Can restless leg syndrome (RLS) progress over time in middle-aged and older adults with a family history of the condition, neurological disorders, iron deficiency, or impaired renal function?

Does Restless Leg Syndrome Progress?

Yes, restless leg syndrome (RLS) can progress over time, particularly in patients with early-onset primary RLS, and although symptoms may remit for various periods, the condition rarely resolves completely once established. 1

Natural History and Progression Patterns

RLS demonstrates variable clinical courses that are formally classified into two patterns:

• Chronic-persistent RLS: Symptoms when untreated occur on average at least twice weekly for the past year, representing the progressive form 1
• Intermittent RLS: Symptoms when untreated occur on average less than twice weekly for the past year, with at least 5 lifetime events 1

The prevalence of RLS clearly increases with age for both men and women, at least until the seventh or eighth decade, with higher rates consistently reported in women compared to men 1. Some of this age-related increased risk occurs because although RLS can develop at any age, it rarely remits 1. This means that once you have RLS, you typically continue to have it, contributing to the higher prevalence seen in older populations.

Factors Contributing to Progression

The increasing prevalence of RLS with age may also occur in association with the increasing presence of secondary causes in the aging population, such as iron deficiency and renal failure 1. This is a critical distinction: the condition itself may progress, but worsening symptoms can also reflect the development of comorbid conditions that exacerbate RLS.

RLS symptoms vary considerably in frequency from less than once a month or year to daily, and severity from mildly annoying to disabling 1. This variable expression is influenced by genetic, environmental, and medical factors 1.

Risk Factors for Progression

Patients with the following characteristics are at higher risk for progressive disease:

• Family history of RLS: A clear familial risk exists for the development of both RLS and periodic limb movements of sleep (PLMS) 1
• Iron deficiency states: Values less than 50 ng/mL are consistent with RLS diagnosis and suggest the need for iron supplementation 1
• Renal failure: End-stage renal disease is associated with RLS, and presence of RLS in hemodialysis patients is associated with higher mortality rates 1, 2
• Neurological disorders: Peripheral neuropathy or radiculopathy may be identified during examination as secondary causes 1

Augmentation: Iatrogenic Progression

A critical form of progression is augmentation, an iatrogenic worsening of RLS symptoms that occurs with dopamine agonist therapy 3. Augmentation is characterized by:

• More intense symptom severity 4
• Earlier symptom occurrence during the day 4
• Symptom spread from the legs to the arms or other body regions 4
• Annual incidence of 7% to 10% with dopamine agonists 5

This is why dopamine agonists are no longer recommended as first-line medications 5, 3.

Clinical Implications

The fact that RLS rarely remits means that long-term management strategies are essential 1. Patients should be counseled that this is typically a chronic condition requiring ongoing treatment and monitoring. However, the variable nature of symptoms—with potential remission periods—means that treatment intensity may need adjustment over time 1.

Regular monitoring of iron studies every 6-12 months is necessary, as brain iron deficiency may persist despite normal serum parameters, and declining iron stores can lead to symptom progression 6.