Elsevier

Sleep Medicine

Volume 5, Issue 3, May 2004, Pages 279-283
Sleep Medicine

Udine Special Section
Restless legs syndrome: an historical note

https://doi.org/10.1016/j.sleep.2004.01.002Get rights and content

Abstract

The article briefly summarizes the milestones leading to current knowledge and the possibility of treating one of the most widespread and perhaps least known diseases, restless legs syndrome (RLS). Until the mid-twentieth century, the syndrome first described by Willis (1685), was sporadically reported in medical literature and in most cases deemed a bizzare condition. It was only with Ekbom’s detailed clinical description of the syndrome (1944) and the polygraphic recordings of Coccagna et al. (1962) that RLS became well-recognised clinical entity. Since then, almost all sleep laboratories have devoted much of their research to discovering the pathogenetic mechanisms underlying the disease and devise increasingly specific treatment. Major advances have been made in recent years, but a full understanding of RLS is still a long way off.

Section snippets

The beginning of the story

In 1685, the great English physician Thomas Willis gave the first unequivocal description of Restless Legs Syndrome (RLS), describing a patient who had difficulty sleeping because of discomfort in the limbs [1]. He wrote: ‘Wherefore to some, when being abed they betake themselves to sleep, presently in the arms and legs, leapings and contractions of the tendons, and so great a restlessness and tossing of their members ensue, that the diseased are no more able to sleep, than if they were in a

Polysomnographic recordings

Coccagna and Lugaresi, having just embarked on the study of sleep disorders, decided that the friar would make an excellent candidate for the investigation of insomnia. A few days later one of them remembered having read an article by Ekbom in Neurology, describing a clinical picture similar to that of the friar and using the term Restless Legs Syndrome [20]. Coccagna offered to follow the sleep recording throughout the night.

At that time, our sleep laboratory had only rudimentary equipment and

The end of the story

When the friar observed that someone had finally taken him seriously and that, for the first time, doctors were interested in his case, he became very cooperative and confessed that his mother and some of his eight siblings had or had had a very similar disorder. We thereafter directly examined six of his eight brothers and contacted another two who had emigrated. All reported a typical history of RLS and confirmed that their mother, who had died in the meantime, had suffered from a severe form

Nocturnal myoclonus and periodic limb movements during sleep

After the friar's first PSG, we routinely began to record the electromyogram of the anterior tibialis muscles in nearly all patients undergoing PSG for any reason. In particular, we had occasion to make a PSG recording of a man whose bed partner complained of his nightly, periodic and regular leg jerks. He was unaware of his disorder and he did not suffer from RLS. The recording disclosed PLMS during light sleep, identical to those found in RLS patients. We published this and other identical

Electrophysiological investigations

In the early 1970s, the Bologna School had completed the clinical and polysomnographic (PSG) definition of RLS. We subsequently performed several electrophysiological studies, demonstrating an impaired excitability curve for the H reflex (a spinal cord reflex) in both RLS and PLMS, more marked during the night, with a slope similar to that found in patients with spasticity. On repeated stimulation the extensor and flexor polysynaptic lower limb reflexes failed to cease, persisting or even

Imaging techniques

Functional imaging studies with SPECT and PET techniques have recently demonstrated a central dopaminergic dysfunction, particularly at the level of the striatonigral system (decreased fluorodopa striatal uptake) in the pathogenesis of the syndrome [31], [32]. This hypothesis is further supported by the beneficial effects of various dopaminergic drugs in the treatment of RLS. Another recent SPECT study demonstrated a decrease in cerebral blood flow in the caudate nuclei and an increase in the

Family studies

Some family studies indicate the possibility that RLS has a strong genetic basis. Members of the RLS study group have examined a number of large pedigrees, including our friar's family, which include many members with RLS. Informal inspection indicates that they are consistent with an autosomal dominant form of inheritance, with variable anticipation and penetrance, suggesting a possible genetic heterogeneity [35].

Treatment

The treatments we advocated for RLS in the early 1970s remain valid today. For the friar and his family, and other sporadic cases of RLS, we demonstrated the efficacy of diazepam in attenuating the sensory disorders when the drug was taken at bedtime. For many years it remained the only treatment available, later replaced by clonazepam. Baclofen, which we also tested, also proved to be effective [36].

Some antiepileptic drugs (gabapentin, carbamazepine, valproic acid) have also given good

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