The Basal Ganglia and Parkinson's Disease

Question 1

Label this diagram of the basal ganglia

Answer 1

Question 2

What is the basal ganglia and name the parts

Answer 2

Deep cerebral nuclei; Neostriatum (caudate nucleus and putamen), paleostriatum (globus pallidus), Subthalamic nucleus and substantia nigra (pars reticulata and pars compacta)

Question 3

What is the functions of the basal ganglia?

Answer 3

• Smooth movement, switching behaviour, reward systems and closely linked to thalamus, cortex and limbic system.
• Thought to generate basic patterns of movement

Question 4

What is the direct pathway of the basal ganglia?

Answer 4

Cortical excitation of neostriatum leads to inhibition of globus pallidus internal via GABA which prevents its normal function of sending inhibitory signals to the thalamus. Therefore the thalamus can send excitatory signals to the cortex, allowing stimulation. Thought to allow movement

Question 5

What is the Indirect pathway of the basal ganglia?

Answer 5

Cortical excitation of neostriatum causes inhibiton of globus pallidus external, preventing it from preforming its normal function of inhibiting the subthalamic nucleus. Therefore allowing the subthalamic nucleus to send excitatory signals to the globus pallidus internal, allowing it to send inhibitory signals to the thalamus, preventing movement.

Question 6

What is the role of the Pars Compacta of the Substantia Nigra?

Answer 6

It releases dopamine which does to act on D1 and D2 receptors in the direct and indirect pathways. When it binds to D1 receptors it allows for activation of the direct pathway and when it binds to D2 receptors it causes inhibition of the indirect pathway. This tips the balance between the two pathways and allows for movement to occur.

Question 7

What are some potential clinical problems that arise due to deficits in the substantia nigra?

Answer 7

• Parkinson’s disease (pars compacta deficit) which causes hypokinetic, bradykinesia and hypertonia.
• Huntington’s disease (caudate deficit) which causes hyperkinetic and hypotonia.
• Hemiballism (subthalamic deficit) which causes hyperkinetic and violent, involuntary movements.
• Wilson’s Disease (lenticular) Which is associated with copper deposition and involuntary movements.

Question 8

What are the clinical features of Parkinson’s disease?

Answer 8

• Tremor at rest,
• Ridigity,
• Bradykinesia,
• Asymmetry,
• 30% have cognitive decline,
• Hypomimia (lack of facial expression),
• Glabellar tap,
• Quiet speech,
• Micrographia

Question 9

What is the pathophysiology underlying Parkinson’s disease?

Answer 9

Degeneration of dopaminergic neurons of substantia nigra pars compacta. Therefore you decrease the amount of dopamine present, which in turn decreases the direct pathway stimulation and increases inhibitory pathway stimulation. This will increase inhibition on the thalamus and cause slowing of movements

Question 10

What is the pathophysiology of Huntington’s Disease?

Answer 10

Autosomal dominant genetic condition which results in the degeneration of caudate, putamen and globus pallidus. This indirect pathway is preferentially affected which results in less inhibition of the thalamus so movements increase and are faster.

Question 11

What is Wilson’s disease?

Answer 11

AN autosomal recessive condition which leads to abnormal copper accumulation due to copper transport protein abnormality. Clinical sign is Kayser-Fleisher rings. Treatment is penicillamine which mops up excess copper

Question 12

What are chemical treatment options for Parkinson’s disease?

Answer 12

As there is decreased dopamine you want to increase the amount the patient has however you can’t give them just dopamine as it doesn’t cross the BBB so give levadopa as it does pass the BBB adn can then be converted into dopamine.
You can also give dopamine agonists, MAO inhibitors (more effective if combined with levadopa), Amantadine (increases dopamine release) can be beneficial and acetylcholine antagonists (used to be gold standard)

Question 13

What is the first line treatment of PD?

Answer 13

Levadopa combined with a dopa decarboxylase inhibitor such as Carbidopa or Benserazide) as this reduced peripheral system side effects such as nausea and hypotension.

Question 14

What are the long term side effects of levodopa?

Answer 14

• Dyskinesia which may appear within two years, mainly affects face and limbs.
• Hypokinesia and rigidity which may fluctuate due to the fluctuating levels of levadopa in the blood stream
• There is also no evidence it can slow neurodegeneration

Question 15

Name some Dopamine agonists and their features

Answer 15

• Bromocriptine and pergolide (ergots) are oral drugs that work on D1 and D2 receptors but have limiting side effects of fibrotic reactions.
• Pramipexole and ropinirole are D2/3 selective receptor agonists. Better tolerated but short half life (6-8hours).
• Rotigotine (newer transdermal patch)
• Apomorphine ( given by injection to control off-effect of levadopa)

Question 16

Name some MAO inhibitors and their features

Answer 16

Selegiline and rasagiline which are selective for MAO-B. They selectiveness prevents unwanted peripheral side effects of non-selective MAO inhibitors.
The inhibition protects dopamine from extraneuronal degradation. When combined with levadopa it can relieve symptoms and prolong life.

Question 17

Name some acetylcholine antagonists and their features

Answer 17

Benzhexol and procyclidine. Muscarinic acetylcholine receptors exert an inhibitory effect on dopaminergic nerves, suppression of which compensates for lack of dopamine

Question 18

What can be used in severe cases of Parkinson’s Disease?

Answer 18

Electrote stimulation of the Subthalamic of GPi nuclei by inserted electrodes. It can improve motor dysfunction.