What Causes the Syndrome?
RLS was originally believed to be related to an accumulation of metabolites caused by venous congestion in the legs. Peripheral neuropathies have also been postulated, but no structural neural changes have ever been demonstrated. Most authors today agree that RLS has its origins in the subcortical CNS, with involvement of the brainstem and spinal cord. On the basis of responses to treatment with dopaminergic drugs, the involvement of dopaminergic receptors has been suggested. The endogenous opioid system may also be involved through an influence on a primary dopaminergic mechanism.
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Cite this: Drug Treatment Available for Patients With Severe Restless Legs Syndrome - Medscape - Jun 19, 2000.