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Restless Legs Syndrome (RLS) in a Primary Pathic Pain in Addition to RLS

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Restless Legs Syndrome (RLS) in a Primary Pathic Pain in Addition to RLS Restless Legs Syndrome MAX BAYARD, MD; THOMAS aVONDA, MD; and JAMES WADZINSKI, MD, East Tennessee State University, Quillen College of Medicine, Johnson City, Tennessee Restless legs syndrome is a common neurologic movement disorder that affects approximately 10 percent of adults. Of those affected with this condition, approximately one third have symp- toms severe enough to require medical therapy. Restless legs syndrome may be a primary con- dition, or it may be secondary to iron deficiency, renal failure, pregnancy, or the use of certain medications. The diagnosis is clinical, requiring an urge to move the legs usually accompanied by an uncomfortable sensation, occurrence at rest, improvement with activity, and worsening of symptoms in the evening or at night. Restless legs syndrome causes sleep disturbances, is associ- ated with anxiety and depression, and has a negative effect on quality of life. Treatment of sec- ondary causes of restless legs syndrome may result in improvement or resolution of symptoms. Currently, there is little information regarding the effects of lifestyle changes on the symptoms of restless legs syndrome. If medications are needed, dopamine agonists are the primary medi- cations for moderate to severe restless legs syndrome. Other medications that may be effective include gabapentin, carbidopa/levodopa, opioids, and benzodiazepines. (Am Fam Physician. 2008;78(2):235-240, 243. Copyright © 2008 American Academy of Family Physicians.) ▲ Patient information: estless legs syndrome (RLS) is a with RLs than in controls, although serum A handout on restless legs neurologic movement disorder levels were similar between the two groups.7 syndrome, written by the that affects approximately 10 per- Further, serum iron stores (measured by authors of this article, is 1-3 provided on page 243. cent of adults. About one third of serum ferritin) have been shown to correlate Rthose with RLS have symptoms of moderate inversely with RLs severity.8,9 Iron is a cofac- The online version of this article to severe intensity that require medical ther- tor in tyrosine hydroxylase, the rate-limiting includes supple- apy.3 The prevalence of RLS increases with enzymatic step in the conversion of tyrosine mental content at http:// age,1,2 although approximately one third of to dopamine. www.aafp.org/afp. patients with RLS first experience symptoms before 18 years of age. RLS is more common Clinical Evaluation in females.2 There is a genetic predisposition The diagnosis of RLS is clinical. A focused to RLS, which is common in those with early- history and physical examination, as well as a onset RLS. RLS may be a primary condition, laboratory analysis, may identify conditions or it may be secondary to iron deficiency, with similar symptoms or underlying causes pregnancy, renal failure, the use of certain of RLS. The history can reveal valuable infor- medications, or a spinal cord injury. mation, such as: the frequency and severity of symptoms; previous treatments for RLS; cur- Pathophysiology rent medications; family history of RLS; and Research has identified abnormalities in use of caffeine, alcohol, or tobacco. A labora- dopamine and iron function in the central tory analysis is not necessary for the diagno- nervous system in individuals with RLS, sis, but it can help exclude secondary causes although these relationships are not fully of RLS. Initial laboratory tests include a basic understood. Two studies have demonstrated metabolic panel and ferritin level. enhanced circadian variation in dopamine The four diagnostic criteria and three activity in those with RLs compared with supportive criteria for RLS are listed in control patients.4,5 Iron content in the sub- Table 1.10 The differential diagnosis of RLs stantia nigra and the putamen were lower includes nocturnal leg cramps, claudica- in those with RLs than in control patients.6 tion, peripheral neuropathy, and akathisia The levels of ferritin in the cerebrospinal (Table 2). Patients often have a difficult time fluid were significantly lower in patients describing the uncomfortable sensations of Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright © 2008 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. SORT: KEY RECOMMENDATIONS FOR PRACTICE Evidence Clinical recommendation rating References Comments Obtain serum ferritin and consider replacing iron in patients C 9, 14 Expert panel and nonrandomized trial with RLS with ferritin level less than 50 ng per mL (50 mcg per L). Consider changing medications that may exacerbate C 14 Expert panel recommendation symptoms of RLS. If antidepressant therapy is used for patients with RLS, C 14, 16 Expert panel and disease-oriented consider using bupropion (Wellbutrin). data showing decreased PLMS with bupropion compared with SSRIs Dopamine agonists are effective treatment for moderate to A 14, 17-24 Expert advice and RCTs with severe RLS and are the preferred agents for most patients consistent findings with daily RLS symptoms. PLMS = periodic limb movements of sleep; RCT = randomized controlled trial; RLS = restless legs syndrome; SSRI = selective serotonin reuptake inhibitor. A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited quality patient-oriented evidence; C = consensus, disease- oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see http://www.aafp. org/afpsort.xml. RLS. They may complain of crawling, aching, or inde- Children with RLs can be diagnosed using the same scribable feelings in their legs, or they may just have the four criteria as adults (Table 110). In addition, the child need to move. may describe in his or her own words some of the symp- The presence of periodic limb movements of sleep toms consistent with leg discomfort, or have at least two (PLMS) is supportive for the diagnosis of RLS. Approxi- of the following: sleep disturbance, a biologic parent or mately 80 percent of individuals with RLs experience sibling with RLS, or a polysomnographic-documented PLMS, but less than one half of individuals with PLMs PLMs index of 5 or more per hour of sleep.10 also have RLS.10 Effective treatments for RLs typically RLs has a negative impact on quality of life.3 Individu- decrease episodes of PLMS. als with RLs are more likely to be depressed or anxious.3,11 Insomnia and its consequences are common in RLS, with patients having trouble initiat- Table 1. Criteria for Diagnosis of Restless Legs Syndrome ing and maintaining sleep. RLs may be more common in patients Urge to move legs usually accompanied or caused by uncomfortable with Parkinson’s disease than in the general or unpleasant sensations in the legs (urge to move may not be population; however, results from studies of accompanied by uncomfortable sensations, and arms or other body parts may be involved) this correlation are inconsistent and are con- Urge to move or unpleasant sensation begins or worsens during periods founded by concomitant use of dopaminergic 12 of rest or inactivity agents in patients with Parkinson’s disease. Urge to move or unpleasant sensation partially or totally relieved by RLs has not been shown to increase the risk movement (such as walking or stretching) as long as activity continues of developing Parkinson’s disease. Urge to move or unpleasant sensation worse in the evening or at night The severity of RLs symptoms and their than during the day, or only occurs during the evening or at night; in effect on daily life can be assessed using very severe cases, worsening at night may not be noticeable, but must the International Restless Legs Syndrome have been previously present Study Group (IRLSSG) Severity Scale (see Supportive Clinical Features of Restless Legs Syndrome: online Figure A).13 This is a validated, Periodic limb movements 10-question patient survey that can be Positive family history used to quantify the severity of RLs and the Response to dopaminergic therapy patient’s response to therapy. Each answer Adapted with permission from Allen RP, Picchietti D, Hening WA, Trenkwalder C, corresponds to a numerical value from 0 to Walters AS, Montplaisi J, for the International Restless Legs Syndrome Study Group. 4, which is then totaled for all 10 questions. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. a score of 1 to 10 is considered consistent A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003;4(2):102,105. http://www.sciencedirect. with mild RLS; 11 to 20 with moderate RLS; com/science/journal/13899457. Accessed April 1, 2008. 21 to 30 with severe RLS; and 31 to 40 with very severe rLS.13 236 American Family Physician www.aafp.org/afp Volume 78, Number 2 ◆ July 15, 2008 Table 2. Differential Diagnosis of Restless Table 3. Management of Restless Legs Syndrome Legs Syndrome Intermittent RLS* Condition Distinguishing features Nonpharmacologic therapies Akathisia An internal desire to move, most commonly Administer iron replacement in patients who are iron- associated with the use of neuroleptic deficient medications; desire to move not Consider effect of medications that may enhance RLS necessarily associated with discomfort in Recommend mental alerting activities the legs; symptoms are not worse at night
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