🩸 Restless Legs Syndrome & Iron Deficiency Simulator

Low Serum Ferritin as the Root Trigger

Peripheral iron stores set the ceiling for brain iron delivery.

• <50: Ferritin threshold (ng/mL RLS risk zone)
• 30–300: Normal range (ng/mL typical adult)
• ~25%: Prevalence link (RLS patients iron deficient)
• Serum ferritin: Screening test (first-line lab check)

Peripheral iron status

Placeholder: low ferritin reflects depleted total-body iron stores.

Brain Iron Depletion in the Basal Ganglia

Regional brain iron tracks peripheral ferritin with a lag.

• Substantia nigra: Key region (iron-rich dopaminergic hub)
• MRI T2*: Imaging marker (detects regional iron loss)
• Transferrin: Transport protein (crosses blood-brain barrier)
• Reduced: CSF ferritin (in RLS patients)

Regional brain iron

Placeholder: basal ganglia iron pools shrink under systemic deficiency.

Iron-Dependent Dopamine Synthesis Falters

Iron is a cofactor for the dopamine-synthesis enzyme pathway.

• Tyrosine hydroxylase: Cofactor enzyme (iron-dependent step)
• Evening worsening: Circadian pattern (matches RLS symptom timing)
• D2 downregulation: Receptor change (postsynaptic adaptation)
• Dopamine agonists: Treatment clue (partially relieve symptoms)

Dopamine pathway disruption

Placeholder: reduced iron impairs dopaminergic neurotransmission.

From Dysfunction to Restless Legs Sensation

Circuit imbalance produces the urge to move the legs.

• Urge to move: Core symptom (worse at rest, evening)
• Movement relieves: Relief pattern (temporary symptom relief)
• Frequent: Sleep disruption (periodic limb movements)
• Clinical criteria: Diagnosis basis (IRLSSG four-point checklist)

Symptom expression

Placeholder: restlessness pulses correlate with dopaminergic deficit severity.

Symptom Improvement with Iron Repletion

Restoring ferritin gradually restores basal ganglia function.

• Oral/IV iron: Therapy route (depends on severity)
• Weeks: Response time (gradual symptom easing)
• >75: Target ferritin (ng/mL treatment goal)
• Reduced severity: Outcome (in responders)

Therapeutic response

Placeholder: iron therapy over weeks lowers RLS severity scores.

Placeholder: sustained iron repletion improves sleep and symptom scores.