Search for a command to run...
<h3>Introduction</h3> Restless legs syndrome (RLS) is a common debilitating neurological disorder. Midbrain iron deficiency has been implicated in the pathophysiology of RLS. There is evidence that supports the use of ferric carboxymaltose (FCM) in ameliorating RLS severity. This study aims to evaluate the effectiveness of FCM in a cohort with refractory RLS. <h3>Methods</h3> Clinically eligible patients with diagnosed RLS from Guy’s Sleep Disorder Centre, who received single-dose FCM 1000mg as per clinic protocol between January 2020 and January 2023 were included. Electronic patient records were retrospectively reviewed. Ferritin levels and percentage transferrin saturation (TSat%) were recorded at baseline and at 12-weeks post-infusion of FCM. The severity of RLS symptoms as per International RLS Study Group rating scale (IRLS) (range 0–40), was recorded at the same intervals. <h3>Results</h3> Twenty patients (age 51.1±16, 15 female) were identified, with a mean IRLS score of 22.1 ±4.3 and ferritin of 40.9±18.2mcg/L. Ten patients (50%) had a history of anxiety/depression, six (30%) had a history of OSA, and eleven (55%) had unsuccessfully trialled dopamine agonists and gabapentinoids for RLS. At 12-weeks the mean ΔIRLS score was -9.4±1.7 (p=0.001), mean Δferritin was 195.4±96.6mcg/L (p<0.001), and ΔTSat% was 9.8±3.2 (p=0.007).There was a significant negative correlation at 12-weeks between post-infusion ferritin levels and the mean IRLS score (Pearson correlation coefficient= −0.71, p< 0.001). Twelve patients (60%) reported improvement of RLS symptoms at week-12, with five patients (25%) reporting complete resolution of symptoms of which three patients stopped their RLS-medications. Non-responders (table 1) did not report symptom deterioration at week-12 compared to baseline. There were no infusion-related serious adverse events reported; there was one minor side effect reported which self-resolved (fever). <h3>Conclusion</h3> Intravenous FCM conferred significant symptomatic improvement in the majority of patients with severe refractory RLS. The infusion was well tolerated. Further studies are warranted to investigate non-response. <h3>References</h3> Diagnostic and epidemiological overview of Restless legs syndrome. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4:101–19. Pratt DP. Restless legs syndrome/willis-Ekbom disease and periodic limb movements: a comprehensive review of epidemiology, pathophysiology, diagnosis and treatment considerations. Curr Rheumatol Rev 2016;12(2): 91e112. The implication of iron in the pathophysiology of Restless legs syndrome. Allen RP, Barker PB, Wehrl F, et al. MRI measurement of brain iron in patients with restless legs syndrome. Neurology. 2001;56(2):263–5. Connor JR, Boyer PJ, Menzies SL, Dellinger B, Allen RP, Ondo WG, et al. Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome. Neurology 2003;61:304–9. Earley CJ, Barker PB, Horska A, Allen RP. MRI-determined regional brain iron concentrations in early- and late-onset restless legs syndrome. Sleep Med 2006;7:458–61. Earley CJ, Connor JR, Beard JL, Malecki EA, Epstein DK, Allen RP. Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology 2000;54:1698–700. Godau J, Klose U, Di Santo A, Schweitzer K, Berg D. Multiregional brain iron deficiency in restless legs syndrome. Mov Disord 2008;23:1184–7. Mizuno S, Mihara T, Miyaoka T, Inagaki T, Horiguchi J. CSF iron, ferritin and transferrin levels in restless legs syndrome. J Sleep Res 2005;14:43–7. Rizzo G, Manners D, Testa C, et al. Low brain iron content in idiopathic restless legs syndrome patients detected by phase imaging. Mov Disord. 2013;28(13):1886–90. Evidence that supports the use of ferric carboxymaltose in the treatment of Restless legs syndrome. Allen RP, Adler CH, Du W, Butcher A, Bregman DB, Earley CJ. Clinical efficacy and safety of IV ferric carboxymaltose (FCM) treatment of RLS: a multi-centred, placebo-controlled preliminary clinical trial. Sleep Med. 2011; 12: 906–13. Cho YW, Allen RP, Earley CJ. Clinical efficacy of ferric carboxymaltose treatment in patients with restless legs syndrome. Sleep Med . 2016; 25: 16–23. Hornyak M, Scholz H, KiemenA, Kassubek J. Investigating the responses to intravenous iron in restless legs syndrome: an observational study. Sleep Med . 2012; 13: 732–5. Trenkwalder C, Winkelmann J, Oertel W, Virgin G, Roubert B, Mezzacasa A; FCM-RLS Study Investigators. Ferric carboxymaltose in patients with restless legs syndrome and nonanemic iron deficiency: A randomized trial. Mov Disord. 2017 Oct;32(10):1478–1482.