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Abstract

A restless investigatorIn the last 10 years, it has been noticed that patients with the “restless legs syndrome” became much more symptomatic if they were iron deficient. It was also noticed that patients with the syndrome, on average, had lower iron stores than did asymptomatic people. Eventually, people began giving iron supplements to patients with restless legs, even if they did not have anemia or iron stores that were clearly outside the normal range; sometimes, this led to a fairly striking clinical improvement. At the same time, evidence has been accumulating that dopaminergic function is abnormal in patients with the syndrome, and antiparkinsonian drugs have enjoyed some success.The concept that restless legs syndrome involves abnormalities in the iron status of the CNS has gained credibility with a number of recent studies, one of which is presented within the pages of this month’s issue (see page 67): Dr. Stacey Clardy and colleagues found decreased amounts of ferritin subunits in the spinal fluid from restless-legs patients when compared to spinal fluid from people who did not have the syndrome.The fact that some people have uncommon unpleasant sensations in their legs, leading to an almost akathitic need to keep them moving (and seriously disrupting sleep) is anything but a new observation. In 1672, Thomas Willis (famous as the discoverer of the arterial anastamoses at the base of the brain) described patients whose attempts at sleep were accompanied by “(l)eaping and contractions of the tendons and so great a restlessness and tossing of the members … that the diseased are no more able to sleep, than if they were in the place of the greatest torture!” The modern description of the malady, and the term, “restless legs syndrome,” date from a 1944 paper by Prof. Karl-Axel Ekbom of the University of Uppsala.This month’s cover illustration is a reproduction of the frontispiece from Willis’ book, The London Practice of Physick. We thank the staff of the Owen H. Wangensteen Historical Library of Biology and Medicine for access to this rare book. A restless investigatorIn the last 10 years, it has been noticed that patients with the “restless legs syndrome” became much more symptomatic if they were iron deficient. It was also noticed that patients with the syndrome, on average, had lower iron stores than did asymptomatic people. Eventually, people began giving iron supplements to patients with restless legs, even if they did not have anemia or iron stores that were clearly outside the normal range; sometimes, this led to a fairly striking clinical improvement. At the same time, evidence has been accumulating that dopaminergic function is abnormal in patients with the syndrome, and antiparkinsonian drugs have enjoyed some success.The concept that restless legs syndrome involves abnormalities in the iron status of the CNS has gained credibility with a number of recent studies, one of which is presented within the pages of this month’s issue (see page 67): Dr. Stacey Clardy and colleagues found decreased amounts of ferritin subunits in the spinal fluid from restless-legs patients when compared to spinal fluid from people who did not have the syndrome.The fact that some people have uncommon unpleasant sensations in their legs, leading to an almost akathitic need to keep them moving (and seriously disrupting sleep) is anything but a new observation. In 1672, Thomas Willis (famous as the discoverer of the arterial anastamoses at the base of the brain) described patients whose attempts at sleep were accompanied by “(l)eaping and contractions of the tendons and so great a restlessness and tossing of the members … that the diseased are no more able to sleep, than if they were in the place of the greatest torture!” The modern description of the malady, and the term, “restless legs syndrome,” date from a 1944 paper by Prof. Karl-Axel Ekbom of the University of Uppsala.This month’s cover illustration is a reproduction of the frontispiece from Willis’ book, The London Practice of Physick. We thank the staff of the Owen H. Wangensteen Historical Library of Biology and Medicine for access to this rare book. In the last 10 years, it has been noticed that patients with the “restless legs syndrome” became much more symptomatic if they were iron deficient. It was also noticed that patients with the syndrome, on average, had lower iron stores than did asymptomatic people. Eventually, people began giving iron supplements to patients with restless legs, even if they did not have anemia or iron stores that were clearly outside the normal range; sometimes, this led to a fairly striking clinical improvement. At the same time, evidence has been accumulating that dopaminergic function is abnormal in patients with the syndrome, and antiparkinsonian drugs have enjoyed some success. The concept that restless legs syndrome involves abnormalities in the iron status of the CNS has gained credibility with a number of recent studies, one of which is presented within the pages of this month’s issue (see page 67): Dr. Stacey Clardy and colleagues found decreased amounts of ferritin subunits in the spinal fluid from restless-legs patients when compared to spinal fluid from people who did not have the syndrome. The fact that some people have uncommon unpleasant sensations in their legs, leading to an almost akathitic need to keep them moving (and seriously disrupting sleep) is anything but a new observation. In 1672, Thomas Willis (famous as the discoverer of the arterial anastamoses at the base of the brain) described patients whose attempts at sleep were accompanied by “(l)eaping and contractions of the tendons and so great a restlessness and tossing of the members … that the diseased are no more able to sleep, than if they were in the place of the greatest torture!” The modern description of the malady, and the term, “restless legs syndrome,” date from a 1944 paper by Prof. Karl-Axel Ekbom of the University of Uppsala. This month’s cover illustration is a reproduction of the frontispiece from Willis’ book, The London Practice of Physick. We thank the staff of the Owen H. Wangensteen Historical Library of Biology and Medicine for access to this rare book. Ferritin subunits in CSF are decreased in restless legs syndromeThe Journal of Laboratory and Clinical MedicineVol. 147Issue 2PreviewRestless legs syndrome (RLS) is a neurological disorder that may be related to iron misregulation at the level of the central nervous system. Evidence that iron is involved in RLS comes from magnetic resonance imaging data, autopsy studies, analyses of cerebrospinal fluid (CSF), and correlations of symptoms with serum ferritin. To further examine the possibility that brain iron status is insufficient in RLS, we determined ferritin levels in the CSF. Specifically, we differentiated between the H- and L-subunits of ferritin, because these peptides are expressed from different chromosomes and have different functions. Full-Text PDF