Objective: Associations between peripheral neuropathy and restless legs syndrome (RLS) have been described, but have not been consistently reproduced. If RLS prevalence is truly increased by neuropathy, this has important implications for RLS pathophysiology.

Methods: In a case-control design, 245 patients with peripheral neuropathy and 245 age- and sex-matched controls were screened for RLS using a standardized phone questionnaire based on international RLS diagnostic criteria. All persons who answered yes to three of four criteria were considered screen-positive. All screen-positive patients underwent a confirmatory diagnostic evaluation by a movement disorders specialist blinded to the neuropathy status of the patient. RLS prevalence was calculated and compared using Fisher exact test.

Results: A total of 65 (26.5%) patients with neuropathy screened positive compared to 25 (10.2%) controls (p < 0.0001). However, the diagnosis was confirmed in only 46% of screen-positive patients with neuropathy, vs 80% of controls (p = 0.005). Cramps and paresthesia without true diurnal variation or rest exacerbation were the commonest causes of false-positive screens. After diagnostic confirmation, the overall prevalence of RLS did not differ between neuropathy patients and controls (12.2% vs 8.2%, p = 0.14). However, when classified by etiology, RLS was found in 14/72 (19.4%) patients with hereditary neuropathy, a prevalence higher than found in controls (p = 0.016) and acquired neuropathy (9.2%, p = 0.033). Among patients with neuropathy, those with RLS more commonly had a family history of RLS (37% vs 15%, p = 0.007) and were younger (49.9 vs 61.4, p = 0.0003).

Conclusions: Restless legs syndrome is more prevalent among patients with hereditary neuropathy, but not in those with acquired neuropathies.