Restless legs syndrome in Friedreich ataxia: a polysomnographic study

Friedreich ataxia (FA) is the most common type of hereditary ataxia. Frataxin deficiency due to a GAA expansion in the first intron of chromosome 9 results in intramitochondrial iron accumulation. On the basis of the patients' complaints about sleep disturbance and pathophysiological considerations, we systematically assessed sleep history and polysomnography in FA. We included 16 consecutive FA patients (11 men, 5 women; mean age, 35.4 ± 11.1 years) with a mean disease duration of 16.5 ± 7.0 years. All patients underwent a standardized protocol including a detailed sleep history and polysomnographic recordings. Eight out of 16 patients were diagnosed with restless legs syndrome (RLS). In seven patients, RLS onset was after the onset of FA. Interestingly, FA patients with RLS had significantly lower serum ferritin levels than FA patients without RLS (76.3 ± 56.0 μg/L vs. 176.3 ± 100.7 μg/L; P = 0.043 after correction for sex and age). Moreover, periodic leg movements in wakefulness (PLMW) indices were significantly higher in FA patients with RLS than FA patients without RLS (FA with RLS, 118.1 ± 50.7; FA without RLS, 65.6 ± 44.2; P = 0.028). There was an inverse correlation between serum ferritin levels and PLMW indices obtained in all FA patients (rho -0.538, P = 0.039). RLS is common in FA. Its frequency in this primarily spinal ataxia appears consistent with the concept of dysfunctional spinal sensorimotor integration in the pathophysiology of RLS. The finding that RLS is more frequent in the context of lower serum ferritin levels in FA is interesting, but requires further investigation in larger patient samples.