Ferritin levels in the cerebrospinal fluid and restless legs syndrome: Effects of different clinical phenotypes

Study Objective: To determine whether patients with restless legs syndrome (RLS) and controls differ in regard to levels of ferritin and transferrin in the cerebrospinal fluid (CSF) when samples are collected at night, to determine whether patients with early-onset and late-onset RLS show a different outcome for CSF values, and to determine whether the CSF ferritin level correlates with disease severity. Design: Collection of CSF and plasma; assessment of disease severity using objective (periodic limb movements) and subjective (Johns Hopkins Restless Legs Severity Scale) measures of severity. Setting: General Clinical Research Center. Participants: Thirty subjects with idiopathic RLS (15 early- and 15 late-onset RLS) and 22 age- and sex-matched controls. Intervention: N/A. Results: Nighttime CSF ferritin levels were lower in the total RLS group compared with controls. Further assessment found that the early-onset (less than 45 years of age) but not the late-onset (greater than or equal to 45 years of age) RLS group had significantly lower CSF ferritin levels compared with controls. There was a strong correlation between the age of symptom onset and CSF ferritin values (r = 0.64): the earlier the age, the lower the ferritin level. A regression analysis showed that both sex and RLS subtype had significant effects on the CSF ferritin level, with women with early-onset RLS having substantial lower values than men with late-onset RLS. A comparison between these nighttime CSF values and previously published daytime samples suggests that diurnal changes may have effects on the findings. Conclusions: This study is distinct in showing that the degree of the CSF-ferritin effect is best defined by the clinical phenotypes of sex and age of symptom onset and by the time of day that samples are collected.