Restless legs syndrome is characterised by an uncomfortable, often irresistible urge to move the legs, typically worse in the evening and night, provoked by rest, and partially or completely relieved by movement. It is among the most common causes of difficulty falling asleep and is frequently mistaken for anxiety, joint pain, or circulation problems.
Diagnostic Criteria
The International RLS Study Group (IRLSSG) 2014 criteria require all of the following: an urge to move the legs accompanied by uncomfortable sensations; the urge worsens during rest; the urge is partially or completely relieved by movement; the urge is worse in the evening or night; and these symptoms are not explained by another condition. Meeting all five criteria, with functional impairment, establishes the diagnosis without any investigations.
The Iron Deficiency Connection
Brain iron deficiency is central to the pathophysiology of RLS regardless of whether serum iron markers appear normal. Iron is essential for dopamine synthesis through its role as a cofactor for tyrosine hydroxylase. Post-mortem studies of RLS patients consistently show reduced iron in the substantia nigra. Critically, central iron deficiency can occur even when serum ferritin appears adequate: a serum ferritin below 75 micrograms per litre is associated with RLS symptoms and supplementation to above 100 mcg/L often produces significant symptom improvement. The standard laboratory reference range for ferritin (12 to 300 mcg/L) is therefore inadequate as a threshold for RLS management.
Iron Supplementation Protocol
- Oral iron: ferrous bisglycinate or ferrous sulphate 325mg with vitamin C; taken on an empty stomach every other day (evidence that alternate-day dosing is better absorbed than daily)
- Target ferritin above 100 mcg/L (some guidelines recommend above 75 mcg/L as minimum)
- Recheck ferritin at 3 months; continue until target achieved
- IV iron infusion: for patients who do not tolerate oral iron or fail to respond; produces rapid and often dramatic symptom improvement
Other Correctable Causes
- Vitamin D deficiency: associated with RLS in observational studies; supplementation may reduce symptoms
- Magnesium deficiency: GABA-enhancing effect relevant to RLS; 300mg magnesium glycinate at bedtime has trial support
- Medications that can trigger or worsen RLS: antidepressants (particularly SSRIs and TCAs), antihistamines, antipsychotics, antiemetics
- Pregnancy: RLS prevalence is 2 to 3 times higher in pregnancy, partly due to increased iron requirements
Sources
- Allen RP, et al. (2014). Restless legs syndrome/Willis-Ekbom disease diagnostic criteria. Sleep Medicine, 15(8), 860-873.
- Earley CJ, et al. (2014). Abnormalities in CSF concentrations of ferritin and transferrin in restless-legs syndrome. Neurology, 54(8), 1698-1700.
- Trotti LM, Becker LA. (2019). Iron for the treatment of restless legs syndrome. Cochrane Database of Systematic Reviews, 1, CD007834.