RESTLESS LEG SYNDROME
H. Compton Gift, M.D., M.P.H.
WEEK 16
“Sleep and watchfulness, both of these when immoderate constitute disease”
Hippocrates
Learning Objectives:
1. Discuss the symptoms and diagnostic criteria of RLS.
2. Describe the pathophysiology and epidemiology of RLS.
3. Identify common non-pharmacologic and pharmacologic management strategies.
Author’s Note:
It was challenging to find a single review article that comprehensively covers this topic
from the point of view of a Primary Care Practitioner. I have included two that for me
highlight the important issues of diagnosis (Stiasny et al) and management (Earley) of
RLS.
CASE ONE:
Mr. Ian Somnia is a 58-year-old man with a history of diabetes and chronic kidney disease
on dialysis who presents with a complaint of a creeping feeling deep inside his legs that is
most bothersome when he lies down. The sensation improves if he massages his calf.
Often, he must get out of bed and walk for complete relief. You suspect restless leg
syndrome.
Questions:
1. What other historical facts may help in confirming your diagnosis, and are there
other possible explanations for his complaint?
Patients with RLS often have difficulty describing their sensory symptoms, which are
usually unpleasant, but not painful. The sensations usually occur below the knees, and
common terms used to describe the feeling include pulling, tension, nervousness,
cramping, or “like insects crawling inside my legs.” Table I in the Stiasny et al. article
provides a list of the features necessary for the diagnosis of RLS.
Other pertinent history would include the use of caffeinated beverages or alcohol at
bedtime, his current medication use, especially beta-blockers, SSRI’s, phenytoin and
neuroleptics, such as olanzapine and risperidone, which can worsen or induce RLS.
CASE ONE CONTINUED:
His physical exam is remarkable for a normal neurological examination.
2. What diagnostic studies might be indicated?
More than 75% of the cases of RLS are idiopathic, however, a number of disorders have
clearly been associated with RLS, including iron deficiency, diabetes and end-stage renal
disease. The relationship between iron and RLS is perhaps the most studied. Iron
deficiency has been implicated in neurologic compromise, including motor impairment
and cognitive deficits. The Stiasny article proposes an explanation for the circadian
rhythm of RLS, based on the circadian rhythm of serum (CSF) iron. A study of brain iron
concentration using MRI found significantly reduced iron in the subsantia nigra (Connor
et al. Neurology 2003, 61:304). Most authors suggest serum ferrokinetic studies, even in
the absence of anemia.
CASE ONE CONTINUED:
Lab evaluation is unremarkable except for anemia.
3. What management strategies might be offered him?
A number of non-pharmacologic and pharmacologic interventions can be suggested
(Table 2 in Earley NEJM).
a. Sleep Hygiene:
 Lifestyle modifications
 Avoidance of heavy meals, caffeine, and alcohol in the evening
 Fixed bedtimes and wake times
 Use of the bedroom for sleep or intimacy
b. Insure appropriate iron stores with repletion of serum ferritin to a level above50
mg and Fe saturation above 20%.
c. Drugs
The general approach is to use dopamimergic drugs as first line therapy. The
nonergotamine dopamine agonists pramipexole and Ropinirole are favored
because of their limited side effect profile (nausea, light headedness, and fatigue).
Benzodiazepines and opioids have been used in patients who fail to respond to the
dopamine agonists. Benzos are also useful in mild cases of RLS. Occasionally,
the addition of antiepileptics, especially the use of gabapentin, among dialysis
patients has proven beneficial. It is important to note that the use of a
pharmacologic agent to treat RLS is symptomatic and not curative.
CASE ONE CONTINUED:
Given Mr. Ian Somnia’s history of dialysis and anemia, you elect to start him on oral iron
and pergolide (safer in ESRD). After supplementation of his iron stores, his symptoms are
not improved, and six months later he reports involvement of his upper extremities and
that now he experiences this creeping sensation in the early evening.
4. What may possibly explain his course of RLS?
Augmentation and rebound are not unusual phenomena with drug treatment.
Characteristically, there is an increase in symptom severity and involvement of other
limbs. Symptoms shift from bedtime to early evening or daytime.
The management consists of adding a middle of the night dose of drugs, switching to one
with a longer half-life.
CASE TWO:
A 36-year-old pregnant woman is referred to you from the OB Clinic because of a
“funny creepy sensation” in her legs that is prominent at night and requires that she get
up and walk for a while for relief. You note that Mr. Somnia is her older brother.
5. Discuss your approach for the diagnosis and management of RLS in her case.
Up to 20% of women during pregnancy report symptoms of RLS. It is important,
however, not to ignore other etiologies, such as those affecting her brother, e.g. anemia
and diabetes.
When considering pharmacotherapy in the pregnant patient, in addition to iron and
folate supplementation, pergolide is the only dopamine agonist that is category B. All
others fall into category C.
References:
1. Earley, C.J. Restless legs syndrome. New England Journal of Medicine. 2003; 348;
2103-9.
2. Stiasny K. et al. Clinical symptonatology and treatment of restless legs syndrome and
periodic limb involvement disorder. Sleep Medicine Rev. 2002. (6): 253-265.
Additional References:
1. Tarsy and Sheon. Restless Legs Syndrome Up-to-date. April 2004
2. Phillips B et al. Epidemiology of Restless Legs Symptoms In Adults. Arch Intern Med,
2000; 160:2137-41.
3. Connor JR, et al. Neuropathological examination suggests impaired brain iron acquisition
in restless legs syndrome. Neurology. 2003;61(3):304-9.
4. Krieger J and Schroeder C. Iron, brain and restless legs syndrome
Sleep Medicine Reviews 2001;5(4):277-286.
5. Rama A. and Kushida C. A Practical Approach to Recognizing and
Managing Restless Legs Syndrome, Medscape Feb. 26 2004.