RLS is a neurological d/o that is often undiagnosed and untreated despite being common
Also called Willis-Ekbom disease
Causes both sleep initiation and sleep maintenance problems
Dx criteria (all required)
- Urge to move body parts, usually legs, with uncomfortable sensations
- Sx start or worsen during rest or immobility
- Movement gives partial or temporary relief
- Sx worse in the evening and night
- Sx not solely explained by another condition, e.g. cramps, positional discomfort, myalgia, venous stasis
Supportive criteria: Family hx of RLS in 1st-degree relatives, Response to dopaminergic drugs, Presence of PLMS
PLMS and PLMD: PLMS occur in up to 90% of RLS pts
PLMS def: each movement 0.5-10 sec, 5-90 sec apart, ≥4 in a series
PLMD requires PLMS index >15/hr in adults, >5/hr in children
Epidemiology: RLS prevalence 2-15% of adults, PLMS seen in 1/3 of pts >60 yrs
Associated conditions
- Pregnancy (up to 26% of women)
- Iron deficiency
- Uremia
- Peripheral neuropathy, esp small fiber
- Myelopathy: MS, syringomyelia, cord tumors
- Other neuro d/o: Parkinson’s dz, spinocerebellar ataxias, essential tremor
Clinical features
Pt descriptions vary: pulling, jittering, itching, bubbling, insects under skin, electric, tightness, throbbing, tingling
Legs most common, can involve arms, abdomen, chest, genitalia, face
May present only as sleep initiation insomnia, careful hx needed
Bed partner may report twitching or jerking in sleep
Often confused with fatigue syndromes, depression or other sleep d/o
Pathophysiology
Not fully understood, dopaminergic dysfunction is the leading hypothesis
Increased dopamine in substantia nigra with postsynaptic receptor downregulation alters spinal network activity
Iron is a cofactor in dopamine production, explains role of iron deficiency and iron tx
Strong genetic component, heritability 50-80% in twin studies
GWAS have identified several gene variants linked to RLS and PLMS
Workup
85% of RLS and PLMD pts do not need meds
Identify aggravating behaviors: sleep restriction, alcohol, caffeine, nicotine
Stop triggering meds if possible:
a. Dopamine blockers (antipsychotics, antiemetics)
b. Beta blockers and CCBs
c. Antihistamines
d. Antidepressants
Renal profile to rule out uremia
Iron studies, esp ferritin
AASM 2024: oral iron if ferritin ≤75 and/or TSAT <20%
AASM 2024: IV iron if ferritin ≤100 and TSAT <45%
Treatment
Non-pharm: Optimize sleep hygiene, consider CBT-I, Relaxation therapy, Walking or stretching before bed, Massage of affected areas, Warm bath before bed
Pharm
AASM 2024: alpha-2-delta ligands and IV iron are 1st line, dopamine agonists no longer recommended for standard use
Alpha-2-delta ligands
Gabapentin and pregabalin (off-label), gabapentin enacarbil is FDA approved
No augmentation or impulse control d/o
Max nighttime dose: pregabalin 300 mg, gabapentin 900 mg
IV iron: AASM 2024: strong recommendation for IV ferric carboxymaltose
Dopamine agonists
Ropinirole, pramipexole, rotigotine are licensed for RLS
Side effects: nausea, grogginess, orthostatic hypotension
Augmentation: worsening of RLS beyond natural course, esp at higher doses
Use lowest effective dose
US labeled max: ropinirole 4 mg, pramipexole 0.75 mg, rotigotine 3 mg daily
Impulse control d/o: compulsive eating, gambling, shopping, hypersexuality
Caution with hx of substance use or psych d/o
Other
Clonazepam: standard off-label tx, esp with comorbid insomnia, start 0.25-0.5 mg qhs
Methadone used in extreme cases
AASM 2024 also supports dipyridamole and bilateral peroneal nerve stimulation (conditional)
PLMD tx
Isolated PLMD tx less evidence based, no licensed tx
PLMS not always linked to sleep complaints
Treat if prominent sleep maintenance insomnia or daytime sx, using RLS options
- Oxford Handbook of Sleep Medicine 2022