Basal Ganglia Disorders

Question 1

Striatum:

Answer 1

composed of:

• putamen
• caudate
• nucleus accumbens

Question 2

Subthalamic nucleus (STN):

Answer 2

• only excitatory nucleus in the striatum
• releases glutamate onto its targets

Question 3

2 main inputs to the striatum:

Answer 3

• Corticostriatal pathway
• Nigrostriatal pathway

Question 4

Corticostriatal pathway:

Answer 4

excitatory path from cortex to striatum

• mediated by glutamate
• cortical input to direct pathway ⇒ ‘accelerator’ & facilitates volitional movement
• cortical input to indirect pathway ⇒ ‘brake’ & inhibits volitional movement

Question 5

Nigrostriatal pathway:

Answer 5

dopaminergic pathways from substantia nigra to striatum

• results in opposing effects
• direct ⇒ excitation of striatum
  
  • ​striatum acts directly on the thalamus
• indirect pathways ⇒ inhibition of striatum
  
  • ​striatum acts indirectly on the thalamus via the STN

Question 6

Normal Striatal Effects:

Direct Pathway

Answer 6

Activation of direct pathway ⇒ GABA/substance P released ⇒ inhibits GPi & SNr ⇒ GABA not released onto VA/VL thalamus with release of inhibition ⇒ VA/VL thalamus is activated ⇒ releases glutamate ⇒ motor cortex is activated ⇒ facilitates movement

Question 7

Normal Striatal Effects:

Indirect Pathway

Answer 7

Activation of indirect pathway ⇒ GABA/enkephalin released ⇒ inhibits Gpe & SNr ⇒ GABA not released onto STN ⇒ STN is activated ⇒ releases glutamate onto Gpi/SNr ⇒ Gpi/SNr are activated ⇒ releases GABA onto thalamus ⇒ VA/VL thalamus is inhibited ⇒ motor cortex is not activated ⇒ inhibits movement

Question 8

Normal movement:

Answer 8

• Net corticostriatal & nigrostriatal effects on direct pathway results in activation of this pathway
• Net corticostriatal & nigrostriatal effects on indirect pathway results in inhibition of this pathway

Question 9

How is Parkinson’s disease defined?

Answer 9

• Loss of dopaminergic neurons in the SNc
• hypokinetic movement disorder
  
  • ​slower, smaller movements than normal

Question 10

What is the effect of Parkinson’s disease on the direct pathway?

Answer 10

SNc does not release dopamine (DA) onto striatum (the cholinergic interneurons) ⇒ striatum is inhibited ⇒ it does not release GABA/substance P onto Gpi/SNr ⇒ Gpi/SNr activated ⇒ activated & releases GABA onto thalamus ⇒ VA/VL thalamus is inhibited ⇒ inhibits movement

Question 11

What is the effect of Parkinson’s disease on the indirect pathway?

Answer 11

SNc does not release DA onto striatal cholinergic interneurons ⇒ activates striatum ⇒ GABA/Enk is released onto GPe ⇒ GPe is inhibited ⇒ Gpe does not inhibit STN ⇒ STN activated ⇒ releases glutamate onto GPi/SNr ⇒ GPi/SNr activated ⇒ Gpi/SNr releases GABA onto thalamus ⇒ VA/VL thalamus is inhibited ⇒ inhibits movement

Question 12

In Parkinson’s, the thalamus is _________, GPe is _________, & GPi is _________.

This results in __________ of movement.

Answer 12

• **Thalamus ⇒ **inhibited
• GPe ⇒ inhibited
• GPi ⇒ activated
• Result ⇒ inhibition of movement

Question 13

Parkinson’s Disease:

Clinical features (4)

Answer 13

1. Resting tremor (pill rolling)
   
   • ​​tremor of the hand/fingers that occurs at rest & looks as if a pill is rolled
   • usually in one hand, corresponding to dysfunction of contralateral striatum
2. Bradykinesia
   
   • slowness of movement
3. Rigidity
   
   • ​​increased resistance to passive movement of limb
4. Postural instability
   
   • tendency to fall (usually backwards)

Question 14

What are other clinical features of Parkinson’s disease?

Answer 14

Other clinical features:

• Sustained & good response to levodopa
• Asymmetric onset (one side of body affected first)
• reduced arm swing, stooped posture when walking
• en-bloc turning (turn require multiple small steps)
• difficulty rising from a chair
• hypophonia (low volume voice)
• hypomimia (ie. masked facies; reduced facial expressions)
• stooped posture, shuffling steps
• micrographia (handwriting is small)

Question 15

Parkinson’s Disease:

Treatment

Answer 15

• Levodopa (dopamine precursor)
  
  • taken up by dopaminergic neurons
  • released onto striatum
• Anticholinergics (benztropine/trihexyphenidyl)
  
  • inhibit effects of cholinergic interneurons in striatum & via the indirect pathway
  • GPe to be active ⇒ activates VA/VL thalamus ⇒ activates cortex ⇒ facilitates movement
• Deep brain stimulation of subthalamic nucleus or GPi
  
  • high frequency stimulation of STN or GPi results in inhibition of these nuclei ⇒ facilitates movement

Question 16

How is Huntington’s disease defined?

Answer 16

• Neurodegenerative disorder with loss of neurons primarily in the caudate
• Autosomal dominant
  
  • CAG repeat expansion
• Hyperkinetic movement disorder

Question 17

What is chorea?

Answer 17

• Chorea = “dance-like”, near continuous movement of limbs, face, tongue
  
  • found in Huntington’s disease
  • results in slurred speech

Question 18

What does a lesion of the caudate (Huntington’s disease) affect?

Answer 18

Caudate lesioned ⇒ no inhibition of GPe ⇒ GPe is activated ⇒ releases GABA onto STN ⇒ inhibits STN ⇒ glutamate is not released onto GPi/SNr ⇒ GPi/SNr is inhibited ⇒ VA/VL thalamus activated ⇒ motor cortex is stimulated ⇒ hyperkinetic movements

Question 19

Hemiballism:

Answer 19

• Hemiballism = brief, high amplitude, irregular movements of a limb
  
  • less dance-like than chorea
• Lesion of STN ⇒ hemiballism of the contralateral limb
• Usually caused by a stroke