Join Date: Aug 2006
Location: New York
The History of Restless Legs Syndrome
Although recognized in the seventeenth century, the modem history of RLS started with the term "restless leg syndrome being coined by Professor KarlAxel Ekbom in 1945 [2,3]. To honor this fact, RLS is also known as 'Ekbom disease'. Ekbom was born in 1907 in Gothenburg in Sweden. He studied medicine at the Karolinska Institute and later became the first professor and head of the department of neurology at Uppsala University Hospital. In his classic 1945 publication  entitled "Restless Legs", Ekbom described the disease and presented eight cases. The addition of the word "syndrome" to the title of the disorder highlights how the disorder is defined by clinical symptoms rather than by a specific pathological process.
Although Ekbom identified and characterized the syndrome of restless legs, he was probably not the first to describe the disease. The earliest documentation of what was very likely to be RLS occurred some 300 years earlier and is credited to the famous English physician, Thomas Willis4 (1621-75), who served King Charles II. The son of a small farmer, he studied at the private school of Edward Sylvester in Oxford and worked in the disciplines of anatomy, physiology, medicine, iatrochemistry and pharmacology. Willis is probably most famous for his publication "Cerebri Anatome : cui Acessit Nervorum Descriptio et Usus", published in 1664, which was a fundamental text on the anatomy of the cerebral system.
As Sedleian Professor at Oxford, Willis lectured on physiology; he also identified diabetes mellitus, meningitis and epidemic typhoid fever (1659). This highly accomplished man, amongst numerous other things, also described a case, in 1672, of what might have been RLS using the current diagnostic criteria. Willis wrote in a chapter entitled "Instructions for curing the Watching evil" in the "London Practice of Physick" (1685):
"... Wherefore to some, when being in bed they betake themselves to sleep, presently in the arms and legs. Leaping and contractions of the tendons and so great a restlessness and tossing of the members ensure, that the diseased are no more able to sleep, than if they were in the place of the greatest torture..."
Willis went on to think that the disease originated in the spinal cord and was a product of spinal irritation and used opiates as his therapy of choice. He wrote:
"Sometimes since I was advised with for a lady of quality, who in the night was hindered from sleep by reason of these spasmodic effects which came upon her only twice a week; she took afterward daily for almost three months, receiving no injury thereby, either on the brain or about any other function, and when while by the use of other remedies; the dyscrasia of the blood and nervous juice being corrected, the animal spirits became more benign and mild. She afterward leaving wholly the opium was able to sleep indifferently well!"
Willis thought that the cure for RLS was bloodletting, but with modern understanding we know that anemia, iron deficiency and/or low ferritin levels can contribute to RLS.
In the nineteenth century the term "anxietas tibiarum" was the name given to the condition in Germany and it was believed to be a form of hysteria, whilst in France the term "impatience musculaire" was adopted.
Descriptions of the disease were also documented by Wittmaak5 in Germany in 1861 as:
"A characteristic feeling is that from older anxietas tibiarum: a strange but descriptive compulsion to move has invaded the legs of the inflicted person. Every moment sees the legs brought into a different position; drawn up, stretched out, abducted, spread apart and crossed over one another However, these movements are not sudden or violent, rather they are slow, mindful as if it were of eventually finding the one position that will give the most relief In every strange description of the nervous tension of hysteria one often also finds this train of involuntary agitation displayed in the legs and feet. The same thing also occurs however else where without one being able to find a definite cause... the condition lasts approximately a quarter of an hour."
Beard  published an article entitled "Neurasthenia, or nervous exhaustion" in the Boston Medical Journal in 1869. He described the disease as "one of the myriad results of spinal irritation", suggesting that the spinal cord might be involved from an early stage. In 1923, Oppenheim was the first to describe RLS as a neurological disorder in his Lehrbuch der Nervenkrankheiten7. His description was also important, as the familial component of the disease was also recognized :
"Restlessness in the legs is a special kind of subjective paralgesia. It can become an agonizing torture, lasting for years or decades and can be passed on and occur in other members of the family."
In 1940, Mussio-Fournier and Rawak described a "curious case" of RLS, entitling the disorder a "familial occurrence of pruritus, urticaria and parasthetic hyperkinesia syndrome of the lower limbs". However, this particular analysis failed to identify the difference between RLS symptoms and an additional allergic disorder which existed concomitantly in this particular family.
Ekbom himself first described the disease in 1944  as:
"Asthenia crurum paraesthetica (irritable legs). A new syndrome consisting of weakness, sensation of cold and nocturnal paraesthesia in legs, responding to a certain extent to treatment with priscol and doryl" .
In a later paper , published in 1945, he wrote:
"A clinical study of a hitherto overlooked disease in the legs, characterized by peculiar paraesthesia, pain and weakness and occurring in two main forms, aestheia crurum paraesthetica and asthenia dolorosa".
The differentiation of RLS in these two phenotypically distinct forms is still valid. The emphasis of the description Ekbom gave of this disorder shifted from the previous preoccupation with the movement abnormality alone to the sensory aspect of the disease. Ekbom had made the distinction that the presentation of the disease could vary, although we know that patients will describe a wide variety of sensations other than the clear-cut `two forms' Ekbom first described.
The link between iron and RLS was formally made in 1953 when Nils Brage Nordlander, a contemporary of Ekbom, put forward the theory that iron insufficiency caused RLS. This differed from Ekbom's emphasis on vascular problems being more important than low levels of iron in the pathogenesis of RLS. Nordlander conducted an open label study on 22 patients and used very large doses of intravenous iron to treat them. Twenty-one of these patients had complete relief from all their symptoms for several months. Of late, most of the pioneering work in relation to iron and RLS has been carried out within the group led by Professor Richard Allen at the Johns Hopkins University, USA 
1. Walters AS. Toward a better definition of restless legs syndrome. The International Restless Legs Syndrome Study Group. Mov Disord 1995;10: 634-42
2. Ekbom KA. Asthenia crurum pasasthetica (irritable legs). Acta Med Scand 1944;118:197-209
3. Ekbom KA. Restless Legs Syndrome. Acta Med Scand 1945:158 (Suppl);4-122
4. Willis T. The London Practice of Physick. London: Basset & Crooke, 1685
5. Wittmaak T Pathologic and Therapie des Sensibilitats-Neurosen. Lehrbuch der Nervenkrankheiten, Ted 1: Pathologie and Therapie der sensiblen Neurosen. Leipzig: E.Schafer 1861
6. Beard GM. Neurasthenia, or nervous exhaustion. Boston MedJ 1869;80:217-21
7. Oppenheim H. Lehrbruch der Nervenkranheiten, 7th edn. Berlin: Karger, 1923: 1774
8. Mussio-Fournier JC, Rawak E Familiares Auftreten von Prurotus. Urtikaria and parasthetischer Hyerkinese der unteren Extremitaten. Confin Neurol 1940;3: 110-15
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10. Strang RR. The symptoms of restless legs. Med J Aust 1967;1:1211-13
11. Nordlander NB. Therapy in restless legs. Acta Med Scand 1953; 143:453-7
12. Allen RP, Barker PB, Wehrl F, et al. MRI measurement of brain iron in patients with restless legs syndrome. Neurology 2001;56:263-5
13. Symonds CE Nocturnal myoclonus. J Neurochem 1953; 16:166-71
14. Lugaresi E, Coccagna G, Tassinari CA, Ambrosetto C. Polygraphic data on motor phenomena in the restless legs syndrome [In Italian]. Riv Neurol 1965;35(6):550-61
15. Coleman R. Periodic movements in sleep (nocturnal myoconus) and restless legs syndrome. In Guilleminault C, ed. Sleeping and Waking Disorders: Indications and Techniques. Menlo Park, CA: Addison-Wesley, 1982:265-95
16. Montplaisir J, Boucher S, Poirier G, et al. Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: a study of 133 patients diagnosed with new standard criteria. Mov Disord 1997;12:61-5