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Ferritin deficiency may contribute to restless legs syndrome symptom severity
ARTICLE IN PRESS Sleep Medicine ■■ (2015) ■■
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Sleep Medicine j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / s l e e p
Letter to the Editor Ferritin deficiency may contribute to restless legs syndrome symptom severity To the Editor: We have read Winkelman et al.’s study with great interest [1]. In this study, they aimed to quantify gamma-aminobutyric acid (GABA), glutamate, and N-acetyl aspartate (NAA) levels in the anterior cingulate cortex (ACC), thalamus, and cerebellum in patients with restless legs syndrome (RLS) and matched controls [1]. They reported that there were no differences in GABA or glutamate levels between patients with RLS and matched healthy controls in the cerebellum, thalamus, or ACC using 1H-MRS at 4 T. They also reported that in exploratory analyses they did demonstrate relationships between GABA levels and both RLS severity and actigraphyderived PLM indices in patients with RLS, with positive correlations observed in the thalamus and negative correlations in the cerebellum [1]. When we inspected the study model [1], we find that all subjects were evaluated with an unstructured clinical interview for history of sleep, psychiatric, and medical disorders. Base-line laboratories included urine toxicology and pregnancy testing (for female subjects). The authors have established a wide range of exclusion criteria. Unfortunately they failed to consider serum ferritin levels. There are some conditional evidences for a role of the dopaminergic system and iron status in the pathophysiology of RLS [2]. Tyrosine hydroxylase is an enzyme in the production of dopamine. This enzyme needs iron as a cofactor for hydroxylation of tyrosine [3]. The most of the iron in the brain is located in ferritin. Low serum ferritin status is an important contributor to the development of RLS with/without anemia [4]. It is reported that the patients with the level of ferritin below 50 ng per mL had severe symptoms of the RLS [5].
In the light of previous reports, a few questions arise about the results of Winkelman et al.’s study [1]. A possible ferritin deficiency might be a confounding factor for their finding regarding glutamate GABA and NAA in certain brain areas. Did the authors evaluate ferritin deficiency in the study group for the severity of RLS? If yes, this issue should be declared by the authors. If not, readers should keep in mind that ferritin deficiency might have an effect on the severity of RLS. References [1] Winkelman JW, Schoerning L, Platt S, et al. Restless legs syndrome and central nervous system gammaaminobutyric acid: preliminary associations with periodic limb movements in sleep and restless leg syndrome symptom severity. Sleep Med 2014;15:1225–30. [2] Allen RP, Earley CJ. Restless legs syndrome. A review of clinical and pathophysiologic features. J Clin Neurophysiol 2001;18:128–47. [3] Cooper JR, Bloom FE, Roth RH. The biochemical basis of neuropharmacology. New York: Oxford University Press; 1991. [4] O’Keeffe S, Gavin K, Lavan J. Iron status and restless legs syndrome in the elderly. Age Ageing 1994;23:200–3. [5] Sun ER, Chen CA, Ho G, et al. Iron and the restless legs syndrome. Sleep 1998;21:371–7.
Serdar Tasdemir * Department of Neurology, Beytepe Military Hospital, Ankara, Turkey * Address: Department of Neurology, Beytepe Military Hospital, Cankaya, Ankara, Turkey. Tel.: +90 533 8192791; fax: +90 312 3044475. E-mail address: [email protected] Oguzhan Oz Department of Neurology, Gulhane Military Medical Academy, Ankara, Turkey Available online
http://dx.doi.org/10.1016/j.sleep.2015.09.013 1389-9457/© 2015 Published by Elsevier B.V.
Please cite this article in press as: Serdar Tasdemir, Oguzhan Oz, Ferritin deficiency may contribute to restless legs syndrome symptom severity, Sleep Medicine (2015), doi: 10.1016/ j.sleep.2015.09.013
Contents lists available at ScienceDirect
Sleep Medicine j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / s l e e p
Letter to the Editor Ferritin deficiency may contribute to restless legs syndrome symptom severity To the Editor: We have read Winkelman et al.’s study with great interest [1]. In this study, they aimed to quantify gamma-aminobutyric acid (GABA), glutamate, and N-acetyl aspartate (NAA) levels in the anterior cingulate cortex (ACC), thalamus, and cerebellum in patients with restless legs syndrome (RLS) and matched controls [1]. They reported that there were no differences in GABA or glutamate levels between patients with RLS and matched healthy controls in the cerebellum, thalamus, or ACC using 1H-MRS at 4 T. They also reported that in exploratory analyses they did demonstrate relationships between GABA levels and both RLS severity and actigraphyderived PLM indices in patients with RLS, with positive correlations observed in the thalamus and negative correlations in the cerebellum [1]. When we inspected the study model [1], we find that all subjects were evaluated with an unstructured clinical interview for history of sleep, psychiatric, and medical disorders. Base-line laboratories included urine toxicology and pregnancy testing (for female subjects). The authors have established a wide range of exclusion criteria. Unfortunately they failed to consider serum ferritin levels. There are some conditional evidences for a role of the dopaminergic system and iron status in the pathophysiology of RLS [2]. Tyrosine hydroxylase is an enzyme in the production of dopamine. This enzyme needs iron as a cofactor for hydroxylation of tyrosine [3]. The most of the iron in the brain is located in ferritin. Low serum ferritin status is an important contributor to the development of RLS with/without anemia [4]. It is reported that the patients with the level of ferritin below 50 ng per mL had severe symptoms of the RLS [5].
In the light of previous reports, a few questions arise about the results of Winkelman et al.’s study [1]. A possible ferritin deficiency might be a confounding factor for their finding regarding glutamate GABA and NAA in certain brain areas. Did the authors evaluate ferritin deficiency in the study group for the severity of RLS? If yes, this issue should be declared by the authors. If not, readers should keep in mind that ferritin deficiency might have an effect on the severity of RLS. References [1] Winkelman JW, Schoerning L, Platt S, et al. Restless legs syndrome and central nervous system gammaaminobutyric acid: preliminary associations with periodic limb movements in sleep and restless leg syndrome symptom severity. Sleep Med 2014;15:1225–30. [2] Allen RP, Earley CJ. Restless legs syndrome. A review of clinical and pathophysiologic features. J Clin Neurophysiol 2001;18:128–47. [3] Cooper JR, Bloom FE, Roth RH. The biochemical basis of neuropharmacology. New York: Oxford University Press; 1991. [4] O’Keeffe S, Gavin K, Lavan J. Iron status and restless legs syndrome in the elderly. Age Ageing 1994;23:200–3. [5] Sun ER, Chen CA, Ho G, et al. Iron and the restless legs syndrome. Sleep 1998;21:371–7.
Serdar Tasdemir * Department of Neurology, Beytepe Military Hospital, Ankara, Turkey * Address: Department of Neurology, Beytepe Military Hospital, Cankaya, Ankara, Turkey. Tel.: +90 533 8192791; fax: +90 312 3044475. E-mail address: [email protected] Oguzhan Oz Department of Neurology, Gulhane Military Medical Academy, Ankara, Turkey Available online
http://dx.doi.org/10.1016/j.sleep.2015.09.013 1389-9457/© 2015 Published by Elsevier B.V.
Please cite this article in press as: Serdar Tasdemir, Oguzhan Oz, Ferritin deficiency may contribute to restless legs syndrome symptom severity, Sleep Medicine (2015), doi: 10.1016/ j.sleep.2015.09.013