What is the pathogenesis of Parkinson’s Disease?

Answer 17

• Bradykinesia, akinesia, rigidity
• Degeneration of dopaminergic neurons on substantia nigra

Question 18

Describe the features of Huntington’s disease

Answer 18

• Hyperkinetic - increased bodily movements
• Autosomal dominant
• CAG triple repeat disease (>40 repeats)
• Mutant huntingtin accumulates, toxic
• Chorea, behavioural disorders, dementia
• Caudate nucleus wasting

Question 19

What is the pathophysiology of the basal ganglia in Huntington’s Disease?

Answer 19

• Degeneration of caudate, putamen and globus pallidus

Question 20

What are the clinical features of Huntington’s disease?

Answer 20

• Hyperkinesia, dyskinesia
• Characterised by inappropriate or repetitive execution of movement patterns

Question 21

What type of genetic disorder is Wilson’s disease?

Answer 21

• Autosomal recessive

Question 22

What are the clinical features of Wilson’s Disease?

Answer 22

• Abnormal copper accumulation
• Hepato-lenticular degeneration (liver and brain)
• Dystonia, ataxia, subcortical dementia
• Copper transport, protein abnormality
• Low serum copper and caeruloplasmin
• Kayser-Fleisher rings

Question 23

What is the main treatment of Wilson’s Disease?

Answer 23

• Treatment = Penicillamine

Question 24

What is the main stratgey in the treatment of Parkinson’s Disease?

Answer 24

counteract the deficiency in dopamine in the basal ganglia

Question 25

What are the 5 main drugs used in the treatment of Parkinson's?

Answer 25

* Levodopa (in combination with carbidopa or benserazide) * Dopamine agonists (e.g. pramipexole, ropinirole and bromocriptine) * Monoamine oxidases B (MAO-B) inhibitors (e.g. selegiline and rasagiline) * Amantadine – releases dopamine * Muscarinic Acetylcholine Antagonist (trihexyphenidyl (benzhexol))

Question 26

What are the main sites of action of drugs used in Parkinson's?

Answer 26

Question 27

What is the first line treatment for Parkinson's?

Answer 27

* First line treatment for PD combined with a dopa decarboxylase inhibitor (cabidopa or benserazide) * This combination lowers the dose needed and reduces peripheral system side effects (e.g. nausea, hypotension)

Question 28

Why is there a limited time effectiveness of levodopa?

Answer 28

* Limited effectiveness with time as the neurodegeneration progresses

Question 29

What are the long term side effects of levadopa

Answer 29

* Involuntary writhing movements (dyskinesia) which may appear within 2 years. After face and limbs mainly. Occurs at peak therapeutic effect * Rapid fluctuations in clinical state. Hypokinesia and rigidity may suddenly worsen and then improve again. This on-off effect not seen in untreated PD patients or with other PD drugs. Reflects fluctuating receptor dynamics

Question 30

What are the main dopamin agonists that work on the D1 and D2 receptors? And what are their side effects?

Answer 30

Bromocriptine, cabergoline and pergolide (ergots) are orally active drugs that work on D1 and D2 receptors. They have limiting side effects – fibrotic reactions.

Question 31

Name the D2/3 selective dopamine receptor agaonists

Answer 31

Pramipexole and roprinole

Question 32

What are the amin MAO inibitiors and why are they used in combination?

Answer 32

* Selegiline & Rasagiline are a selective MAO-B which lacks the unwanted peripheral effects of non-selective MAO inhibitors. * Inhibition of MAO-B protects dopamine from extra neuronal degradation. * Combination with levodopa is more effective in relieving symptoms and prolonging life.

Question 33

What is amantadine and how does it work?

Answer 33

* Antiviral drug discovered to be beneficial in PD. * Increased dopamine release is primarily responsible for its therapeutic effect. * Less effective than levodopa or bromocriptine and action declines with time.

Question 34

What are the main acetylcholine anatgonists?

Answer 34

* Muscarinic acetylcholine receptors exert an inhibitory effect on dopaminergic nerves suppression of which compensates for a lack of dopamine. * Benzhexol, Orphenadrine and procyclidine can all be used, with usual anti- cholinergic side effects.