The complexities in the differential diagnosis of restless legs syndrome (Willis-Ekbom disease)

We present a literature review on the clinical conundrums surrounding the differential diagnosis of restless legs syndrome (RLS, Willis-Ekbom disease), as well as conditions that can mimic RLS. An extensive literature search showed that secondary causes of RLS ranged from commonly recognized causes, such as iron deficiency anemia, to less widely noted causes, such as rheumatoid disorders and hypothyroidism. There is a controversial association with Parkinson's disease, essential tremor, and RLS, whereby RLS is proposed as a prodromal feature.

The clinical presentation of restless legs syndrome (RLS), a highly prevalent movement disorder usually during sleep with a circadian variation. The review highlights differences between commonly established secondary causes of RLS, RLS mimics, genetic and drug-induced RLS. A flowchart presents some key features of different and overlapping secondary RLS and mimics and genetic RLS.

RLS is one of the commonest movement disorders and the International Restless Legs Syndrome Study Group has suggested five-point criteria for robust diagnosis of RLS. However, even in expert hands, diagnosis is accurate in about 85% and misdiagnosis, especially with 'RLS mimics,' appears to be high. There are wide variations in the way RLS can present, and this includes different types of secondary RLS as well as drug induced or genetic patterns of RLS. Secondary RLS is highly complex and can be associated with Parkinson's disease as well as prodromal stage of Parkinson and essential tremor. Other known causes of secondary RLS are many and include end-stage kidney disease as well as metabolic disorders to painful conditions such as rheumatic disorders and fibromyalgia and polyradiculopathy.