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188 PA R T I I / Physiologic and Pathologic Responses
jerking limb movements either during sleep or while awake and at The carbidopa is a dehydroxylase inhibitor, which decreases the
rest. peripheral breakdown of the levodopa so more can get to the
A related condition, PLMD, was originally termed nocturnal brain. This medication is excellent for patients with sporadic, in-
myoclonus by Symonds in 1953. 182 The periodic nature of the frequent symptoms. However, with chronic use, there is frequent
movements and their common association with RLS were later development of rebound (return of symptoms) or augmentation,
described by Lugaresi et al. 183 and Coleman et al. 184 Periodic limb the tendency for symptoms to develop earlier in the day and/or to
movements (PLMs) usually involve the legs and consist of a sud- be more severe than prior to treatment. In these situations, it is of-
den extension of the great toe (similar to the Babinski reflex) as- ten best to change to a dopamine agonist, in which case the symp-
sociated with flexion at the ankle, knee, and hip. Because the arms toms of rebound and augmentation usually disappear in a few day
are sometimes included, many prefer the term PLMs rather than or weeks. Although dopamine agonists have been traditionally
the previously used term, periodic leg movements. Similar to RLS, used for Parkinson’s disease, several controlled clinical trials have
the expression of PLMs also appears to have a circadian compo- also demonstrated the efficacy of pergolide, 201 pramipexole, 202
nent and is typically worse at night. and ropinirole 203 in the treatment of RLS and PLMD. In fact,
RLS is common and its prevalence is estimated to be between these agents are currently considered first-line drugs for most pa-
5% and 10% in northern European populations, while the preva- tients. Side effects from these medications such as sleepiness, nau-
lence of the disorder in other groups remains to be determined. 10 sea, and hypotension occur infrequently, and can most often be
The disorder can occur at any age, but symptoms often begin in avoided by slowly increasing the dose until symptoms abate.
middle-aged individuals with the mean age of onset being be- Other medications which can be used include opioids (for painful
tween 27 and 41 years. 185,186 However, recent surveys have re- symptoms), anticonvulsants, and benzodiazepines. 204
ported that approximately 40% of RLS patients experienced their
first symptom before the age of 20. 187–190 The disorder is slightly
more common in women. 10 PLMD is also very prevalent, occur- SLEEP IN PATIENTS WITH
ring in up to 6% of the general population and increasing to over CARDIOVASCULAR DISEASE
20% in patients 60 and older.
Both RLS and PLMD occur in idiopathic and secondary Sleep in Coronary Heart Disease (CHD)
forms. The idiopathic form, especially in the case of RLS, is often
found in those who have afflicted first-degree relatives. 191 The ex- Although more than 16 million Americans are estimated to have
act of mode inheritance remains unclear, but the frequency with CHD, 205 their sleep patterns have only recently been studied.
which offspring of affected individuals develop the condition sug- Several recent large studies, such as the Sleep Heart Health Study,
gests an autosomal-dominant genetic pattern. RLS and PLMD have begun to link sleep symptoms and sleep-disordered breath-
may also develop in association with several medical, neurological, ing with risk factors and outcomes of cardiovascular disease. 206
and metabolic conditions and secondary to conditions character- Assessing the independent contribution of sleep to cardiovascular
ized by iron deficiency such as anemia, pregnancy, 192,193 and ure- outcomes is often complicated by confounding variations in age,
mia. 194 Recently, RLS and PLMD in children have been associ- sex, type and severity of cardiovascular impairment, other risk fac-
ated with attention-deficit/hyperactivity disorder 195–197 and tors, and medications. However, growing evidence consistently
cardiovascular disease. 198,199 links sleep disorders with increased cardiovascular risk and sug-
The treatment of RLS and PLMD is symptomatic. Patients gests that patients with coronary heart disease often have dis-
with the mild forms of the disorders may respond favorably to turbed sleep. The magnitude of the sleep disturbance may be the
nonpharmacological interventions. When symptoms are moder- key in that sleep hypopneas with oxyhemoglobin desaturation of
ate to severe, pharmacological therapy is also indicated. at least 4% are independently associated with cardiovascular dis-
Initially, it is important to listen, support, and validate the ex- ease, whereas milder episodes are not. 207
periences of both the patient and family, as they may have gone While mechanisms linking sleep with adverse neurobehavioral
for years with their symptoms and concerns being dismissed by and cardiovascular outcomes are currently being defined, sleep ap-
health care providers. Referral to support groups such as those of- nea and sleep-related disorders are known to contribute to in-
fered through the Restless Legs Syndrome Foundation can help creased CHD risk factors such as hypertension, obesity, inflam-
provide additional support and education. The Restless Legs Syn- matory markers, and metabolic changes related to glucose and
drome Foundation also has a web site with important and relevant insulin. 205,207,208 Thus, during any assessment of cardiovascular
patient and professional information (www.RLS.org). Other non- risk, sleep patterns should be considered and evaluated for contri-
pharmacological interventions that may be beneficial to some pa- bution to other risk factors. The threshold for sleep duration on
tients include hot baths, stretching muscles in the morning and risk factors appears to be a habitual sleep time around less than 5
night, delayed sleep time/rise time, massage, vibration, and mod- to 6 hours per night, or over 9 hours per night. 208,209
erate exercise. 200 The relationship is reciprocal in that impaired cardiac function
Three reversible forms of RLS, including pregnancy, renal fail- from multiple causes can produce symptoms such as chest pain
ure, and anemia, are each characterized by iron deficiency (as re- and dyspnea that interfere with sleep. Even when patients with a
flected in low ferritin levels; 50 and treatment with both oral variety of diseases are considered, cardiovascular symptoms are a
and intravenous iron has been found to improve or resolve RLS major factor associated with symptoms of reduced total sleep and
symptoms. Two types of dopaminergic medications are beneficial increased night-time wakefulness. The psychological impact of
in the treatment of RLS and PLMD. Both decrease symptoms heart disease also has a major impact on sleep. Acute myocardial
and numbers of limb movements. Dopamine precursors, such as infarction (MI), for example, not only affects physical health and
regular or sustained-release carbidopa/levodopa, increase the de- comfort but also influences social relationships, living patterns,
livery of levodopa to the brain where it is converted to dopamine. work options and income, and sense of personal vulnerability.