Abstract
Nocturnal symptoms are frequent in Parkinson disease (PD) and consist of nocturnal sleep disorders such as REM sleep behavior disorder (RBD) and restless legs syndrome. There is an increasing need for reliable, early, pre-motor diagnosis of PD, since motor symptoms occur when there is already significant neuronal loss. Recent prospective studies have shown that over 80 % of idiopathic RBD patients over time converted to PD and related synucleinopathies. RBD patients have autonomic, visual, and olfactory dysfunction as well as neuroimaging abnormalities similar to those seen in PD. Studies have shown that neuroimaging abnormalities and visual and olfactory dysfunction can help predict which RBD patients will likely convert to a neurodegenerative diagnosis within a short follow-up period. These factors make RBD an ideal population for prediction to PD conversion, allowing future testing and eventual use of neuroprotective strategies.
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Abbott RD, Petrovitch H, White LR, Masaki KH, Tanner CM, Curb JD, Grandinetti A, Blanchette PL, Popper JS, Ross GW (2001) Frequency of bowel movements and the future risk of Parkinson’s disease. Neurology 57(3):456–462
Abbott RD, Ross GW, White LR, Tanner CM, Masaki KH, Nelson JS, Curb JD, Petrovitch H (2005) Excessive daytime sleepiness and subsequent development of Parkinson disease. Neurology 65(9):1442–1446. doi:10.1212/01.wnl.0000183056.89590.0d
Albin RL, Koeppe RA, Chervin RD, Consens FB, Wernette K, Frey KA, Aldrich MS (2000) Decreased striatal dopaminergic innervation in REM sleep behavior disorder. Neurology 55(9):1410–1412
Allen RP, Barker PB, Wehrl F, Song HK, Earley CJ (2001) MRI measurement of brain iron in patients with restless legs syndrome. Neurology 56(2):263–265
Allen RP, Walters AS, Montplaisir J, Hening W, Myers A, Bell TJ, Ferini-Strambi L (2005) Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 165(11):1286–1292
Berg D, Godau J, Walter U (2008) Transcranial sonography in movement disorders. Lancet Neurol 7(11):1044–1055. doi:10.1016/S1474-4422(08)70239-4
Berg D, Lang AE, Postuma RB, Maetzler W, Deuschl G, Gasser T, Siderowf A, Schapira AH, Oertel W, Obeso JA, Olanow CW, Poewe W, Stern M (2013) Changing the research criteria for the diagnosis of Parkinson’s disease: obstacles and opportunities. Lancet Neurol 12(5):514–524. doi:10.1016/S1474-4422(13)70047-4
Biousse V, Skibell BC, Watts RL, Loupe DN, Drews-Botsch C, Newman NJ (2004) Ophthalmologic features of Parkinson’s disease. Neurology 62(2):177–180
Boeve BF (2013) Idiopathic REM sleep behaviour disorder in the development of Parkinson’s disease. Lancet Neurol 12(5):469–482. doi:10.1016/S1474-4422(13)70054-1
Boeve BF, Molano JR, Ferman TJ, Smith GE, Lin SC, Bieniek K, Haider W, Tippmann-Peikert M, Knopman DS, Graff-Radford NR, Lucas JA, Petersen RC, Silber MH (2011) Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in an aging and dementia cohort. Sleep Med 12(5):445–453
Boeve BF, Silber MH, Ferman TJ, Lin SC, Benarroch EE, Schmeichel AM, Ahlskog JE, Caselli RJ, Jacobson S, Sabbagh M, Adler C, Woodruff B, Beach TG, Iranzo A, Gelpi E, Santamaria J, Tolosa E, Singer C, Mash DC, Luca C, Arnulf I, Duyckaerts C, Schenck CH, Mahowald MW, Dauvilliers Y, Graff-Radford NR, Wszolek ZK, Parisi JE, Dugger B, Murray ME, Dickson DW (2013) Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. Sleep Med 14(8):754–762. doi:10.1016/j.sleep.2012.10.015
Booij J, Tissingh G, Boer GJ, Speelman JD, Stoof JC, Janssen AG, Wolters EC, van Royen EA (1997) [123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson’s disease. J Neurol Neurosurg Psychiatry 62(2):133–140
Boot BP, Boeve BF, Roberts RO, Ferman TJ, Geda YE, Pankratz VS, Ivnik RJ, Smith GE, McDade E, Christianson TJ, Knopman DS, Tangalos EG, Silber MH, Petersen RC (2012) Probable rapid eye movement sleep behavior disorder increases risk for mild cognitive impairment and Parkinson disease: a population-based study. Ann Neurol 71(1):49–56. doi:10.1002/ana.22655
Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24(2):197–211
Calzetti S, Negrotti A, Bonavina G, Angelini M, Marchesi E (2009) Absence of co-morbidity of Parkinson disease and restless legs syndrome: a case-control study in patients attending a movement disorders clinic. Neurol Sci 30(2):119–122. doi:10.1007/s10072-009-0037-7
Cervenka S, Palhagen SE, Comley RA, Panagiotidis G, Cselenyi Z, Matthews JC, Lai RY, Halldin C, Farde L (2006) Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on D2-receptor binding. Brain 129(Pt 8):2017–2028
Claassen DO, Josephs KA, Ahlskog JE, Silber MH, Tippmann-Peikert M, Boeve BF (2010) REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century. Neurology 75(6):494–499. doi:10.1212/WNL.0b013e3181ec7fac
Compta Y, Santamaria J, Ratti L, Tolosa E, Iranzo A, Munoz E, Valldeoriola F, Casamitjana R, Rios J, Marti MJ (2009) Cerebrospinal hypocretin, daytime sleepiness and sleep architecture in Parkinson’s disease dementia. Brain 132(Pt 12):3308–3317. doi:10.1093/brain/awp263
De Cock VC, Vidailhet M, Arnulf I (2008) Sleep disturbances in patients with parkinsonism. Nat Clin Pract Neurol 4(5):254–266. doi:10.1038/ncpneuro0775
Drouot X, Moutereau S, Nguyen JP, Lefaucheur JP, Creange A, Remy P, Goldenberg F, d’Ortho MP (2003) Low levels of ventricular CSF orexin/hypocretin in advanced PD. Neurology 61(4):540–543
Eisensehr I, Wetter TC, Linke R, Noachtar S, von Lindeiner H, Gildehaus FJ, Trenkwalder C, Tatsch K (2001) Normal IPT and IBZM SPECT in drug-naive and levodopa-treated idiopathic restless legs syndrome. Neurology 57(7):1307–1309
Fronczek R, Overeem S, Lee SY, Hegeman IM, van Pelt J, van Duinen SG, Lammers GJ, Swaab DF (2007) Hypocretin (orexin) loss in Parkinson’s disease. Brain 130(Pt 6):1577–1585. doi:10.1093/brain/awm090
Gagnon JF, Vendette M, Postuma RB, Desjardins C, Massicotte-Marquez J, Panisset M, Montplaisir J (2009) Mild cognitive impairment in rapid eye movement sleep behavior disorder and Parkinson’s disease. Ann Neurol 66(1):39–47. doi:10.1002/ana.21680
Gagnon JF, Bertrand JA, Genier Marchand D (2012) Cognition in rapid eye movement sleep behavior disorder. Front Neurol 3:82. doi:10.3389/fneur.2012.00082
Gao X, Schwarzschild MA, O’Reilly EJ, Wang H, Ascherio A (2010) Restless legs syndrome and Parkinson’s disease in men. Mov Disord 25(15):2654–2657. doi:10.1002/mds.23256
Gao J, Huang X, Park Y, Hollenbeck A, Blair A, Schatzkin A, Chen H (2011) Daytime napping, nighttime sleeping, and Parkinson disease. Am J Epidemiol 173(9):1032–1038. doi:10.1093/aje/kwq478
Godau J, Sojer M (2010) Transcranial sonography in restless legs syndrome. Int Rev Neurobiol 90:199–215. doi:10.1016/S0074-7742(10)90015-9
Haehner A, Boesveldt S, Berendse HW, Mackay-Sim A, Fleischmann J, Silburn PA, Johnston AN, Mellick GD, Herting B, Reichmann H, Hummel T (2009) Prevalence of smell loss in Parkinson’s disease—a multicenter study. Parkinsonism Relat Disord 15(7):490–494. doi:10.1016/j.parkreldis.2008.12.005
Hagell P, Broman JE (2007) Measurement properties and hierarchical item structure of the Epworth sleepiness scale in Parkinson’s disease. J Sleep Res 16(1):102–109
Hobson DE, Lang AE, Martin WR, Razmy A, Rivest J, Fleming J (2002) Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease: a survey by the Canadian Movement Disorders Group. JAMA 287(4):455–463
Iranzo A, Molinuevo JL, Santamaria J, Serradell M, Marti MJ, Valldeoriola F, Tolosa E (2006) Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol 5(7):572–577. doi:10.1016/S1474-4422(06)70476-8
Iranzo A, Lomena F, Stockner H, Valldeoriola F, Vilaseca I, Salamero M, Molinuevo JL, Serradell M, Duch J, Pavia J, Gallego J, Seppi K, Hogl B, Tolosa E, Poewe W, Santamaria J, Sleep Innsbruck Barcelona Group (2010) Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study corrected. Lancet Neurol 9(11):1070–1077. doi:10.1016/S1474-4422(10)70216-7
Iranzo A, Valldeoriola F, Lomena F, Molinuevo JL, Serradell M, Salamero M, Cot A, Ros D, Pavia J, Santamaria J, Tolosa E (2011) Serial dopamine transporter imaging of nigrostriatal function in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. Lancet Neurol 10(9):797–805. doi:10.1016/S1474-4422(11)70152-1
Iranzo A, Tolosa E, Gelpi E, Molinuevo JL, Valldeoriola F, Serradell M, Sanchez-Valle R, Vilaseca I, Lomena F, Vilas D, Llado A, Gaig C, Santamaria J (2013) Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. Lancet Neurol 12(5):443–453. doi:10.1016/S1474-4422(13)70056-5
Iwanami M, Miyamoto T, Miyamoto M, Hirata K, Takada E (2010) Relevance of substantia nigra hyperechogenicity and reduced odor identification in idiopathic REM sleep behavior disorder. Sleep Med 11(4):361–365. doi:10.1016/j.sleep.2009.12.006
Leentjens AF, Van der Akker M, Metsemakers JF, Lousberg R, Verhey FR (2003) Higher incidence of depression preceding the onset of Parkinson’s disease: a register study. Mov Disord 18(4):414–418
Loo HV, Tan EK (2008) Case-control study of restless legs syndrome and quality of sleep in Parkinson’s disease. J Neurol Sci 266(1–2):145–149. doi:10.1016/j.jns.2007.09.033
Miyamoto T, Miyamoto M, Inoue Y, Usui Y, Suzuki K, Hirata K (2006) Reduced cardiac 123I-MIBG scintigraphy in idiopathic REM sleep behavior disorder. Neurology 67(12):2236–2238. doi:10.1212/01.wnl.0000249313.25627.2e
Miyamoto T, Miyamoto M, Iwanami M, Hirata K (2010) Olfactory dysfunction in Japanese patients with idiopathic REM sleep behavior disorder: comparison of data using the University of Pennsylvania smell identification test and odor stick identification test for Japanese. Mov Disord 25(10):1524–1526. doi:10.1002/mds.23170
Mollenhauer B, Trautmann E, Sixel-Doring F, Wicke T, Ebentheuer J, Schaumburg M, Lang E, Focke NK, Kumar KR, Lohmann K, Klein C, Schlossmacher MG, Kohnen R, Friede T, Trenkwalder C, DeNoPa Study Group (2013) Nonmotor and diagnostic findings in subjects with de novo Parkinson disease of the DeNoPa cohort. Neurology 81(14):1226–1234. doi:10.1212/WNL.0b013e3182a6cbd5
Nomura T, Inoue Y, Miyake M, Yasui K, Nakashima K (2006) Prevalence and clinical characteristics of restless legs syndrome in Japanese patients with Parkinson’s disease. Mov Disord 21(3):380–384. doi:10.1002/mds.20734
Pacchetti C, Manni R, Zangaglia R, Mancini F, Marchioni E, Tassorelli C, Terzaghi M, Ossola M, Martignoni E, Moglia A, Nappi G (2005) Relationship between hallucinations, delusions, and rapid eye movement sleep behavior disorder in Parkinson’s disease. Mov Disord 20(11):1439–1448. doi:10.1002/mds.20582
Parkinson J (2002) An essay on the shaking palsy. 1817. J Neuropsychiatry Clin Neurosci 14(2):223–236 (Discussion 222)
Pittock SJ, Parrett T, Adler CH, Parisi JE, Dickson DW, Ahlskog JE (2004) Neuropathology of primary restless leg syndrome: absence of specific tau- and alpha-synuclein pathology. Mov Disord 19(6):695–699. doi:10.1002/mds.20042
Postuma RB, Lang AE, Massicotte-Marquez J, Montplaisir J (2006) Potential early markers of Parkinson disease in idiopathic REM sleep behavior disorder. Neurology 66(6):845–851. doi:10.1212/01.wnl.0000203648.80727.5b
Postuma RB, Gagnon JF, Vendette M, Charland K, Montplaisir J (2008a) Manifestations of Parkinson disease differ in association with REM sleep behavior disorder. Mov Disord 23(12):1665–1672. doi:10.1002/mds.22099
Postuma RB, Gagnon JF, Vendette M, Charland K, Montplaisir J (2008b) REM sleep behaviour disorder in Parkinson’s disease is associated with specific motor features. J Neurol Neurosurg Psychiatry 79(10):1117–1121. doi:10.1136/jnnp.2008.149195
Postuma RB, Gagnon JF, Vendette M, Fantini ML, Massicotte-Marquez J, Montplaisir J (2009a) Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology 72(15):1296–1300. doi:10.1212/01.wnl.0000340980.19702.6e
Postuma RB, Gagnon JF, Vendette M, Montplaisir JY (2009b) Markers of neurodegeneration in idiopathic rapid eye movement sleep behaviour disorder and Parkinson’s disease. Brain 132(Pt 12):3298–3307. doi:10.1093/brain/awp244
Postuma RB, Gagnon JF, Rompre S, Montplaisir JY (2010a) Severity of REM atonia loss in idiopathic REM sleep behavior disorder predicts Parkinson disease. Neurology 74(3):239–244. doi:10.1212/WNL.0b013e3181ca0166
Postuma RB, Lanfranchi PA, Blais H, Gagnon JF, Montplaisir JY (2010b) Cardiac autonomic dysfunction in idiopathic REM sleep behavior disorder. Mov Disord 25(14):2304–2310. doi:10.1002/mds.23347
Postuma RB, Gagnon JF, Vendette M, Desjardins C, Montplaisir JY (2011) Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder. Ann Neurol 69(5):811–818. doi:10.1002/ana.22282
Postuma RB, Bertrand JA, Montplaisir J, Desjardins C, Vendette M, Rios Romenets S, Panisset M, Gagnon JF (2012a) Rapid eye movement sleep behavior disorder and risk of dementia in Parkinson’s disease: a prospective study. Mov Disord 27(6):720–726. doi:10.1002/mds.24939
Postuma RB, Lang AE, Gagnon JF, Pelletier A, Montplaisir JY (2012b) How does parkinsonism start? Prodromal parkinsonism motor changes in idiopathic REM sleep behaviour disorder. Brain 135(Pt 6):1860–1870. doi:10.1093/brain/aws093
Romenets SR, Gagnon JF, Latreille V, Panniset M, Chouinard S, Montplaisir J, Postuma RB (2012) Rapid eye movement sleep behavior disorder and subtypes of Parkinson’s disease. Mov Disord 27(8):996–1003. doi:10.1002/mds.25086
Schenck CH, Bundlie SR, Mahowald MW (1996) Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology 46(2):388–393
Schenck CH, Boeve BF, Mahowald MW (2013) Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med 14(8):744–748. doi:10.1016/j.sleep.2012.10.009
Shin HY, Joo EY, Kim ST, Dhong HJ, Cho JW (2013) Comparison study of olfactory function and substantia nigra hyperechogenicity in idiopathic REM sleep behavior disorder, Parkinson’s disease and normal control. Neurol Sci 34(6):935–940. doi:10.1007/s10072-012-1164-0
Siegel JM (2006) The stuff dreams are made of: anatomical substrates of REM sleep. Nat Neurosci 9(6):721–722. doi:10.1038/nn0606-721
Stiasny-Kolster K, Mayer G, Schafer S, Moller JC, Heinzel-Gutenbrunner M, Oertel WH (2007) The REM sleep behavior screening questionnaire—a new diagnostic instrument. Mov Disord 22(16):2386–2393
Stockner H, Iranzo A, Seppi K, Serradell M, Gschliesser V, Sojer M, Valldeoriola F, Molinuevo JL, Frauscher B, Schmidauer C, Santamaria J, Hogl B, Tolosa E, Poewe W, Sleep Innsbruck Barcelona Group (2009) Midbrain hyperechogenicity in idiopathic REM sleep behavior disorder. Mov Disord 24(13):1906–1909. doi:10.1002/mds.22483
Thannickal TC, Lai YY, Siegel JM (2007) Hypocretin (orexin) cell loss in Parkinson’s disease. Brain 130(Pt 6):1586–1595. doi:10.1093/brain/awm097
Trenkwalder C, Walters AS, Hening WA, Chokroverty A, Antonini A, Dhawan V, Eidelberg D (1999) Positron emission tomographic studies in restless legs syndrome. Mov Disord 14(1):141–145
Turjanski N, Lees AJ, Brooks DJ (1999) Striatal dopaminergic function in restless legs syndrome: 18F-dopa and 11C-raclopride PET studies. Neurology 52(5):932–937
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Slow, E.J., Postuma, R.B. & Lang, A.E. Implications of nocturnal symptoms towards the early diagnosis of Parkinson’s disease. J Neural Transm 121 (Suppl 1), 49–57 (2014). https://doi.org/10.1007/s00702-014-1168-4
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DOI: https://doi.org/10.1007/s00702-014-1168-4