RLS Readings

Question 1

MRI imaging of RLS patients did not reveal a brain abnormality. Instead what was found in RLS patients? 4 How was this confirmed? 3

Answer 1

There was an iron deficiency in the putamen, caudate nucleus, substantia nigra and thalamus.
The deficiency was confirmed via low levels iron, ferritin and transferrin in the substantia nigra

Question 2

What do PLMS suggest about the pathophysiology of RLS?

Answer 2

They suggest that origin may be spinal hyperexcitability.

Question 3

What brain areas are implicated in RLS? 5

Answer 3

Brains involved in:
1) Movement
2) Sensation
3) Emotion
4) Arousal
5) Multimodality
Are implicated in RLS

Question 4

What has been found with regards to dopamine in RLS?

Answer 4

It was initially thought that RLS resulted from a dopamine deficiency.
However, studies have an over activity of the dopamine system in the brain. This over activity results in a down regulation of the D2 receptors in the putamen and an increase in tyrosine hydroxylase in the substantia nigra.
At night when circadian influences result in a relative dopamine deficit with low dopamine receptor levels, RLS symptoms may emerge.

Question 5

It has been suggested that there is a malfunction of central iron acquisition and transport in RLS patients. What evidence is there to support this? 3

Answer 5

1) Several studies have shown low ferritin levels and RLS
2) RLS improves with administration of oral and intravenous iron
3) CSF ferritin levels are 65% lower and transferrin levels are 3 times higher in RLS patients as compared with age matched controls.

Question 6

What evidence is there for the role of the opioid system?

Answer 6

It has been shown that endogenous opioids are significantly decreased in RLS patients.

The iron, dopamine and opioid systems interact and it has been shown that opioid receptor agonist protects dopaminergic cells from cell death

Question 7

Explain the glutamatergic system in RLS

Answer 7

1) Glutamate is an excitatory neurotransmitter
2) studies have shown that there is increased glutamatergic activity in the thalamus in RLS patients.
3) alpha 2 delta ligand treatment has been shown to improve RLS symptoms. This treatment results in a decreased glutamate release