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Restless Legs Syndrome

Restless Legs Syndrome

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Published by The Vancouver Sun
Clinical definition of RLS and backgrounder by William Ondo.
Clinical definition of RLS and backgrounder by William Ondo.

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Published by: The Vancouver Sun on Dec 28, 2012
Copyright:Attribution Non-commercial


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Restless Legs Syndrome
Restless legs syndrome (RLS) is clinically defined by the presence of 4 criteria: (1) anurge to move the limbs with or without sensations, (2) worsening at rest, (3) improve-ment with activity, and (4) worsening in the evening or night.
The diagnosis of RLS isexclusively based on these symptoms. A validated diagnostic phone interview,
and quality of life scale
have all been validated based on these features.The patient subjective descriptions, however, are quite varied and tend to besuggestible and education dependent. The sensation is always unpleasant but notnecessarily painful. It is usually deep within the legs and commonly between theknee and ankle. In a study of patients with RLS , the most common terms used, indescending order of frequency, included: ‘need to move,’‘crawling,’‘tingling,’‘restless,’‘cramping,’‘creeping,’‘pulling,’‘painful,’‘electric,’‘tension,’‘‘discomfort,’’ and ‘‘itching.’’
Patients usually deny any ‘‘burning’’ or ‘‘pins and nee-dles’sensations, commonly experienced in neuropathies or nerve entrapments,although neuropathic pain and RLS can coexist. The key is to rephrase their descrip-tion into a question by asking, ‘‘If that makes you want to move your legs, is it betterwhile moving, and are the symptoms worse in the evening/night?’’Essentially all patients report transient symptomatic improvement by walking,although some use stationary bike riding or kicking. Other therapeutic techniquesreported by our patients include rubbing or pressure, stretching, and hot water. Allsymptom relief strategies increase sensory stimulation to the legs and are generallyalerting. Other clinical features typical for RLS include the tendency for symptomsto gradually worsen with age, improvement with dopaminergic treatments, a positivefamily history of RLS, and periodic limb movements of sleep (PLMS).
PLMS are defined by the Association of Sleep Disorders as ‘‘periodic episodes of repetitive and highly stereotyped limb movements that occur during sleep.’The inci-denceinthegeneralpopulationincreaseswithageandisreportedtooccurinasmanyas 57% of elderly people.
Therefore, PLMS are common in the general population.
Department of Neurology, Baylor College of Medicine, 6550 Fannin Drive, Suite 1801, Houston,TX, USA
E-mail address:
Restless legs syndrome
Neurol Clin 27 (2009) 779–799doi:10.1016/j.ncl.2009.04.007
0733-8619/09/$ – see front matter
2009 Elsevier Inc. All rights reserved.
One study, employing a cut-off of 5 PLMS/hour, reported that 81% of patients withRLS showed pathologic PLMS.
The prevalence increased to 87% if 2 nights wererecorded. Although PLMS accompany most cases of RLS, RLS prevalence in thesetting of polysomnographically documented PLMSfound that only 9 of 53 patients(17.0%) with PLMS complained of RLS symptoms.
Therefore, most people withRLS have PLMS but many patients with isolated PLMS do not have RLS. The exactrelationship between the 2 phenotypes is unclear, but recent genetic studies suggestthat they are highly correlated.PLMS can occur simultaneously in both legs, alternate between legs, or occurunilaterally. The duration of movement is typically between 1.5 and 2.5 seconds andvaries in intensity from slight extension of the great toe to a triple flexion response.Other tonic and myoclonic patterns are less frequently observed, and arms areinvolved only in a minority of cases. Patients frequently show a movement periodicityof between 20 and 40 seconds, although wide ranges of frequencies and muscleinvolvement have been reported. Movements are most pronounced in Stage I andStageIIofsleep,wheretheyareoftenaccompaniedbyK-complexesandbyincreasesin pulse and blood pressure.
The K-complexes usually precede the PLMS and maypersist even if PLMS are reduced with
PLMS intensity and frequency lessenas sleep deepens. They may persist during rapid eye movement sleep but both theamplitude and frequency are significantly reduced. PLMS may result in arousals butare not generally associated with insomnia.
RLS in children can be difficult to diagnose.
 Although some children report classicRLS symptoms that meet inclusion criteria, others complain of ‘‘growing pains,’’
and some appear to present with an attention-deficit/hyperactivity disorder (ADHD)phenotype. Kotagal and colleagues
reported that children with RLS have lesserthan expected serum ferritin levels and in most cases appear to inherit the disorderfrom their mother. The National Institutes of Health (NIH) diagnostic criteria for RLSin children are not as well validated but emphasize supportive criteria such as a familyhistory of RLS, sleep disturbances, and the presence of PLMS, which is much lesscommon in pediatric controls.
The exact relationship betweenRLS and ADHD is not known. Children diagnosed with ADHD often have PLMS
and meet some criteria f orRLS.
In children with ADHDtheprevalenceofhavingaparentwithRLS isgreater,
andchildrendiagnosedwithPLMS often haveADHD.
Dopaminergic treatment ofRLS/PLMS in childrenalsoimproves ADHD symptoms.
Therefore, there is clearly some association betweenRLS and ADHD.
In most cases, only a simple evaluation is justified for clinically typical RLS. Serumferritin, and possibly iron-binding saturation, should be obtained for serum iron defi-ciency, and electrolytes should be obtained for renal failure. Nerve conduction veloc-ities (NCV) and electromyogram (EMG) may be performed in cases without a familyhistoryofRLS,atypicalpresentations(ie,sensationsbeginninginthefeetorsuperficialpain), in cases that have a predisposition for neuropathy (ie, diabetes) or when phys-ical symptoms and signs are consistent with peripheral neuropathy. If EMG/NCVabnormalities are found, they should be further evaluated. Polysomnographic evalua-tion is usually reserved for patients in whom the diagnosis is doubtful, in cases wherePLMS are suspected to be severe and result in arousals, or if any other sleep disorder
is suspected. There are several potential diagnostic dilemmas. Akathisia representsan inner sense of restlessness accompanied by an intense desire to move. Thesepatients do not typically complain of limb paresthesia. The restlessness is usuallygeneralized, but may be most prominent in the legs. The condition is usually associ-ated with the use of neuroleptic (dopamine blocking) drugs. Akathisia patients gener-ally have milder sleep complaints and less severe PLMS than is seen in RLS.
 Akathisia tends to be associated with whole-body rocking movements or marchingin place, and it may concurrently show mild extrapyramidal features or tardivedyskinesia.Painful legs and moving toes present with neuropathic leg pain associated withpersistent, semi-rhythmic toe movements, which cannot easily be reproduced voli-tionally, and may be only partially suppressed.
The condition may be associatedwithperipheral nerve injuryorminor leg trauma, butmany patients haveno identifiableetiology or pathology. This syndrome differs clinically from RLS in that the sensorysymptoms are described as painful, are not worsened by immobility, are not neces-sarily worse at night, and are not improved with movement.Nocturnal leg cramps are a common multifactorial disorder manifested by parox-ysmal, disorganized spasms that usually involve the feet or calf muscles. The presen-tation is quite different from that of RLS, but patients may initially describe their RLSsymptoms simply as ‘‘night cramps,’’ which can lead to misdiagnosis if a more exten-sive history is not taken.Other conditions in the differential diagnosis include body positional discomfortsyndrome, where patients simply cannot find a comfortable position to lie in, neuro-pathic or radicular pain, and generalized anxiety.
Historically, epidemiologic studies of RLS were limited by the subjective nature of thedisease,thelackofstandardizeddiagnosticcriteria,andtheindolentonsetofthecondi-tion. Ekbom initially estimated a 5% prevalence of RLS in the general population.
Subsequent general population prevalence surveys varied from 1% to 29%.
Similar to smaller reports, 9.6% of all people met the criteria for RLS. Ingeneral, northern European countries showed increased prevalence compared withMediterranean countries. The vast majority of these persons were not previously diag-nosed, despite frequently reporting symptoms to their physicians.RLS can occur in all ethnic backgrounds; however, most feel that Caucasians aremost affected. While most Caucasian surveys show an approximate 10% prevalence,surveys in Asian populations report much lesser prevalences ( 
 ). People of  African descent have never been specifically studied, but anecdotally African Ameri-cans rarely present with RLS. It is unclear whether this represents a true lesser prev-alence, or rather differences in medical sophistication and referral patterns. Womenusually have higher RLS rates.
In 40%–60% of cases, a family history of RLS can be found, although this is often notinitially reported by the patient.
Twin studies also show a very high concordancerate.
Most pedigrees suggest an autosomal dominant (AD) pattern,
althoughan autosomal recessive (AR) pattern with a very high carrier rate is possible. Todate at least 6 gene linkages have been shown in family studies, 5 risk-factor genesidentified through genome-wide association studies, and 1 through candidate gene
Restless Legs Syndrome

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