Postgraduate Medical Journal (1986) 62, 329-333 Postgrad Med J: first published as 10.1136/pgmj.62.727.329 on 1 May 1986. Downloaded from Review Article The restless legs syndrome W.R.G. Gibb and A.J. Lees National Hospitalsfor Nervous Diseases, Maida Vale, London W9 ITL, UK. The first description of the restless legs syndrome diseases, diabetes, cold exposure or those taking (RLS) is attributed to Thomas Willis in the 'London phenothiazine drugs (Ekbom, 1945, 1950, 1960). A Practice of Physick' of 1685 (Ekbom, 1960). Here he diabetic patient whose symptoms vanished on the side wrote 'wherefore to some, when being a bed they of a recent leg amputation was presented as evidence betake themselves to sleep, presently in the arms and for a peripheral origin (Ekbom, 1961) and Bornstein leggs, leapings and contractions of their tendons, and (1961) speculated about abnormal connections with so great a restlessness and tossings of their members the reticular system. ensue, that the diseased are no more able to sleep than In recent years neuroleptic-induced akathisia has if they were in a place ofthe greatest torture'. In 1861 been compared with idiopathic RLS. Akathisia was Whittmaack used the term anxietas tibiarum to des- originally described in its uncommon idiopathic form cribe nocturnal discomfort of the legs, which he by Haskovec (1901) and later in relation to Parkin- considered was a common symptom of hysteria son syndromes (Sicard, 1923) and drugs such as (Ekbom, 1945). The same phenomenon was called promethazine (Sigwald et al., 1947) and the phenoth- 'impatience musculaire' in the French literature iazines (Steck, 1954). It is characterized by a state of (Ekbom, 1944; Bonduelle, 1952) and the leg jitters by mental and motor restlessness which is accompanied copyright. Allison (1943). by an irresistible compulsion to physically move Ekbom's earliest descriptions of the RLS distingui- about. Restlessness of the legs is common and similar shed a common form which he called 'asthenia crurum to that occurring in idiopathic RLS, but inner restless- paraesthetica' from a painful variant 'asthenia crurum ness of the mind and body is peculiar to akathisia. dolorosa' (Ekbom, 1946). He identified the first of Confusion between these two conditions explains why these in 34 cases. Paraesthesia with deep calf and shin promethazine and prochlorperazine have been con- discomfort started only when the legs were at rest and sidered both cause and ineffective remedy of RLS. http://pmj.bmj.com/ necessitated that they were moved to provide relief. He postulated that pregnancy was an aetiological factor and in some patients he diagnosed prostatitis, testos- Epidemiology terone deficiency and the burning feet syndrome due to malnutrition. Ask-Upmark noted the disorder as a Aches, pains and restless sensations in the legs and late effect of gastrectomy (Ask-Upmark & Meurling, body are at some time an almost universal experience. 1955) and on the basis of anecdotal evidence of RLS may form an extreme example ofthese affections, postural dependence of symptoms, suggested the or could be a different entity. In either case, studies on September 29, 2021 by guest. Protected cause was vascular congestion ofthe spinal cord (Ask- should define the clinical criteria for diagnosis. Sug- Upmark, 1959). Some authors doubted the existence gested criteria are presented in Table I. As a result of ofa distinct syndrome; Purdon-Martin (1946) believed failure to apply definitions, comparable studies of the the symptoms were due to acroparaesthesia and same phenomenon are not reported. Masland (1947) that they were a manifestation of Surveys of 500 and 320 people identified 5% myokymia. (Ekbom, 1960) and 2.5% (Strang, 1967), respectively, By 1960 Ekbom had studied 175 people whom he with symptoms ofrestless legs. It was reported at ages had identified with restlessness of the legs. He found from 7-82 years and in children considered to be in that 5% of normal psychiatrically stable individuals the guise of growing pains (Allison, 1943). In a recent were disturbed by restless sensations, but also believed survey of surgical out-patients personally questioned it was symptomatic of anaemia, certain infectious by the investigators, 8/54 (15%) complained of un- pleasant sensations in the legs associated with an Correspondence: W.R.G. Gibb, M.B., M.R.C.P. inability to keep them still (Braude & Barnes, 1982). Accepted: 2 October 1985 Such a high prevalence is doubted by the authors of a © The Fellowship of Postgraduate Medicine, 1986 330 W.R.G. GIBB & A.J. LEES Postgrad Med J: first published as 10.1136/pgmj.62.727.329 on 1 May 1986. Downloaded from Table I Diagnostic criteria In Parkinson syndrome Ekbom found that 3 of 28 patients had restless legs and Strang found a 7% 1. Discomfort ofboth legs ofa peculiar restless quality. incidence among 600 patients, but presumably none 2. Aching and tension in calfmuscles. were drug-induced (Strang, 1967). According to 3. A desire to shift the legs because ofthe uncomfortable Strang (1967) and Sicard (1923) untreated Parkinson's restless sensation. Other features: disease can be associated with both idiopathic restless movement oflegs provides partial or complete relieffor a legs syndrome and akathisia, although their prevalen- variable period; ces are unknown. reliefby walking is most effective; symptoms are worse in the evenings; occurs in discrete episodes lasting days, weeks or months. Pathogenesis Exclusion criteria: other neurological symptoms or the presence of A peripheral aetiology has often been considered neurological signs; likely. This assumption is based on the peripheral local causes in the legs: nature of the complaints and the absence of a closely dopamine antagonist or depleting drugs; associated neurological disorder or indication of a Parkinsons syndromes. central neurochemical abnormality. However, struc- tural abnormalities in peripheral nerve or muscle have questionnaire based survey of 452 patients of whom not been found to support this concept. The adverse less than 20 complained ofrestless legs (Feest & Read, effects ofanaemia or local ischaemia and the beneficial 1982). When these 20 were interviewed their symptoms effects of movement, vasodilatation and fever were considered non-specific. There is probably no (Ekbom, 1960) once supported the belief that the major sex difference (Morgan, 1967; Sandyk, 1983), disorder was provoked by an excessive accumulation the recent incorporation of twice as many women as of metabolites. men in a study of carbamazepine, may reflect the In a number of patients with leg discomfort and method of selection of patients. This study was based restlessness, nocturnal myoclonic jerks of the limbs in general practice (Telstad et al., 1984). Early studies occur excessively frequently during sleep or relaxation noted that 1/3 to 1/2 of patients reported affected (Frankel et al., 1974; Callaghan, 1966; Thanh et al., copyright. relatives (Ekbom, 1945; Morgan, 1967) and there are 1975). Long recognized as a benign phenomenon examples of familial occurrence (Bornstein, 1961; Oswald (1959) noted nocturnal myoclonic jerks were Boghen et al., 1975; Boghen & Peyronnard, 1976). often linked to an arousal stimulus, suggesting that It is recognized that healthy individuals can be afferent impulses from the legs influenced a susceptible affected, but there have been many suggestions of reticular activating system. During relaxation and the possible causes. These include pica (Ekbom, 1966), onset of sleep an imbalance between inhibitory and late pregnancy, folate-deficiency in pregnancy (Botez excitatory mechanisms in the reticular system allows it & Lambert, 1977), iron deficiency anaemia, blood loss to become susceptible to afferent sensory input. This http://pmj.bmj.com/ (Morgan, 1967), chronic bronchitis, cancer (Ekbom, input precipitates a discharge ofmotor neurones down 1960), neuropathies (Harriman et al., 1979; Gorman et reticulospinal paths. al., 1965, Heinze et al., 1967), venous insufficiency, The recently discovered diencephalo-spinal Parkinson's disease (Morgan, 1967), barbiturate with- dopaminergic system could conceivably be involved in drawal (Gorman et al., 1965), caffeine (Ekbom, 1966), the pathogenesis of restless legs, in neuroleptic-in- a-blockers (Morgan 1975), phenothiazines (Harriman duced akathisia or in the pathology of Parkinson's et al., and depression 1979), anxiety (Morgan, 1967; disease (Lindvall et al., 1983b). It is feasible that there on September 29, 2021 by guest. Protected Gorman et al., 1965). Morgan considered many is an abnormal modulation of sensory information in patients had symptoms considered to be of psy- the dorsal horn involving dopaminergic, noradrener- chosomatic origin such as tension headaches, dyspep- gic or serotinergic neurones. The possibility of altera- sia or proctalgia fugax (Morgan, 1975). Ekbom found tions in muscle tone or abnormal activity at muscle an incidence of 11% in late pregnancy, 24% in iron stretch receptors also remains. deficiency anaemia (Ekbom, 1960) and 12.6% after Akathisia, in contrast, is usually considered to be of gastrectomy (Ekbom, 1966). The aetiological role of central origin because of its association with known neuropathies has not been clarified although it is neurochemical alterations in Parkinson syndrome, described in uraemia (Callaghan, 1966; Thomas et al., neuroleptic therapy and its strong subjective compon- 1971), in alcoholic and diabetic patients (Gorman et ent. Here the most plausible theory