How can I differentiate restless legs syndrome from essential tremor affecting the legs, and what are the appropriate treatments for each?

Differentiating Restless Legs Syndrome from Essential Tremor Affecting the Legs

Restless legs syndrome (RLS) and essential tremor (ET) affecting the legs are fundamentally different disorders that can be distinguished by their core clinical features: RLS is characterized by an irresistible urge to move the legs with relief upon movement, worsening at rest and in the evening, while essential tremor presents as rhythmic involuntary shaking during voluntary movement or posture maintenance without the urge-to-move component.

Key Diagnostic Distinctions

Restless Legs Syndrome Diagnostic Criteria

RLS diagnosis requires all four of the following essential criteria 1, 2:

• An urge to move the legs accompanied or caused by uncomfortable or unpleasant sensations in the legs (often described as crawling, creeping, pulling, or aching) 1, 3
• Symptoms begin or worsen during periods of rest or inactivity, such as sitting or lying down 1, 2
• Symptoms are partially or totally relieved by movement, such as walking or stretching, for at least as long as the activity continues 1, 2
• Symptoms are worse in the evening or night than during the day 1, 2

The physical examination in primary RLS is typically unremarkable 1. RLS can be conceptualized medically as a "movement-responsive quiescegenic nocturnal focal akathisia usually with dysesthesias" 2.

Essential Tremor Characteristics (When Affecting Legs)

Essential tremor affecting the legs presents with:

• Rhythmic, involuntary oscillatory movements that occur during voluntary muscle contraction or posture maintenance 3
• No urge to move or uncomfortable sensations that compel movement 3
• Tremor is visible and measurable on examination, unlike the subjective sensations of RLS 3
• Symptoms are action-induced or postural, not rest-induced 3
• No circadian pattern—symptoms do not worsen specifically in the evening 3
• Movement does not provide relief; rather, tremor occurs during movement or sustained posture 3

Critical Differential Diagnosis Points

The single most distinguishing feature is the urge to move: RLS patients have an overwhelming compulsion to move their legs to relieve discomfort, while ET patients have involuntary shaking without any urge 2.

Timing patterns differ fundamentally: RLS worsens with inactivity and in the evening/night 1, 2, whereas ET has no circadian variation and worsens with action 3.

Response to movement is opposite: RLS improves with movement 1, 2, while ET is present or worsened during movement 3.

Common RLS Mimics to Exclude

The differential diagnosis for RLS includes 1:

• Peripheral neuropathies (constant symptoms, not relieved by movement, no circadian pattern)
• Vascular disease/intermittent claudication (pain with walking, relieved by rest—opposite of RLS)
• Neuroleptic-induced akathisia (medication history, generalized restlessness)
• Arthritides (joint-specific pain, worse with movement)
• Nocturnal leg cramps (sudden, painful muscle contractions, not an urge to move)

A thorough neurologic examination is essential to identify secondary causes such as peripheral neuropathy or radiculopathy 1.

Appropriate Treatment for Restless Legs Syndrome

Initial Assessment and Iron Management

Before initiating any pharmacologic therapy, check morning fasting serum ferritin and transferrin saturation after avoiding iron-containing supplements for at least 24 hours 4.

• Iron supplementation is indicated if ferritin ≤75 ng/mL or transferrin saturation <20% (higher thresholds than general population guidelines) 4
• Oral ferrous sulfate 325 mg daily is conditionally recommended 4
• IV ferric carboxymaltose 750-1000 mg is strongly recommended for patients who cannot tolerate oral iron or fail oral therapy 4

First-Line Pharmacologic Therapy

The American Academy of Sleep Medicine strongly recommends alpha-2-delta ligands (gabapentin, gabapentin enacarbil, or pregabalin) as first-line therapy for RLS with moderate certainty of evidence 4, 5. This represents a major shift from older guidelines that recommended dopamine agonists.

Gabapentin dosing:

• Start 300 mg three times daily 4
• Titrate by 300 mg/day every 3-7 days 4
• Target maintenance dose: 1800-2400 mg/day divided three times daily 4
• Maximum studied dose: 3600 mg/day 4

Pregabalin offers twice-daily dosing with potentially superior bioavailability 4.

Medications to Avoid or Use with Extreme Caution

The American Academy of Sleep Medicine suggests against the standard use of dopamine agonists (pramipexole, ropinirole, rotigotine) due to a 7-10% annual risk of augmentation—a paradoxical worsening of symptoms with earlier onset, increased intensity, and spread to other body parts 4, 5.

The following agents receive strong recommendations against use 4:

• Cabergoline (cardiac valvular fibrosis risk)
• Bupropion
• Carbamazepine
• Clonazepam (provides only sedation, does not reduce periodic limb movements)
• Valproic acid (hepatotoxicity and teratogenicity)

Second-Line Options for Refractory Cases

For moderate to severe refractory RLS after optimizing iron status and trialing alpha-2-delta ligands 4:

• Extended-release oxycodone and other low-dose opioids (methadone 5-10 mg daily, buprenorphine) are conditionally recommended 4
• Long-term studies show relatively low abuse risk with only small dose increases over 2-10 years in appropriately screened patients 4
• Bilateral high-frequency peroneal nerve stimulation is a non-pharmacological option with conditional recommendation 4

Lifestyle Modifications

Address potential exacerbating factors 4:

• Eliminate alcohol, caffeine, and nicotine, especially in the evening 4
• Discontinue antihistaminergic medications, serotonergic medications, and antidopaminergic medications when possible 4
• Treat untreated obstructive sleep apnea 4

Appropriate Treatment for Essential Tremor Affecting the Legs

Essential tremor treatment is fundamentally different from RLS and typically involves 3:

• Beta-blockers (propranolol) as first-line therapy
• Primidone as an alternative first-line agent
• Topiramate or gabapentin for refractory cases
• Botulinum toxin injections for localized tremor
• Deep brain stimulation for severe, medication-refractory cases

None of the RLS treatments (dopamine agonists, alpha-2-delta ligands for RLS indication, iron supplementation) are appropriate for essential tremor 3.

Critical Pitfalls to Avoid

• Do not diagnose RLS without all four essential criteria being met—partial fulfillment suggests a mimic 1, 2
• Do not use dopamine agonists as first-line therapy for RLS given current evidence of high augmentation risk 4, 5
• Do not assume normal serum ferritin means adequate iron stores for RLS—the threshold is ≤75 ng/mL, not the general population cut-off 4
• Do not increase dopamine agonist doses if augmentation is suspected—this worsens the condition 1, 4
• Do not confuse the visible, rhythmic shaking of essential tremor with the subjective urge to move in RLS 3, 2
• Do not treat essential tremor with RLS medications or vice versa—the pathophysiology and treatment paradigms are completely different 4, 3