Enr J Vasc Endovasc Surg 14, 430-432 (1997)

REVIEW ARTICLE

Restless Legs Syndrome - A Review

H. J. S. Jones and J. K. Derodra

Department of Vascular Surgery, Mayday University Hospital, London Road, Thornton Heath, Surrey CR7 7YE, U.K.

Restless legs syndrome is also known as Ekbom's syndrome, following his description in 1944, although the earliest known description dates from 1685 (Willis). It is a fairly common complaint which is not widely recognised by the medical profession. It gives the sufferer an unpleasant sensation in the legs at rest, causing an irresistible desire to move, which alleviates the discomfort.

Key Words: Restless legs syndrome; Ekbom's syndrome.

Incidence

Restless legs syndrome (RLS) affects 5% of the popu- lation. Both males and females are affected, but those with severe symptoms are usually female. ~'2 The syn- drome can occur at any age, but is more common in the elderly, s Certain groups who have a higher in- cidence have been identified, and these include patients presenting to surgical outpatient clinics, and particularly those presenting with varicose veins (15- 22%4'5), pregnant women 6 and dialysis patients. 7 Some families show a familial tendency, ~ with an autosomal dominant pattern of transmission. RLS has been as- sociated with a large number of conditions, including anaemia, deficiencies of iron, folic acid and mag- nesium, uraemia, rheumatoid arthritis, amyloidosis, carcinoma, stress and depression, chronic lung disease, caffeine and a number of drugs. 1'7-1° RLS is a common cause of insomnia. ~

Aetiology and Pathogenesis

Despite the vast number of conditions reported to be associated with RLS, there are no proven aetiological factors. Metcalfe et al. ~1 presented two possible theories

Address correspondence to: J. K. Derodra.

Table 1. Diagnostic criteria for Restless Legs Syndrome.

Sensations occur only at rest Worse during evening and early night Cause irresistible urge to move legs Felt deep inside legs, not in skin

to explain the symptoms: the vascular and the neuro- pathic. The vascular theory postulates an impairment in the local circulation, causing ischaemia or a build- up of toxic metabolites. The associations with varicose veins and anaemia are thought to support this theory, as is the relief which may be obtained by movement, fever and vasodilators, which all increase local blood flOW.

The neuropathic theory suggests a minor ab- normality in the central nervous system, possibly in the EEG 3's or in the dopaminergic or endogenous opioid pathways. 12'~3 Other movement disorders, such as Parkinson's disease and Tourette's syndrome, may be caused by an imbalance in central neuro- transmitters, and dopaminergic and opioid drugs can be effective therapy for restless legs. The relief of symptoms produced by movement or rubbing may be due to the afferent sensory input effect. In view of the association with varicose veins, Kanter 5 has suggested that microcirculatory changes in the small superficial veins may cause restless sensations by stimulation of afferent nerve fibres. EMG and nerve conduction studies, nerve and muscle biopsies have not shown any consistent abnormality.

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Restless Legs Syndrome 431

Table 2. Treatment regimens for Restless Legs Syndrome.

Reassurance Varicose veins - sclerotherapy or surgery Drugs

Benzodiazepines e.g. Clonazepam i mg nocte

Dopaminergic agents e.g. Madopar (benserazide ÷ levodopa) 62.5-250 mg nocte

Others e.g. Quinidine, Chlorpromazine, Sodium valproate, Paroven

Clinical Features

There is an unpleasant sensation felt deep inside the legs, often described as a "creeping" or "crawling" sensation. This occurs at rest, usually in the evening and night, and is worse after a tiring day. It causes an irresistible urge to move the legs, often by getting up and walking around, which relieves the sensation but may seriously disturb the sleep pattern of the sufferer. Symptoms are usually bilateral, and felt in the calves (Table 1), but if severe may involve the feet, thighs and even the arms. Many sufferers also have periodic leg movements during sleep. 14

RLS is a chronic condition, with alternating periods of exacerbation and remission, but no obvious factors to explain the variation. The majority of sufferers have only mild symptoms, but those who are severely affected may develop symptoms whenever at rest, making them unable to sit still for any length of time, with adverse effects on their work and social activities, as well as sleep disturbances, which may result in anxiety and depression.

Treatment

There is no really effective treatment for RLS. In mild cases, no treatment is required, and simple measures such as massage and movement may help. Re- assurance and advice to decrease tiring activity is often beneficial. For those with varicose veins, injection sclerotherapy has been shown to be very effective in alleviating restlessness in the short-term, and has the advantage of avoiding long-term medication. 5

Many drugs have been tried, none with consistent success. Ekbom 1 noted that "a certain medicine seems to be helpful for a time but is subsequently ineffective". Montplaisir et al. 14 reviewed the three main groups of drugs used. These are benzodiazepines, in particular clonazepam, which is the initial treatment of choice, especially in the young; opioids, which are effective in some patients, but carry the risk of abuse and addiction; and dopaminergic agents such as levodopa, bromocriptine and selegiline, which have the side effects of an increase in symptoms during the dayt ime following an evening dose and insomnia, due to an alerting effect.

A number of other drugs have been used, including quinine, vitamins, iron 1 and folic acid al though no controlled studies have shown them to be effective (Table 2). Vasodilators, 1 clonidine 15 and carbamaz- epine 16 have also been tried. The rutoside Paroven has a therapeutic effect in restless legs associated with varicose veins, 17 which may be due to an increased oxygen level in the blood, or to decreased interstitial fluid pooling as a result of reduced capillary per- meability. I1,~8

Diagnosis

Diagnosis is based on the typical history, as there are no consistent findings on examination or investigation. Ekbom 1 stated that the following criteria are required for diagnosis: the sensations appear only at rest, are felt deep inside the legs, not in the skin, occur most often in the evening and early part of the night, and produce an irresistible need to keep the legs moving. In a patient presenting with restless legs, a blood test to exclude iron-deficiency anaemia and uraemia is worthwhile, in view of the association with these conditions. It is important to exclude any other cause of the symptoms, especially in the case of sudden onset of severe symptoms, when a psychiatric disorder, a neurological disorder such as multiple sclerosis, or a drug reaction may be responsible.

Conclusion

Restless legs syndrome is often ignored by the medical profession, probably because of the absence of both a clear explanation for the symptoms, and an effective treatment. For many, who have only minor symptoms, recognition of the syndrome and reassurance may considerably alleviate their suffering, but can only be given if the doctor is aware of the syndrome. We therefore suggest that it is important to increase aware- ness of this condition among doctors.

References

1 EKBOM KA. Restless legs syndrome. Neurology 1960; 10: 868-873. 2 WILLIS T. The London Practice of Physick. London: Thomas Basset

and William Crook 1685: 404.

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432 H . J . S . Jones and J. K. Derodra

3 MONTPLAISIR J, LAPIERRE O, LAVIGNE G. Le syndrome d'im- patiences musculaires: une maladie associ6e au ralentissement p6riodique ou ap6riodique de I'EEG. Neurophysiol Clin 1994; 24: 131-140.

4 BRAIdDE W, BARNES T. Clonazepam: effective treatment for rest- less legs syndrome in uraemia. Br Med J 1982; 284:510 (letter).

5 KANTER AH. The effect of sclerotherapy on restless legs syn- drome. J DermatoI Surg Oncol 1995; 21: 328-333.

6 GOODMAN JDS, BRODIE C, AYIDA GA. Restless leg syndrome in pregnancy. Br Med J 1988; 297: 1101-1102.

7 READ DJ, FEEST TG, NASSIM MA. Clonazepam: effective treatment for restless legs syndrome in uraemia. Br Med J 1981; 283: 885-886.

8 poPovicIu L, ASGIAN B, DELAST-PoPovIcIU D, ALEXANDRESCU A, PETRUTIU S, BAGATHAI I. Clinical, EEG, electromyographic and polysomnographic studies in restless legs syndrome caused by magnesium deficiency. Rom J Neurol Psychiat 1993; 31: 55-61.

9 CYBULSKA E, RUCINSKI J. Restless legs syndrome. Br J Hosp Med 1985; 34: 370-371.

10 REYNOLDS G, BLAKE DR, PALL HS, WILLIAMS A. Restless leg syndrome and rheumatoid arthritis. Br Med J 1986; 292: 659-660.

11 METCALFE RA, MACDERMOTT N, CHALMERS RJG. Restless red legs: an association of the restless legs syndrome with arborising telangiectasia of the lower limbs. J Neurol Neurosurg Psychiatry 1986; 49: 820-823.

12 MULLER N, VODERHOLZER U, KURTZ G, 8TRAUBE A. Tourette's syndrome associated with restless legs syndrome and akathisia in a family. Acta Neurol Scand 1994; 89: 429-432.

13 O'SULLIVAN RL, GREENBERG DB. H2 antagonists, restless leg syndrome, and movement disorders. Psyehosomatics 1993; 34: 530-532.

14 MONTPLAISIR J, LAPIERRE O, WARNES H, PELLETIER G. The treatment of the restless leg syndrome with or without periodic leg movements in sleep. Sleep 1992; 15: 391-395.

15 I-IANDWERKER JV, PALMER RE. Clonidine in the treatment of "restless leg" syndrome. N Engl J Med 1985; 313: 1228-1229.

16 TELSTAD W~ SORENSEN O z LARSEN S, LILLEVOLD PE, STENSRUD Pr NYBERG-HANSEN R. Treatment of the restless legs syndrome with carbamazepine: a double blind study. Br Med J 1984; 288: 444-446.

17 BALMER A, LIMONI C. Klinische, plazebokontrollierte Dop- pelblindprufung yon Venoruton bei der Behandlung der chron- isch venosen Insuffizienz. Die Bedeutung der Patientenauswahl. Vasa 1980; 9: 76-82.

18 McEwAN AJ, MCARDLE CS. Effect of hydroxyethylrutosides on blood oxygen levels and venous insufficiency symptoms in varicose veins. Br Med J 1971; 2: 138-141.

Accepted 9 May 1997

Eur J Vasc Endovasc Surg Vol 14, December 1997