General Introduction: Restless Legs Syndrome as a Neurological Conundrum

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Chapter 1 General Introduction: Restless Legs Syndrome as a Neurological Conundrum

Restless legs syndrome (RLS) is among the most common neurological conditions affecting the general population. As described in Chapter 6 of this book, a number of epidemiological studies in Europe and North America have yielded consistent findings of RLS prevalence ranging between 5% and 10%, and rising to around 10% in the population older than 50 years. This positions RLS next to other common disorders in neurology, like migraine or epilepsy, and documents prevalence rates well above those for common disorders like multiple sclerosis or Parkinson’s disease. Yet, many physicians, including neurologists, seem to be curiously unaware of the disorder or at least seem to fail to establish a diagnosis or initiate treatment in a sizeable proportion of RLS patients. This is despite the fact that RLS was recognized centuries ago by Thomas Willis and aptly and meticulously described and delineated by Karl Axel Ekbom some 60 years ago. Failure to recognize RLS is not an issue of diagnostic difficulty in the strict sense; it can be diagnosed using the basic clinical skills of history taking and a simple set of four essential diagnostic criteria defined and revised by the International Restless Legs Syndrome Study Group (IRLSSG). The failure to recognize RLS is probably just as much an issue of underreporting by patients, who may find their symptoms to be too bizarre to report them to their doctor, as it is one of a lack of appreciation of careful history taking in an age of high-tech and molecular medicine. Some neurologists even claim that, although RLS may be very common, it rarely causes sufficient disability and discomfort to worry about and initiate treatment. Indeed, there has been a paucity of data establishing the severity of RLS in the community. A population-based study, however, has shown that about two thirds of patients with RLS have moderate to marked degrees of severity as measured by the International RLS Severity Scale. This is a strong indication that a majority of RLS sufferers are in need of treatment, but the same population-based study has also shown that very few actually receive it.

This again is in curious contrast to the availability of highly efficient therapies, first and foremost by dopaminergic enhancement with L-dopa or dopamine agonists. This has raised issues about possible links between RLS and Parkinson’s disease as an insufficiently explored area. Whether RLS patients are at greater risk of developing Parkinson’s disease, compared with the general population, remains to be adequately studied. Beyond common dopaminergic responsiveness, however, potential links between these two disorders become less obvious. The mechanism of action of dopaminergic agents in Parkinson’s disease was clearly established decades ago, and there has been increasing refinement of knowledge regarding downstream events following striatal dopamine receptor activation in Parkinson’s disease. However, there remains a striking blank when it comes to understanding where and how L-dopa or dopamine agonists work in RLS. Although there has been some recent evidence to suggest deficient iron transport mechanisms in substantia nigra neurons in RLS, it is unclear if and how this might have any bearing on dopaminergic responsiveness of RLS symptoms. Striatal dopaminergic denervation has never been convincingly demonstrated in RLS. The interaction between iron deficiency and dopaminergic function is another item on the long list of burning questions related to RLS, as is the search for pathogenic mutations in familial cases.

It is time for the entire spectrum of the neurological community to direct their focus on RLS to close the diagnosis−treatment gap in this highly prevalent neurological condition and to solve the many research questions related to its etiology and pathogenesis.