**9. References**


RLS is a common medical disorder which remains underdiagnosed. The underlying etiology is still not fully elucidated but there is increasing understanding of some mechanisms of disease especially in secondary RLS. Many treatment options are available although issues of augmentation and rebound continue to cause problems with RLS control. It is highly recommended that health care providers be aware of RLS symptoms and recognize the

Agarwal P, Griffith A. (2008) Restless legs syndrome: a unique case and essentials of

Allen RP, Earley CJ. (1996) Augmentation of the restless legs syndrome with

Allen RP, Earley CJ. (2000) Defining the phenotype of the restless legs syndrome (RLS)

Allen RP, Picchietti D, Hening W, Trenkwalder C, Walters A, Montplaisi J. (2003) Restless

Allen RP, Ritchie SY. (2008) Clinical efficacy of ropinirole for restless legs syndrome is not

Auger C, Montplaisir J, Duquette P. (2005) Increased frequency of restless legs syndrome in a French-Canadian population with multiple sclerosis. *Neurology* 2005;65:1652-53. Arunthari V, Kaplan J, Fredrickson PA, Lin SC, Castillo PR, Heckman MG. (2010)

Bachmann CG, Rolke R, Scheidt U, Stadelmann C, Sommer M, Pavlakovic G, Happe S,

Balendran J, Champion D, Jaaniste T, Welsh A. (2011). A common sleep disorder in

Benes H, Mattern W, Peglau I, Dreykluft T, Bergmann L, Hansen C, Kohnen R, Banik N,

Benediktsdottir B, Janson C, Lindberg E, Arnardóttir E, Olafsson I, Cook E, Thorarinsdottir

Berger K, Luedemann J, Trenkwalder C, John U, Kessler C. (2004) Sex and the risk of restless

the National Institutes of Health. *Sleep Med*. 2003 Mar;4(2):101-19.

affected by age at symptom onset. *Sleep Med*. 2008 Dec;9(8):899-902.

legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at

Prevalence of Restless Legs Syndrome in Blood Donors. *Mov Disord*. 2010 Jul

Treede RD, Paulus W. (2010) Thermal hypoesthesia differentiates secondary restless legs syndrome associated with small fiber neuropathy from primary

pregnancy: Restless legs syndrome and its predictors. *Aust N Z J Obstet Gynaecol*.

Schoen SW, Hornyak M. (2011) Ropinirole improves depressive symptoms and restless legs syndrome severity in RLS patients: a multicentre, randomized,

EH, Gislason T. (2010) Prevalence of restless legs syndrome among adults in Iceland and Sweden: Lung function, comorbidity, ferritin, biomarkers and quality

legs syndrome in the general population. *Arch Intern Med*. 2004 Jan 26;164(2):196-202.

diagnosis and treatment. *Medscape J Med*. 2008;10(12):296.

carbidopa/levodopa. *Sleep*. 1996 Apr;19(3):205-13.

using age-of-symptom-onset. *Sleep Med* 2000; 1: 11–9.

restless legs syndrome. *Brain*. 2010 Mar;133(Pt 3):762-70.

placebo- controlled study. *J Neurol*. 2011 Jun;258(6):1046-54.

of life. *Sleep Med*. 2010 Dec;11(10):1043-8.

**8. Conclusion** 

**9. References** 

disease in their patients.

30;25(10):1451-5.

2011 Jun;51


Risk Factors and Treatment of Restless Legs Syndrome in Adults 177

Kanter AH. (1995) The effect of sclerotherapy on restless legs syndrome. *Dermatol Surg*. 1995

Kilfoyle DH, Dyck PJ, Wu Y, Litchy WJ, Klein DM, Dyck PJ, Kumar N, Cunningham JM,

Kushida C, Martin M, Nikam P, Blaisdell B, Wallenstein G, Ferini-Strambi L, Ware JE Jr.

LaRochelle JS, Karp BI. (2004) Restless legs syndrome due to interferon- alpha. *Mov Disord*.

Lettau LA, Gudas CJ, Kaelin TD. (2010) Remission of restless legs syndrome and periodic

Lettieri CJ, Eliasson AH. (2009) Pneumatic compression devices are an effective therapy for

Lin SC, Kaplan J, Burger CD, Fredrickson PA. (1998) Effect of pramipexole in treatment of resistant restless legs syndrome. *Mayo Clin Proc*. 1998 Jun;73(6):497-500. Lo Coco D, Cannizzaro E, Lopez G. (2009) Restless legs syndrome in a patient with

Manconi M, Govoni V, De Vito A, Economou NT, Cesnik E, Casetta I, Mollica G, Ferini-

Manconi M, Fabbrini M, Bonanni E, Filippi M, Rocca M, Murri L, Ferini- Strambi L. (2007)

Manconi M, Rocca MA, Ferini-Strambi L, Tortorella P, Agosta F, Comi G, Filippi M. (2008)

Manconi M, Ferri R, Zucconi M, Oldani A, Giarolli L, Bottasini V, Ferini- Strambi L. (2011).

Manconi M, Ferri R, Zucconi M, Clemens S, Giarolli L, Bottasini V, Ferini- Strambi L. (2011)

Marin LF, dos Santos WA, Pedroso JL, Ferraz HB, de Carvalho LB, do Prado GF. (2010)

Merlino G, Lorenzut S, Gigli GL, Romano G, Montanaro D, Moro A, Valente M. (2010) A

Michaud M, Soucy JP, Chabli A, Lavigne G, Montplaisir J. (2002) SPECT imaging of striatal

multifocal motor neuropathy. *Neurol Sci*. 2009 Oct;30(5):401-3.

with cervical cord damage. *Mult Scler*. 2008 Jan;14(1):86-93.

syndrome. *Mov Disord.* 2011 Apr;26(5):892-5.

cases. *Parkinsonism Relat Disord*. 2010 Jul;16(6):418-9.

renal failure. *Mov Disord*. 2010 Jun 15;25(8):1019-25.

leg movements in sleep. *J Neurol.* 2002;249:164–70.

*Neurology*. 2011 12;77(2):110-7.

sclerosis*. J Neurol Neurosurg Psychiatry*. 2006 Aug;77(8):963-6.

report. *J Med Case Reports*. 2010 Sep 17;4:306.

controlled trial. *Chest*. 2009 Jan;135(1):74-80.

Klein CJ. (2006) Myelin protein zero mutation His39Pro: hereditary motor and sensory neuropathy with variable onset, hearing loss, restless legs and multiple

(2007) Burden of restless legs syndrome on health-related quality of life. *Qual Life* 

limb movements in sleep after bilateral excision of multiple foot neuromas: a case

restless legs syndrome: a prospective, randomized, double-blinded, sham-

Strambi L, Granieri E. (2004) Restless legs syndrome and pregnancy. *Neurology*.

High prevalence of restless legs syndrome in multiple sclerosis. *Eur J Neurol*. 2007

Restless legs syndrome is a common finding in multiple sclerosis and correlates

Pramipexole versus ropinirole: polysomnographic acute effects in restless legs

Preferential D2 or preferential D3 dopamine agonists in restless legs syndrome.

Restless legs syndrome associated with Guillain- Barré syndrome: a report of two

case-control study on restless legs syndrome in nondialyzed patients with chronic

pre- and postsynaptic dopaminergic status in restless legs syndrome with periodic

Apr;21(4):328-32.

*Res*. 2007;16:617-624.

2004 Jun;19(6):730-1.

2004 Sep 28;63(6):1065-9.

May;14(5):534-9.

Ekbom K. (1945) Restless legs: a clinical study. *Acta Med Scand Suppl* 1945;158:1–123.


Facco FL, Kramer J, Ho KH, Zee PC, Grobman WA. (2010) Sleep disturbances in pregnancy.

Gao X, Schwarzschild MA, O'Reilly EJ, Wang H, Ascherio A. (2010) Restless legs syndrome and Parkinson's Disease in men. *Mov Disord*. 2010 Nov 15;25(15):2654-7. Gemignani F, Marbini A, Di Giovanni G, Salih S, Margarito FP, Pavesi G, Terzano

Gemignani F, Brindani F, Vitetta F, Marbini A, Calzetti S. (2007) Restless legs syndrome in

Ghorayeb I, Bioulac B, Scribans C, Tison F. (2008) Perceived severity of restless legs syndrome across the female life cycle. *Sleep Med*. 2008 Oct;9(7):799-802. Goffredo Filho GS, Gorini CC, Purysko AS, Silva HC, Elias IE. (2003) Restless legs

Hansen RA, Song L, Moore CG, Gilsenan AW, Kim MM, Calloway MO, Murray MD. (2009)

Hassan N, Pineau CA, Clarke AE, Vinet E, Ng R, Bernatsky S. (2011) Systemic lupus and

Hattan E, Chalk C, Postuma RB. (2009) Is there a higher risk of restless legs syndrome in

Hayes CA, Kingsley JR, Hamby KR, Carlow J. (2008) The effect of endovenous laser

Hening WA, Walters A, Kavey N, Gidro-Frank S, Côté L, Fahn S. (1986) Dyskinesias while

Hening WA, Allen RP, Ondo WG, Walters AS, Winkelman JW, Becker P, Bogan R, Fry JM,

Högl B, Garcia-Borreguero D, Trenkwalder C, Ferini-Strambi L, Hening W, Poewe W,

Inoue Y, Kuroda K, Hirata K, Uchimura N, Kagimura T, Shimizu T. (2010) Long-term open-

Italian REMS Study Group, Manconi M, Ferini-Strambi L, Filippi M, Bonanni E, Iudice A,

Kaplan PW, Allen RP, Buchholz DW, Walters JK. (1993) A double-blind, placebo-controlled

carbidopa/levodopa and propoxyphene. *Sleep*. 1993 Dec;16(8):717-23.

multiple sclerosis: the REMS study. *Sleep*. 2008 Jul;31(7):944-52.

awake and periodic movements in sleep in restless legs syndrome: treatment with

Kudrow DB, Lesh KW, Fichtner A, Schollmayer E; SP792 Study Group. (2010) Rotigotine improves restless legs syndrome: a 6-month randomized, double-blind, placebo- controlled trial in the United States. *Mov Disord.* 2010 Aug 15;25(11):1675-83.

Brenner SS, Fraessdorf M, Busse M, Albrecht S, Allen RP. (2011) Efficacy and augmentation during 6 months of double- blind pramipexole for restless legs

label study of pramipexole in patients with primary restless legs syndrome. *J* 

Murri L. (2008) Multicenter case-control study on restless legs syndrome in

study of the treatment of periodic limb movements in sleep using

risk of restless legs syndrome*. J Rheumatol* 2011; 38(5):874-6.

peripheral neuropathy? *Neurology* 2009 Mar 17;72(11):955-60.

ablation on restless legs syndrome. *Phlebology* 2008;23:112–117.

MG.(1997) Cryoglobulinaemic neuropathy manifesting with restless legs

diabetic neuropathy: a frequent manifestation of small fiber neuropathy. *J Peripher* 

syndrome in patients on chronic hemodialysis in a Brazilian city: frequency, biochemical findings and co-morbidities. *Arq Neuropsiquiatr*. 2003 Sep;61(3B):723-7.

Effect of ropinirole on sleep outcomes in patients with restless legs syndrome: meta-analysis of pooled individual patient data from randomized controlled trials.

Ekbom K. (1945) Restless legs: a clinical study. *Acta Med Scand Suppl* 1945;158:1–123.

*Obstet Gynecol*. 2010;115(1):77-83.

*Nerv Syst*. 2007 Mar;12(1):50-3.

*Pharmacotherapy*. 2009 Mar;29(3):255-62.

opioids. *Neurology*. 1986 Oct;36(10):1363-6.

syndrome. *Sleep Med*. 2011 Apr;12(4):351-60.

*Neurol Sci*. 2010 Jul 15;294(1- 2):62-6.

syndrome. *J Neurol Sci*. 1997 Nov 25;152(2):218- 23.


Risk Factors and Treatment of Restless Legs Syndrome in Adults 179

Partinen M, Hirvonen K, Jama L, Alakuijala A, Hublin C, Tamminen I, Koester J, Reess J.

Paulus W, Trenkwalder C. (2006) Less is more: pathophysiology of dopaminergic-therapy-

Quiroz C, Pearson V, Gulyani S, Allen R, Earley C, Ferré S. (2010) Up-regulation of striatal

Rijsman RM, de Weerd AW, Stam CJ, Kerkhof GA, Rosman JB. (2004) Periodic limb

Russell, M. (2007) Massage therapy and restless legs syndrome. *J Bodywork Movement Ther*

Salih AM, Gray RES, Mills KR, Webley M. (1994) A clinical, serological and

Sikandar R, Khealani BA, Wasay M. (2009) Predictors of restless legs syndrome in

Snyder AM, Wang X, Patton SM, Arosio P, Levi S, Earley CJ, Allen RP, Connor JR. (2009)

Sperfeld AD, Unrath A, Kassubek J. (2007) Restless legs syndrome in hereditary spastic

Stiasny K, Röbbecke J, Schüler P, Oertel WH. (2000) Treatment of idiopathic restless legs

Stiasny-Kolster K, Kohnen R, Schollmayer E, Möller JC, Oertel WH; Rotigotine Sp 666 Study

Synofzik M, Godau J, Lindig T, Schöls L, Berg D. (2011) Restless legs and substantia nigra

Takaki J, Nishi T, Nangaku M, Shimoyama H, Inada T, Matsuyama N, Kumano H, Kuboki

Taylor-Gjevre RM, Gjevre JA, Skomro R, Nair B. (2009) Restless legs syndrome in a

patients on hemodialysis. *Am J Kidney Dis*. 2003 Apr;41(4):833-9.

rheumatoid arthritis patient cohort. *J Clin Rheumatol* 2009;15:12-15.

*Neuropathol Exp Neurol*. 2009 Nov;68(11):1193-9.

controlled pilot study. *Mov Disord*. 2004 19(12):1432-8.

paraparesis. *Eur Neurol*. 2007;57(1):31-5.

cortico-striatal neurotransmission. *Exp Neurol*. 2010 Jul;224(1):292-8. Reynolds G, Blake DR, Pall HS, Williams A. (1986) Restless leg syndrome and rheumatoid

hospital population. *Sleep Med*. 2011 Mar;12(3):295-301.

Aug;7(5):407-17.

Dec;9(6):353-61.

Jun;10(6):676-8.

May 1;23(3):349-54.

Mar;10(1):9-13.

2007 11(2):146–150.

*Rheumatol* 1994;33:60-3.

arthritis. *BMJ* 1986;292:659-60.

(2006) Efficacy and safety of pramipexole in idiopathic restless legs syndrome: a polysomnographic dose- finding study--the PRELUDE study. *Sleep Med*. 2006

related augmentation in restless legs syndrome. *Lancet Neurol*. 2006 Oct;5(10):878-86. Quinn C, Uzbeck M, Saleem I, Cotter P, Ali J, O'Malley G, Gilmartin JJ, O'Keeffe ST. (2011)

Iron status and chronic kidney disease predict restless legs syndrome in an older

adenosine A(2A) receptors with iron deficiency in rats: effects on locomotion and

movement disorder and restless legs in dialysis patients. *Nephrology (Carlton)*. 2004

neurophysiological study of restless legs syndrome in rheumatoid arthritis. *Br. J* 

pregnancy: a hospital based cross sectional survey from Pakistan*. Sleep Med*. 2009

Mitochondrial ferritin in the substantia nigra in restless legs syndrome*. J* 

syndrome (RLS) with the D2-agonist cabergoline--an open clinical trial. *Sleep*. 2000

Group. (2004) Patch application of the dopamine agonist rotigotine to patients with moderate to advanced stages of restless legs syndrome: a double-blind, placebo-

hypoechogenicity are common features in Friedreich's ataxia. *Cerebellum*. 2011

T. (2003) Clinical and psychological aspects of restless legs syndrome in uremic


Moccia M, Pellecchia MT, Erro R, Zingone F, Marelli S, Barone DG, Ciacci C, Strambi LF,

Montplaisir J, Boucher S, Poirier G, Lavigne G, Lapierre O, Lesperance P. (1997)

Montplaisir J, Nicolas A, Denesle R, Gomez-Mancilla B. (1999) Restless legs syndrome

Montplaisir J, Karrasch J, Haan J, Volc D. (2006) Ropinirole is effective in the long-term

Moreira NC, Damasceno RS, Medeiros CA, Bruin PF, Teixeira CA, Horta WG, Bruin VM.

Neau JP, Porcheron A, Mathis S, Julian A, Meurice JC, Paquereau J, Godeneche G, Ciron J,

Neau JP, Marion P, Mathis S, Julian A, Godeneche G, Larrieu D, Meurice JC, Paquereau J,

Oertel WH, Benes H, Bodenschatz R, Peglau I, Warmuth R, Happe S, Geisler P, Cassel W,

Oertel WH, Benes H, Garcia-Borreguero D, Högl B, Poewe W, Montagna P, Ferini-Strambi

Oertel W, Trenkwalder C, Beneš H, Ferini-Strambi L, Högl B, Poewe W, Stiasny-Kolster K,

O'Keeffe ST, Gavin K, Lavan JN. (1994) Iron status and restless legs syndrome in the

Phillips B, Young T, Finn L, Asher K, Hening W, Purvis C. (2000), Epidemiology of Restless

Pantaleo NP, Hening WA, Allen RP, Earley CJ. (2009) Pregnancy accounts for most of the gender difference in prevalence of familial RLS. *Sleep Med*. 2010 Mar;11(3):310-3.

Ondo W. (1999) Ropinirole for restless legs syndrome. *Mov Disord*. 1999 Jan;14(1):138-40. Ohayon MM, Roth, T. (2002) Prevalence of restless legs syndrome and periodic limb

extension study*. Lancet Neurol*. 2011 Jun 24. [Epub ahead of print]

Legs Symptoms in Adults. *Arch Intern Med*. 2000;160:2137-2141

disease. *Mov Disord*. 2010 May 15;25(7):877-81.

patients. *Braz J Med Biol Res*. 2008 Oct;41(10):932-937.

the Poitiers district, France. *Eur Neurol*. 2010; 64(5):268-74.

women before and after delivery. *Eur Neurol*. 2010;64(6):361-6.

1997;12(1):61–5.

23;52(5):938-43.

2006 Oct;21(10):1627-35.

*Neurology*. 2006 Sep 26;67(6):1040-6.

elderly. *Age Ageing* 1994;23(3):200–3.

Oct;11(9):848-56.

Barone P. (2010) Restless legs syndrome is a common feature of adult celiac

Clinical,vpolysomnographic, and genetic characteristics of restless legs syndrome: a study of 133 patients diagnosed with new standard criteria. *Mov Disord*

improved by pramipexole: a double-blind randomized trial. *Neurology*. 1999 Mar

management of restless legs syndrome: a randomized controlled trial. *Mov Disord*.

(2008) Restless legs syndrome, sleep quality and fatigue in multiple sclerosis

Bouche G. (2010) Restless legs syndrome and pregnancy: a questionnaire study in

Ingrand P. (2010) Restless legs syndrome and pregnancy: follow-up of pregnant

Leroux M, Kohnen R, Stiasny-Kolster K. (2006) Efficacy of cabergoline in restless legs syndrome: a placebo- controlled study with polysomnography (CATOR).

L, Sixel-Döring F, Trenkwalder C, Partinen M, Saletu B, Polo O, Fichtner A, Schollmayer E, Kohnen R, Cassel W, Penzel T, Stiasny-Kolster K. (2010) Rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome: a randomized, placebo-controlled polysomnographic study. *Sleep Med*. 2010

Fichtner A, Schollmayer E, Kohnen R, García- Borreguero D; on behalf of the SP710 study group. (2011) Long- term safety and efficacy of rotigotine transdermal patch for moderate-to-severe idiopathic restless legs syndrome: a 5-year open-label

movement disorder in the general population. *J Psychosom Res* 2002 Jul;53(1):547–554.


**12** 

*Japan* 

**Screening Methods for** 

**REM Sleep Behavior Disorder** 

Masayuki Miyamoto1, Tomoyuki Miyamoto2,

*1Department of Neurology, Center of Sleep Medicine, Dokkyo Medical University School of Medicine* 

Keisuke Suzuki1, Masaoki Iwanami2 and Koichi Hirata1

*2Department of Neurology Dokkyo Medical University Koshigaya Hospital* 

REM sleep behavior disorder (RBD) is a parasomnia characterized by dream-enacting behavior and vivid, action-filled or unpleasant dreams and presents a risk for self-injury and harm to others (e.g., a bed partner) due to abnormal REM sleep during which control of muscle tonus is lacking. Polysomnography is required to establish the diagnosis and represents the diagnostic gold standard for revealing loss of REM-related muscle atonia with excessive sustained or intermittent elevation of submental EMG tone or excessive phasic submental or limb EMG twitching. Idiopathic RBD (iRBD) has a male preponderance and usually emerges after the age of 50 and has a known association with neurodegenerative diseases, in particular the α-synucleinopathies such as Parkinson's disease (PD), dementia with Lewy body disease and multiple system atrophy (Schenck & Mahowald, 2002). Even more important, evidence is growing that iRBD precedes parkinsonism by years or even decades, and that iRBD might present an early stage in the development of neurodegenerative disorders (Schenck et al., 1996). Thus, to identify clinical RBD as early as possible appears to be useful for early diagnosis, a clinical trial with a potentially neuroprotective substance, and also for epidemiological studies. To meet the need for an easily applicable diagnostic screening tool, Stiasny-Kolster et al. developed and validated a specific screening scale for assessment of RBD, the RBD screening questionnaire (RBDSQ) (Stiasny-Kolster et al., 2007). Subsequently we developed a Japanese version of the RBDSQ (RBDSQ-J) after obtaining approval from the patent owner and investigated its validity and reliability (Miyamoto et al., 2009). We found that detection of RBD using the RBDSQ-J would be useful in the stepwise diagnostic process. We will discuss screening methods for RBD and describe RBD

The overall prevalence of RBD remains largely unknown. A large telephone survey using the Sleep-EVAL system for assessing violent behaviors during sleep in the general

**1. Introduction** 

screening questionnaires, including the RBDSQ-J.

**2. Prevalence of REM sleep behavior disorder** 

