The restless legs syndrome.
Progress in Neurobiology. 2005-10-01; 77(3): 139-165
DOI: 10.1016/j.pneurobio.2005.10.007
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The restless legs syndrome (RLS) is one of the commonest neurological
sensorimotor disorders at least in the Western countries and is often associated
with periodic limb movements (PLM) during sleep leading to severe insomnia.
However, it remains largely underdiagnosed and its underlying pathogenesis is
presently unknown. Women are more affected than men and early-onset disease is
associated with familial cases. A genetic origin has been suggested but the mode
of inheritance is unknown. Secondary causes of RLS may share a common underlying
pathophysiology implicating iron deficiency or misuse. The excellent response to
dopaminegic drugs points to a central role of dopamine in the pathophysiology of
RLS. Iron may also represent a primary factor in the development of RLS, as
suggested by recent pathological and brain imaging studies. However, the way
dopamine and iron, and probably other compounds, interact to generate the
circadian pattern in the occurrence of RLS and PLM symptoms remains unknown. The
same is also the case for the level of interaction of the two compounds within
the central nervous system (CNS). Recent electrophysiological and animals studies
suggest that complex spinal mechanisms are involved in the generation of RLS and
PLM symptomatology. Dopamine modulation of spinal reflexes through dopamine D3
receptors was recently highlighted in animal models. The present review suggests
that RLS is a complex disorder that may result from a complex dysfunction of
interacting neuronal networks at one or several levels of the CNS and involving
numerous neurotransmitter systems.