ログイン
ランキング
お知らせ
ログイン
文献詳細
総説
Restless legs症候群の診断と新規治療法―Ⅰ．病態生理と診断
著者： 平田幸一1 鈴木圭輔1
所属機関： 1獨協医科大学神経内科
ページ範囲：P.1185 - P.1197
文献概要
はじめに
むずむず脚症候群はそもそもrestless legs症候群（RLS）の異訳で，日本神経学会による『神経学用語集』では下肢静止不能症候群と命名されている。17世紀に著された英国の著名な医師トーマス・ウィリス（Thomas Willis；1621-1675）の『The London Practice of Physick』における下肢の不快感による不眠の記載が初めてとされる。その後1944年カール-アクセル・エクボム（Karl-Axel Ekbom；1907-1977）により“asthenia crurum paraesthetica（irritable legs）”として初めて詳細な記述がなされ，それ以降はRLSとして報告されている1)。
RLSを正確に診断し，また治療反応性などをみるには睡眠ポリグラフ検査（polysomnography：PSG）が必要である4)。なぜならRLS患者の多くに（睡眠時）周期性四肢運動［periodic limb movement (in sleep）：PLM(S)］がみられるからである。PSGは主に睡眠中の前脛骨筋の表面筋電図によりPLMSの有無や程度をみるものである。しかし，RLSは欧米に限らずわが国でも多くの人々にみられ，いわばcommon diseaseであり，外来の第一線臨床で診断が下されなければならない。
以上の点に鑑み，2003年米国NIH（National Institute of Health）の国際RLS研究グループ（International RLS Study Group：IRLSSG）は4項目の診断基準を提唱した（Table1)5)。これはバイオマーカーなどを用いずにRLSの定義に基づき診断するものと解釈できるが，睡眠障害に関する記述は症状が日中より夕方・夜間に増強する，もしくは夕方・夜間のみに起こることの日内変動の記載があるにすぎない。
一方，睡眠障害国際分類第2版（ICSD-2）では，RLSはそもそも睡眠関連運動障害群として分類される（Table2)6)。しかし，RLSでみられる運動は睡眠関連運動障害の定義である単純で常同的なものではないが，症状発現のピークが夕方および夜であるという症状の日内変動の存在のほか，中等症以上のRLSでは睡眠障害が頻発すること，さらには多くの患者にPLMSがみられることによる。
以上より，RLSの定義は，IRLSSG診断基準に準拠するのが現実的である。すなわち，覚醒安静時および入眠時の四肢異常感覚（知覚異常）を特徴とする知覚障害であり，その症状は，発現部位の筋肉を活動させることによって軽減する。またRLSの知覚異常は脚を中心に局所的で原因不明の特発性のものが多く，発現のピークは夕方および夜である。また，多くの患者にPLMSがみられる。そしてさらに，高い確率で遺伝し，また，これらの症状はドパミンアゴニストによって緩和されるとしてよいと考えられる。本稿ではRLSの病態生理および鑑別診断，新規治療薬にも焦点を合わせて解説する。
むずむず脚症候群はそもそもrestless legs症候群（RLS）の異訳で，日本神経学会による『神経学用語集』では下肢静止不能症候群と命名されている。17世紀に著された英国の著名な医師トーマス・ウィリス（Thomas Willis；1621-1675）の『The London Practice of Physick』における下肢の不快感による不眠の記載が初めてとされる。その後1944年カール-アクセル・エクボム（Karl-Axel Ekbom；1907-1977）により“asthenia crurum paraesthetica（irritable legs）”として初めて詳細な記述がなされ，それ以降はRLSとして報告されている1)。
RLSを正確に診断し，また治療反応性などをみるには睡眠ポリグラフ検査（polysomnography：PSG）が必要である4)。なぜならRLS患者の多くに（睡眠時）周期性四肢運動［periodic limb movement (in sleep）：PLM(S)］がみられるからである。PSGは主に睡眠中の前脛骨筋の表面筋電図によりPLMSの有無や程度をみるものである。しかし，RLSは欧米に限らずわが国でも多くの人々にみられ，いわばcommon diseaseであり，外来の第一線臨床で診断が下されなければならない。
以上の点に鑑み，2003年米国NIH（National Institute of Health）の国際RLS研究グループ（International RLS Study Group：IRLSSG）は4項目の診断基準を提唱した（Table1)5)。これはバイオマーカーなどを用いずにRLSの定義に基づき診断するものと解釈できるが，睡眠障害に関する記述は症状が日中より夕方・夜間に増強する，もしくは夕方・夜間のみに起こることの日内変動の記載があるにすぎない。
一方，睡眠障害国際分類第2版（ICSD-2）では，RLSはそもそも睡眠関連運動障害群として分類される（Table2)6)。しかし，RLSでみられる運動は睡眠関連運動障害の定義である単純で常同的なものではないが，症状発現のピークが夕方および夜であるという症状の日内変動の存在のほか，中等症以上のRLSでは睡眠障害が頻発すること，さらには多くの患者にPLMSがみられることによる。
以上より，RLSの定義は，IRLSSG診断基準に準拠するのが現実的である。すなわち，覚醒安静時および入眠時の四肢異常感覚（知覚異常）を特徴とする知覚障害であり，その症状は，発現部位の筋肉を活動させることによって軽減する。またRLSの知覚異常は脚を中心に局所的で原因不明の特発性のものが多く，発現のピークは夕方および夜である。また，多くの患者にPLMSがみられる。そしてさらに，高い確率で遺伝し，また，これらの症状はドパミンアゴニストによって緩和されるとしてよいと考えられる。本稿ではRLSの病態生理および鑑別診断，新規治療薬にも焦点を合わせて解説する。
参考文献
1) Ekbom KA: Restless legs syndrome. Neurology 10: 868-873, 1960
2) American Academy of Sleep Medicine: International Classification of Sleep Disorders: Diagnostic and coding manual. 2nd ed. Westchester, 2005
3) 日本神経治療学会治療指針作成委員会: 標準的神経治療: Restless legs症候群. 神経治療学29: 71-109, 2012
4) Montplaisir J, Boucher S, Poirier G, Lavigne G, Lapierre O, et al: Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: a study of 133 patients diagnosed with new standard criteria. Mov Disord 12: 61-65, 1997
5) Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, et al: 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 4: 101-119, 2003
6) American Academy of Sleep Medicine（編), 日本睡眠学会診断分類委員会（訳): 睡眠関連運動障害群. 睡眠障害国際分類第2版 診断とコードの手引き. 医学書院, 東京, 2010, pp187-207
7) Allen RP, Walters AS, Montplaisir J, Hening W, Myers A, et al: Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 165: 1286-1292, 2005
8) Hening W, Walters AS, Allen RP, Montplaisir J, Myers A, et al: Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms, and treatment) primary care study. Sleep Med 5: 237-246, 2004
9) Rothdach AJ, Trenkwalder C, Haberstock J, Keil U, Berger K: Prevalence and risk factors of RLS in an elderly population: the MEMO study: memory and morbidity in Augsburg elderly. Neurology 54: 1064-1068, 2000
10) Allen RP, Bharmal M, Calloway M: Prevalence and disease burden of primary restless legs syndrome: results of a general population survey in the United States. Mov Disord 26: 114-120, 2011
11) Allen RP, Stillman P, Myers AJ: Physician-diagnosed restless legs syndrome in a large sample of primary medical care patients in western Europe: prevalence and characteristics. Sleep Med 11: 31-37, 2010
12) Chen NH, Chuang LP, Yang CT, Kushida CA, Hsu SC, et al: The prevalence of restless legs syndrome in Taiwanese adults. Psychiatry Clin Neurosci 64: 170-178, 2010
13) Cho SJ, Hong JP, Hahm BJ, Jeon HJ, Chang SM, et al: Restless legs syndrome in a community sample of Korean adults: prevalence, impact on quality of life, and association with DSM-IV psychiatric disorders. Sleep 32: 1069-1076, 2009
14) Kim KW, Yoon IY, Chung S, Shin YK, Lee SB, et al: Prevalence, comorbidities and risk factors of restless legs syndrome in the Korean elderly population: results from the Korean Longitudinal Study on Health and Aging. J Sleep Res 19: 87-92, 2010
15) Tan EK, Seah A, See SJ, Lim E, Wong MC, et al: Restless legs syndrome in an Asian population: a study in Singapore. Mov Disord 16: 577-579, 2001
16) Mizuno S, Miyaoka T, Inagaki T, Horiguchi J: Prevalence of restless legs syndrome in non-institutionalized Japanese elderly. Psychiatry Clin Neurosci 59: 461-465, 2005
17) Nomura T, Inoue Y, Kusumi M, Oka Y, Nakashima K: Email-based epidemiological surveys on restless legs syndrome in Japan. Sleep Biol Rhythms 6: 139-145, 2008
18) Nomura T, Inoue Y, Kusumi M, Uemura Y, Nakashima K: Prevalence of restless legs syndrome in a rural community in Japan. Mov Disord 23: 2363-2369, 2008
19) Tsuboi Y, Imamura A, Sugimura M, Nakano S, Shirakawa S, et al: Prevalence of restless legs syndrome in a Japanese elderly population. Parkinsonism Relat Disord 15: 598-601, 2009
20) Walters AS, Hickey K, Maltzman J, Verrico T, Joseph D, et al: A questionnaire study of 138 patients with restless legs syndrome: the 'Night-Walkers' survey. Neurology 46: 92-95, 1996
21) Winkelmann J, Schormair B, Lichtner P, Ripke S, Xiong L, et al: Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet 39: 1000-1006, 2007
22) Paulus W, Dowling P, Rijsman R, Stiasny-Kolster K, Trenkwalder C: Update of the pathophysiology of the restless-legs-syndrome. Mov Disord 22(Suppl 18): S431-439, 2007
23) Schormair B, Plag J, Kaffe M, Gross N, Czamara D, et al: MEIS1 and BTBD9: genetic association with restless leg syndrome in end stage renal disease. J Med Genet 48: 462-466, 2011
24) Avidan AY: Neurologic disorders: restless legs syndrome and periodic limb mobements in sleep. Kryger MH (ed): Atlas of Clinical Sleep Medicine. Saunders, Philadelphia, 2009, pp115-124
25) Philipsen A, Hornyak M, Riemann D: Sleep and sleep disorders in adults with attention deficit/hyperactivity disorder. Sleep Med Rev 10: 399-405, 2006
26) Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, et al: Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med 4: 121-132, 2003
27) 宮本雅之, 宮本智之, 井上雄一, 清水徹男: 睡眠障害の診断・治療ガイドライン：睡眠関連運動障害（SRMD）の診断・治療・連携ガイドライン. 睡眠医療2: 290-295, 2008
28) Montplaisir J, Boucher S, Nicolas A, Lesperance P, Gosselin A, et al: Immobilization tests and periodic leg movements in sleep for the diagnosis of restless leg syndrome. Mov Disord 13: 324-329, 1998
29) Inoue Y, Hirata K, Kuroda K, Fujita M, Shimizu T, et al: Efficacy and safety of pramipexole in Japanese patients with primary restless legs syndrome: a polysomnographic randomized, double-blind, placebo-controlled study. Sleep Med 11: 11-16, 2010
30) De Cock VC, Bayard S, Yu H, Grini M, Carlander B, et al: Suggested immobilization test for diagnosis of restless legs syndrome in Parkinson's disease. Mov Disord 27: 743-749, 2012
31) Kushida CA: Clinical presentation, diagnosis, and quality of life issues in restless legs syndrome. Am J Med 120: S4-S12, 2007
32) Garcia-Borreguero D, Stillman P, Benes H, Buschmann H, Chaudhuri KR, et al: Algorithms for the diagnosis and treatment of restless legs syndrome in primary care. BMC Neurol 11: 28, 2011
33) 宮本雅之, 平田幸一, 鈴木圭輔, 宮本智之: 睡眠関連運動障害. 最新精神医学16: 673-682, 2011
34) Hening WA, Allen RP, Washburn M, Lesage SR, Earley CJ: The four diagnostic criteria for restless legs syndrome are unable to exclude confounding conditions ("mimics"). Sleep Med 10: 976-981, 2009
35) Allen RP, Earley CJ: The role of iron in restless legs syndrome. Mov Disord 22(Suppl 18): S440-448, 2007
36) Clemens S, Rye D, Hochman S: Restless legs syndrome: revisiting the dopamine hypothesis from the spinal cord perspective. Neurology 67: 125-130, 2006
37) Trenkwalder C, Hening WA, Walters AS, Campbell SS, Rahman K, et al: Circadian rhythm of periodic limb movements and sensory symptoms of restless legs syndrome. Mov Disord 14: 102-110, 1999
38) Earley CJ, Connor JR, Beard JL, Malecki EA, Epstein DK, et al: Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology 54: 1698-1700, 2000
39) Mizuno S, Mihara T, Miyaoka T, Inagaki T, Horiguchi J: CSF iron, ferritin and transferrin levels in restless legs syndrome. J Sleep Res 14: 43-47, 2005
40) Allen RP, Barker PB, Wehrl F, Song HK, Earley CJ: MRI measurement of brain iron in patients with restless legs syndrome. Neurology 56: 263-265, 2001
41) Schmidauer C, Sojer M, Seppi K, Stockner H, Hogl B, et al: Transcranial ultrasound shows nigral hypoechogenicity in restless legs syndrome. Ann Neurol 58: 630-634, 2005
42) Connor JR, Boyer PJ, Menzies SL, Dellinger B, Allen RP, et al: Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome. Neurology 61: 304-309, 2003
43) Wetter TC, Eisensehr I, Trenkwalder C: Functional neuroimaging studies in restless legs syndrome. Sleep Med 5: 401-406, 2004
44) Eisensehr I, Wetter TC, Linke R, Noachtar S, von Lindeiner H, et al: Normal IPT and IBZM SPECT in drug-naive and levodopa-treated idiopathic restless legs syndrome. Neurology 57: 1307-1309, 2001
C-raclopride PET studies. Neurology 52: 932-937, 1999
46) Ruottinen HM, Partinen M, Hublin C, Bergman J, Haaparanta M, et al: An FDOPA PET study in patients with periodic limb movement disorder and restless legs syndrome. Neurology 54: 502-504, 2000
47) Trenkwalder C, Walters AS, Hening WA, Chokroverty S, Antonini A, et al: Positron emission tomographic studies in restless legs syndrome. Mov Disord 14: 141-145, 1999
48) Stoessl AJ, Brooks DJ, Eidelberg D: Milestones in neuroimaging. Mov Disord 26: 868-978, 2011
49) Michaud M, Soucy JP, Chabli A, Lavigne G, Montplaisir J: SPECT imaging of striatal pre- and postsynaptic dopaminergic status in restless legs syndrome with periodic leg movements in sleep. J Neurol 249: 164-170, 2002
50) Mrowka M, Jobges M, Berding G, Schimke N, Shing M, et al: Computerized movement analysis and beta-CIT-SPECT in patients with restless legs syndrome. J Neural Transm 112: 693-701, 2005
51) Earley CJ, Kuwabara H, Wong DF, Gamaldo C, Salas R, et al: The dopamine transporter is decreased in the striatum of subjects with restless legs syndrome. Sleep 34: 341-347, 2011
52) Connor JR, Wang XS, Allen RP, Beard JL, Wiesinger JA, et al: Altered dopaminergic profile in the putamen and substantia nigra in restless leg syndrome. Brain 132: 2403-2412, 2009
53) Telles SC, Alves RC, Chadi G: Periodic limb movements during sleep and restless legs syndrome in patients with ASIA A spinal cord injury. J Neurol Sci 303: 119-123, 2011
54) Högl B, Frauscher B, Seppi K, Ulmer H, Poewe W: Transient restless legs syndrome after spinal anesthesia: a prospective study. Neurology 59: 1705-1707, 2002
55) Ferreri F, Rossini PM: Neurophysiological investigations in restless legs syndrome and other disorders of movement during sleep. Sleep Med 5: 397-399, 2004
56) Tergau F, Wischer S, Paulus W: Motor system excitability in patients with restless legs syndrome. Neurology 52: 1060-1063, 1999
57) Quatrale R, Manconi M, Gastaldo E, Eleopra R, Tugnoli V, et al: Neurophysiological study of corticomotor pathways in restless legs syndrome. Clin Neurophysiol 114: 1638-1645, 2003
58) Terzano MG, Parrino L: Origin and significance of the cyclic alternating pattern (CAP): review article. Sleep Med Rev 4: 101-123, 2000
59) Bara-Jimenez W, Aksu M, Graham B, Sato S, Hallett M: Periodic limb movements in sleep: state-dependent excitability of the spinal flexor reflex. Neurology 54: 1609-1616, 2000
60) Bucher SF, Seelos KC, Oertel WH, Reiser M, Trenkwalder C: Cerebral generators involved in the pathogenesis of the restless legs syndrome. Ann Neurol 41: 639-645, 1997
61) de Weerd AW, Rijsman RM, Brinkley A: Activity patterns of leg muscles in periodic limb movement disorder. J Neurol Neurosurg Psychiatry 75: 317-319, 2004
62) Rye DB: The two faces of Eve: dopamine's modulation of wakefulness and sleep. Neurology 63: S2-S7, 2004
63) Levant B, McCarson KE: D(3) dopamine receptors in rat spinal cord: implications for sensory and motor function. Neurosci Lett 303: 9-12, 2001
64) Inoue Y, Kuroda K, Hirata K, Uchimura N, Kagimura T, et al: Long-term open-label study of pramipexole in patients with primary restless legs syndrome. J Neurol Sci 294: 62-66, 2010
65) Gladwell SJ, Coote JH: Inhibitory and indirect excitatory effects of dopamine on sympathetic preganglionic neurones in the neonatal rat spinal cord in vitro. Brain Res 818: 397-407, 1999
66) Robinson SE, Austin MJ, Gibbens DM: The role of serotonergic neurons in dorsal raphe, median raphe and anterior hypothalamic pressor mechanisms. Neuropharmacology 24: 51-58, 1985
67) Barker D, Saito M: Autonomic innervation of receptors and muscle fibres in cat skeletal muscle. Proc R Soc Lond B Biol Sci 212: 317-332, 1981
68) Seagrove LC, Suzuki R, Dickenson AH: Electrophysiological characterisations of rat lamina I dorsal horn neurones and the involvement of excitatory amino acid receptors. Pain 108: 76-87, 2004
69) Meyerson BA, Linderoth B: Mechanisms of spinal cord stimulation in neuropathic pain. Neurol Res 22: 285-292, 2000
70) Melzack R: Pain: past, present and future. Can J Exp Psychol 47: 615-629, 1993
71) Schilling C, Schredl M, Strobl P, Deuschle M: Restless legs syndrome: evidence for nocturnal hypothalamic-pituitary-adrenal system activation. Mov Disord 25: 1047-1052, 2010
72) Walters AS, Rye DB: Review of the relationship of restless legs syndrome and periodic limb movements in sleep to hypertension, heart disease, and stroke. Sleep 32: 589-597, 2009
73) Takada M, Li ZK, Hattori T: Single thalamic dopaminergic neurons project to both the neocortex and spinal cord. Brain Res 455: 346-352, 1988
74) Allen RP, Barker PB, Horska A, Earley CJ: Thalamic glutamate/glutamine in restless legs syndrome: increased and related to disturbed sleep. Neurology 80: 2028-2034, 2013
75) Ondo WG: Movements mimicking myoclonus Associated with spinal cord pathology: is this a "pure motor restless legs syndrome". Tremor Other Hyperkinet Mov (N Y) ［Epub 2012 Mar 20］
76) Schürks M, Bussfeld P: Multiple sclerosis and restless legs syndrome: a systematic review and meta-analysis. Eur J Neurol 20: 605-615, 2013
77) Abele M, Burk K, Laccone F, Dichgans J, Klockgether T: Restless legs syndrome in spinocerebellar ataxia types 1, 2, and 3．J Neurol 248: 311-314, 2001
78) Ondo WG, Lai D: Association between restless legs syndrome and essential tremor. Mov Disord 21: 515-518, 2006
79) Polydefkis M, Allen RP, Hauer P, Earley CJ, Griffin JW, et al: Subclinical sensory neuropathy in late-onset restless legs syndrome. Neurology 55: 1115-1121, 2000
80) Salvi F, Montagna P, Plasmati R, Rubboli G, Cirignotta F, et al: Restless legs syndrome and nocturnal myoclonus: initial clinical manifestation of familial amyloid polyneuropathy. J Neurol Neurosurg Psychiatry 53: 522-525, 1990
81) Gemignani F, Marbini A, Di Giovanni G, Salih S, Margarito FP, et al: Cryoglobulinaemic neuropathy manifesting with restless legs syndrome. J Neurol Sci 152: 218-223, 1997
82) Iannaccone S, Quattrini A, Sferrazza B, Ferini-Strambi L: Charcot-Marie-Tooth disease type 2 with restless legs syndrome. Neurology 54: 1013-1014, 2000
83) Gemignani F, Brindani F, Negrotti A, Vitetta F, Alfieri S, et al: Restless legs syndrome and polyneuropathy. Mov Disord 21: 1254-1257, 2006
84) Stiasny-Kolster K, Magerl W, Oertel WH, Moller JC, Treede RD: Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome. Brain 127: 773-782, 2004
85) Stiasny-Kolster K, Pfau DB, Oertel WH, Treede RD, Magerl W: Hyperalgesia and functional sensory loss in restless legs syndrome. Pain 154: 1457-1463, 2013
86) Hanna PA, Kumar S, Walters AS: Restless legs symptoms in a patient with above knee amputations: a case of phantom restless legs. Clin Neuropharmacol 27: 87-89, 2004
87) Iranzo A, Comella CL, Santamaria J, Oertel W: Restless legs syndrome in Parkinson's disease and other neurodegenerative diseases of the central nervous system. Mov Disord 22(Suppl 18): S424-430, 2007
88) Möller JC, Unger M, Stiasny-Kolster K, Oertel WH: Restless legs syndrome (RLS) and Parkinson's disease (PD)-related disorders or different entities? J Neurol Sci 289: 135-137, 2010
89) Nomura T, Inoue Y, Miyake M, Yasui K, Nakashima K: Prevalence and clinical characteristics of restless legs syndrome in Japanese patients with Parkinson's disease. Mov Disord 21: 380-384, 2006
90) Lee JE, Shin HW, Kim KS, Sohn YH: Factors contributing to the development of restless legs syndrome in patients with Parkinson disease. Mov Disord 24: 579-582, 2009
91) Angelini M, Negrotti A, Marchesi E, Bonavina G, Calzetti S: A study of the prevalence of restless legs syndrome in previously untreated Parkinson's disease patients: absence of co-morbid association. J Neurol Sci 310: 286-288, 2011
92) Gjerstad MD, Tysnes OB, Larsen JP: Increased risk of leg motor restlessness but not RLS in early Parkinson disease. Neurology 77: 1941-1946, 2011
93) Suzuki K, Miyamoto M, Miyamoto T, Tatsumoto M, Watanabe Y, et al: Nocturnal disturbances and restlessness in Parkinson's disease: using the Japanese version of the Parkinson's disease sleep scale-2．J Neurol Sci 318: 76-81, 2012
94) Shimohata T, Nishizawa M: Sleep disturbance in patients with Parkinson's disease presenting with leg motor restlessness. Parkinsonism Relat Disord 19: 571-572, 2013
95) Rains JC, Poceta JS: Sleep and headache. Curr Treat Options Neurol 12: 1-15, 2010
96) d'Onofrio F, Cologno D, Petretta V, Finocchi C, Autunno M, et al: Restless legs syndrome is not associated with migraine with aura: a clinical study. Neurol Sci 32(Suppl 1): S153-S156, 2011
97) Chen PK, Fuh JL, Chen SP, Wang SJ: Association between restless legs syndrome and migraine. J Neurol Neurosurg Psychiatry 81: 524-528, 2010
98) Rhode AM, Hosing VG, Happe S, Biehl K, Young P, et al: Comorbidity of migraine and restless legs syndrome: a case-control study. Cephalalgia 27: 1255-1260, 2007
99) Suzuki S, Suzuki K, Miyamoto M, Miyamoto T, Watanabe Y, et al: Evaluation of contributing factors to restless legs syndrome in migraine patients. J Neurol 258: 2026-2035, 2011
100) Schürks M, Winter AC, Berger K, Buring JE, Kurth T: Migraine and restless legs syndrome in women. Cephalalgia 32: 382-389, 2012
101) Winter AC, Schürks M, Berger K, Buring JE, Gaziano JM, et al: Migraine and restless legs syndrome in men. Cephalalgia 33: 130-135, 2013
102) Charbit AR, Akerman S, Goadsby PJ: Dopamine: what's new in migraine? Curr Opin Neurol 23: 275-281, 2010
103) Suzuki K, Suzuki S, Miyamoto M, Miyamoto T, Numao A, et al: Does pramipexole treatment improve headache in patients with concomitant migraine and restless legs syndrome? Tremor Other Hyperkinet Mov (N Y), 2013 (in press)
掲載誌情報
