CSF iron, ferritin and transferrin levels in restless legs syndrome

Abstract

Summary The aim of this study is evaluating iron, ferritin, and transferrin in both serum and CSF in patients of restless legs syndrome (RLS), based on the hypothesis that iron deficiency in the central nervous system (CNS) causes the symptoms as a result of the dysfunction of dopaminergic systems. These parameters, polysomnographic sleep measures, and subjective evaluation of the sleep quality were compared in 10 patients of idiopathic RLS (RLS group) and 10 age‐matched patients of psychophysiological insomnia without RLS symptoms (non‐RLS group). With sleep patterns, sleep latency was longer and sleep efficiency was lower in the RLS group than those in the non‐RLS group. Periodic leg movement index in the RLS group was higher than that of the non‐RLS group. With serum examination, there were no significant differences for the iron, ferritin, and transferrin values between the both groups. With CSF examination, the iron and ferritin values were lower and the transferrin values were higher in the RLS group than those in the non‐RLS group. There was positive correlation between the serum and CSF ferritin levels in the both groups, but the slope of the regression lines for the RLS group was lower than that for the non‐RLS group. These results indicate low brain iron concentration caused by the dysfunction of iron transportation from serum to CNS in patients with idiopathic RLS.

Association between Low Serum Ferritin and Restless Legs Syndrome in Patients with Attention Deficit Hyperactivity Disorder

“…It has been suggested that iron is closely related to dopamine metabolism being a coenzyme of tyrosine hydroxylase, and that D2 and D4 receptor and dopamine transporter densities decrease with decreased brain iron levels (Ashkenazi et al 1982;Ericson et al 1997). In patients with RLS, reduced brain iron concentration may be due to dysfunctional iron transportation (Mizuno et al 2005). It can be speculated that iron defi ciency may cause further alterations in brain dopaminergic system, which seems to be already impaired in ADHD subjects (Volkow et al 2007), and lead to a higher rate of RLS, which is associated with alterations of both the iron metabolism and the dopaminergic system (Winkelman 2006).…”

“…Thus, it has been recommended that serum ferritin level must be evaluated in every RLS subject (Trenkwalder et al 2005). It has been reported that decreased brain iron concentration might be due to dysfunctional transportation of iron from serum to the cerebrospinal fl uid (Mizuno et al 2005). It has been shown that the transport of iron into dopaminergic cells might be decreased in RLS (Connor et al 2003).…”

“…Other studies have focused on the utility of iron supplementation in ADHD, with confl icting results (Sever et al 1997). Serum ferritin level is related to RLS severity (Krieger and Schroeder 2001), and since most of the subjects with iron defi ciency do not have anemia, low serum or cerebro-spinal fl uid ferritin levels may be the only signifi cant parameter (Sun et al 1998;Kryger et al 2002;Mizuno et al 2005). Thus, it has been recommended that serum ferritin level must be evaluated in every RLS subject (Trenkwalder et al 2005).…”

A randomized, double-blind, placebo-controlled trial of intravenous iron sucrose in restless legs syndrome

“…In the last 10 years there have been several studies which have examined this hypothesis in regards to brain iron. CSF analyses of ferritin, MRI quantification and B-mode imaging of iron in the brain, and finally autopsy studies have all implicate brain iron insufficiency as a primary player in the underlying pathology of RLS [2][3][4][5][6][7]. The CSF, MRI and B-mode imaging studies demonstrated brain iron changes despite measures of plasma iron status being in the normal clinical range.…”

Plasma iron levels appraised 15 days after spinal cord injury in a limb movement animal model

“…The SCI7 showed significantly lower plasma iron (F (2,14) ¼ 11.540, P ¼ 0.00109; ANOVA) and transferrin (F (2,14) ¼ 12.364, P ¼ 0.00081; ANOVA) levels relative to the CTRL7 and SHAM7 groups (Figure 2a).…”