Restless Legs Syndrome (RLS) as the Most Likely Diagnosis
Your relative's inability to sit still, fidgetiness, and restlessness most likely represents Restless Legs Syndrome (RLS), a neurological disorder characterized by an irresistible urge to move the legs, typically worsening with rest and in the evening. 1
Diagnostic Criteria to Confirm RLS
To establish this diagnosis, your relative must meet all five essential criteria 1:
- Urge to move the legs - Usually accompanied by uncomfortable sensations (described as creepy-crawly, burning, itching, or painful feelings) 1
- Symptoms begin or worsen with rest - Sitting or lying down triggers or intensifies the discomfort 1
- Relief with movement - Walking, rubbing, or stretching provides at least partial relief while the activity continues 1
- Circadian worsening - Symptoms are worse in the evening or at night compared to daytime 1, 2
- Not better explained by another condition - Must rule out leg cramps, arthritis, venous stasis, positional discomfort, or habitual foot tapping 1, 3
Critical distinction: If your relative describes muscle tightening/cramping that is relieved specifically by stretching the affected muscle (not general movement), this would instead suggest nocturnal leg cramps rather than RLS 3.
Essential Clinical Evaluation
History Questions to Ask
Ask your relative these specific questions 3:
- "What does it feel like?" (dysesthesias vs. muscle tightening)
- "Is it relieved by any movement or only stretching?" (RLS vs. cramps)
- "When does it occur?" (evening/night worsening suggests RLS)
- "Can you sit through a movie or long car ride?" (RLS patients typically cannot) 1
Physical Examination Priorities
A thorough neurological examination is essential to identify secondary causes 1:
- Peripheral neuropathy signs - Check for sensory deficits, abnormal reflexes 1, 3
- Vascular assessment - Palpate pulses to rule out intermittent claudication 3
- Venous examination - Look for varicosities 3
The physical exam is typically unremarkable in primary RLS, but abnormalities point toward secondary causes 1.
Laboratory Testing
Obtain serum ferritin - This is the single most important test 1, 4:
- Values <50 ng/mL are consistent with RLS and indicate need for iron supplementation 1, 4
- Some experts recommend supplementation when ferritin ≤75 ng/mL 5, 6
- Also check transferrin saturation; <20% warrants iron replacement 5, 6
No polysomnography is needed for diagnosis in typical cases 1, 3. Reserve sleep studies only if periodic limb movement disorder is suspected or diagnosis remains unclear 3.
Common Conditions That Mimic RLS (Differential Diagnosis)
Nocturnal Leg Cramps
- Pain is muscle tightening, not dysesthesias 3
- Relief comes from stretching the specific muscle, not general movement 3
- No urge to move when cramp is not occurring 3
Akathisia (Medication-Induced)
- Caused by antipsychotic medications or dopamine antagonists 1
- Presents as severe restlessness and pacing 1
- Lacks the circadian pattern of RLS (not worse at night) 1
- Often misinterpreted as psychotic agitation 1
Anxiety Disorders
- Fidgetiness and restlessness can occur with anxiety 1
- However, anxiety-related restlessness lacks the sensory component (uncomfortable leg sensations) 1
- Not specifically relieved by leg movement 1
- May have other anxiety symptoms: worry, fear, hypervigilance 1
Peripheral Neuropathy
- Can cause leg discomfort but symptoms are constant, not worse with rest 1, 3
- Sensory deficits on examination 1
Underlying Causes to Investigate
Medications That Worsen RLS
Immediately review and consider discontinuing 1, 4, 5:
- Tricyclic antidepressants
- SSRIs (selective serotonin reuptake inhibitors)
- Lithium
- Dopamine antagonists/antipsychotics
Medical Conditions Associated with RLS
- Iron deficiency (most common, check ferritin) 4
- Renal failure (end-stage renal disease strongly associated) 4, 2
- Pregnancy (if applicable) 4, 2
Lifestyle Factors That Contribute
Address modifiable risk factors 1, 4:
- Increased caffeine intake
- Tobacco use
- Sedentary lifestyle
- Elevated body mass index
Treatment Approach
First-Line: Iron Supplementation (If Indicated)
If ferritin <50 ng/mL (or ≤75 ng/mL by some guidelines) 1, 4, 5:
- Start ferrous sulfate as first-line oral iron 1, 5
- Consider IV iron formulations for severe cases or malabsorption 5
First-Line: Pharmacologic Therapy
Alpha-2-delta ligands are strongly recommended as first-line 1, 5, 6:
- Gabapentin, gabapentin enacarbil, or pregabalin 1, 6
- These are preferred over dopamine agonists because they avoid augmentation (a complication where symptoms worsen and occur earlier in the day) 1, 5, 6
Dopamine agonists remain an option but should be used at the lowest effective dose due to augmentation risk 1, 6:
- Examples: pramipexole, ropinirole 2, 6
- Reserve for cases where alpha-2-delta ligands are ineffective or not tolerated 6
Non-Pharmacologic Measures
Recommend for all patients 7:
- Good sleep hygiene
- Avoidance of alcohol, caffeine, and nicotine
- Regular moderate exercise (but not excessive, which can worsen symptoms)
- Leg massage or warm baths before bed
Critical Pitfalls to Avoid
Do not assume electrolyte abnormalities cause the symptoms - This is poorly supported and leads to unnecessary testing 3
Do not confuse RLS with nocturnal leg cramps - This leads to inappropriate dopaminergic therapy when simple stretching would suffice 3
Do not overlook iron supplementation even when ferritin appears "normal" by general standards - RLS requires higher thresholds (≥50-75 ng/mL) due to brain iron deficiency 1, 4, 5
Do not start dopamine agonists without considering augmentation risk - Alpha-2-delta ligands should be first-line to avoid this complication 1, 5, 6
In cognitively impaired individuals, look for behavioral signs: rubbing/kneading legs, groaning while holding legs, pacing, repetitive foot tapping, inability to remain seated 1
Do not order polysomnography routinely - Diagnosis is clinical based on history; sleep studies are unnecessary in typical cases 1, 3