Skip to main content

Advertisement

SpringerLink
Log in

Neurofilament light chain and cardiac MIBG uptake as predictors for phenoconversion in isolated REM sleep behavior disorder

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Background

Isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD) is considered as a prodromal stage of either multiple system atrophy (MSA) or Lewy body disease (LBD; Parkinson's disease and dementia with Lewy bodies). However, current knowledge is limited in predicting and differentiating the type of future phenoconversion in iRBD patients. We investigated the role of plasma neurofilament light chain (NfL) and cardiac metaiodobenzylguanidine (MIBG) uptake as predictors for phenoconversion.

Methods

Forty patients with iRBD were enrolled between April 2018 and October 2019 and prospectively followed every 3 months to determine phenoconversion to either MSA or LBD. Plasma NfL levels were measured at enrollment. Cardiac MIBG uptake and striatal dopamine transporter uptake were assessed at baseline.

Results

Patients were followed for a median of 2.92 years. Four patients converted to MSA and 7 to LBD. Plasma NfL level at baseline was significantly higher in future MSA-converters (median 23.2 pg/mL) when compared with the rest of the samples (median 14.1 pg/mL, p = 0.003). NfL level above 21.3 pg/mL predicted phenoconversion to MSA with the sensitivity of 100% and specificity of 94.3%. Baseline MIBG heart-to-mediastinum ratio of LBD-converters (median 1.10) was significantly lower when compared with the rest (median 2.00, p < 0.001). Heart-to-mediastinum ratio below 1.545 predicted phenoconversion to LBD with the sensitivity of 100% and specificity of 92.9%.

Conclusions

Plasma NfL and cardiac MIBG uptake may be useful biomarkers in predicting phenoconversion of iRBD. Elevated plasma NfL levels may suggest imminent phenoconversion to MSA, whereas low cardiac MIBG uptake suggests phenoconversion to LBD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

References

  1. Postuma RB, Iranzo A, Hu M, Högl B, Boeve BF, Manni R, Oertel WH, Arnulf I, Ferini-Strambi L, Puligheddu M, Antelmi E, Cochen De Cock V, Arnaldi D, Mollenhauer B, Videnovic A, Sonka K, Jung KY, Kunz D, Dauvilliers Y, Provini F, Lewis SJ, Buskova J, Pavlova M, Heidbreder A, Montplaisir JY, Santamaria J, Barber TR, Stefani A, St Louis EK, Terzaghi M, Janzen A, Leu-Semenescu S, Plazzi G, Nobili F, Sixel-Doering F, Dusek P, Bes F, Cortelli P, Ehgoetz Martens K, Gagnon JF, Gaig C, Zucconi M, Trenkwalder C, Gan-Or Z, Lo C, Rolinski M, Mahlknecht P, Holzknecht E, Boeve AR, Teigen LN, Toscano G, Mayer G, Morbelli S, Dawson B, Pelletier A (2019) Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain 142:744–759. https://doi.org/10.1093/brain/awz030

    Article  PubMed  PubMed Central  Google Scholar 

  2. Iranzo A, Fernandez-Arcos A, Tolosa E, Serradell M, Molinuevo JL, Valldeoriola F, Gelpi E, Vilaseca I, Sanchez-Valle R, Llado A, Gaig C, Santamaria J (2014) Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients. PLoS ONE 9:e89741. https://doi.org/10.1371/journal.pone.0089741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Miglis MG, Adler CH, Antelmi E, Arnaldi D, Baldelli L, Boeve BF, Cesari M, Dall’Antonia I, Diederich NJ, Doppler K, Dušek P, Ferri R, Gagnon JF, Gan-Or Z, Hermann W, Högl B, Hu MT, Iranzo A, Janzen A, Kuzkina A, Lee JY, Leenders KL, Lewis SJG, Liguori C, Liu J, Lo C, Ehgoetz Martens KA, Nepozitek J, Plazzi G, Provini F, Puligheddu M, Rolinski M, Rusz J, Stefani A, Summers RLS, Yoo D, Zitser J, Oertel WH (2021) Biomarkers of conversion to α-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder. The Lancet Neurology 20:671–684. https://doi.org/10.1016/s1474-4422(21)00176-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lin CH, Li CH, Yang KC, Lin FJ, Wu CC, Chieh JJ, Chiu MJ (2019) Blood NfL: a biomarker for disease severity and progression in Parkinson disease. Neurology 93:e1104–e1111. https://doi.org/10.1212/wnl.0000000000008088

    Article  CAS  PubMed  Google Scholar 

  5. Ygland Rödström E, Mattsson-Carlgren N, Janelidze S, Hansson O, Puschmann A (2021) Serum Neurofilament light chain as a marker of progression in Parkinson’s disease: long-term observation and implications of clinical subtypes. J Parkinsons Dis. https://doi.org/10.3233/jpd-212866

    Article  Google Scholar 

  6. Aamodt WW, Waligorska T, Shen J, Tropea TF, Siderowf A, Weintraub D, Grossman M, Irwin D, Wolk DA, Xie SX, Trojanowski JQ, Shaw LM, Chen-Plotkin AS (2021) Neurofilament light chain as a biomarker for cognitive decline in Parkinson disease. Mov Disord 36:2945–2950. https://doi.org/10.1002/mds.28779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Niemann L, Lezius S, Maceski A, Leppert D, Englisch C, Schwedhelm E, Zeller T, Gerloff C, Kuhle J, Choe CU (2021) Serum neurofilament is associated with motor function, cognitive decline and subclinical cardiac damage in advanced Parkinson’s disease (MARK-PD). Parkinsonism Relat Disord 90:44–48. https://doi.org/10.1016/j.parkreldis.2021.07.028

    Article  CAS  PubMed  Google Scholar 

  8. Ye R, Locascio JJ, Goodheart AE, Quan M, Zhang B, Gomperts SN (2021) Serum NFL levels predict progression of motor impairment and reduction in putamen dopamine transporter binding ratios in de novo Parkinson’s disease: an 8-year longitudinal study. Parkinsonism Relat Disord 85:11–16. https://doi.org/10.1016/j.parkreldis.2021.02.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mollenhauer B, Dakna M, Kruse N, Galasko D, Foroud T, Zetterberg H, Schade S, Gera RG, Wang W, Gao F, Frasier M, Chahine LM, Coffey CS, Singleton AB, Simuni T, Weintraub D, Seibyl J, Toga AW, Tanner CM, Kieburtz K, Marek K, Siderowf A, Cedarbaum JM, Hutten SJ, Trenkwalder C, Graham D (2020) Validation of serum neurofilament light chain as a biomarker of Parkinson’s disease progression. Mov Disord 35:1999–2008. https://doi.org/10.1002/mds.28206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Park DG, Kim JW, An YS, Chang J, Yoon JH (2021) Plasma neurofilament light chain level and orthostatic hypotension in early Parkinson’s disease. J Neural Transm (Vienna) 128:1853–1861. https://doi.org/10.1007/s00702-021-02423-y

    Article  CAS  PubMed  Google Scholar 

  11. Taki J, Yoshita M, Yamada M, Tonami N (2004) Significance of 123I-MIBG scintigraphy as a pathophysiological indicator in the assessment of Parkinson’s disease and related disorders: it can be a specific marker for Lewy body disease. Ann Nucl Med 18:453–461. https://doi.org/10.1007/bf02984560

    Article  PubMed  Google Scholar 

  12. Orimo S, Yogo M, Nakamura T, Suzuki M, Watanabe H (2016) (123)I-meta-iodobenzylguanidine (MIBG) cardiac scintigraphy in alpha-synucleinopathies. Ageing Res Rev 30:122–133. https://doi.org/10.1016/j.arr.2016.01.001

    Article  CAS  PubMed  Google Scholar 

  13. Horsager J, Andersen KB, Knudsen K, Skjærbæk C, Fedorova TD, Okkels N, Schaeffer E, Bonkat SK, Geday J, Otto M, Sommerauer M, Danielsen EH, Bech E, Kraft J, Munk OL, Hansen SD, Pavese N, Göder R, Brooks DJ, Berg D, Borghammer P (2020) Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study. Brain 143:3077–3088. https://doi.org/10.1093/brain/awaa238

    Article  PubMed  Google Scholar 

  14. Knudsen K, Fedorova TD, Hansen AK, Sommerauer M, Otto M, Svendsen KB, Nahimi A, Stokholm MG, Pavese N, Beier CP, Brooks DJ, Borghammer P (2018) In-vivo staging of pathology in REM sleep behaviour disorder: a multimodality imaging case-control study. Lancet Neurol 17:618–628. https://doi.org/10.1016/s1474-4422(18)30162-5

    Article  PubMed  Google Scholar 

  15. Sakakibara R, Tateno F, Aiba Y, Ogata T, Kishi M, Terada H, Inaoka T, Nakatsuka T, Matsuoka K (2019) MIBG myocardial scintigraphy identifies premotor PD/DLB during a negative DAT scan period: second report. Mov Disord Clin Pract 6:46–50. https://doi.org/10.1002/mdc3.12697

    Article  PubMed  Google Scholar 

  16. Arnulf I (2012) REM sleep behavior disorder: motor manifestations and pathophysiology. Mov Disord 27:677–689. https://doi.org/10.1002/mds.24957

    Article  PubMed  Google Scholar 

  17. Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H (2005) The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695–699. https://doi.org/10.1111/j.1532-5415.2005.53221.x

    Article  PubMed  Google Scholar 

  18. Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Dürr A, Fowler CJ, Kaufmann H, Klockgether T, Lees A, Poewe W, Quinn N, Revesz T, Robertson D, Sandroni P, Seppi K, Vidailhet M (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71:670–676. https://doi.org/10.1212/01.wnl.0000324625.00404.15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH, Deuschl G (2015) MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 30:1591–1601. https://doi.org/10.1002/mds.26424

    Article  PubMed  Google Scholar 

  20. McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D, Aarsland D, Galvin J, Attems J, Ballard CG, Bayston A, Beach TG, Blanc F, Bohnen N, Bonanni L, Bras J, Brundin P, Burn D, Chen-Plotkin A, Duda JE, El-Agnaf O, Feldman H, Ferman TJ, Ffytche D, Fujishiro H, Galasko D, Goldman JG, Gomperts SN, Graff-Radford NR, Honig LS, Iranzo A, Kantarci K, Kaufer D, Kukull W, Lee VMY, Leverenz JB, Lewis S, Lippa C, Lunde A, Masellis M, Masliah E, McLean P, Mollenhauer B, Montine TJ, Moreno E, Mori E, Murray M, O’Brien JT, Orimo S, Postuma RB, Ramaswamy S, Ross OA, Salmon DP, Singleton A, Taylor A, Thomas A, Tiraboschi P, Toledo JB, Trojanowski JQ, Tsuang D, Walker Z, Yamada M, Kosaka K (2017) Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology 89:88–100. https://doi.org/10.1212/wnl.0000000000004058

    Article  PubMed  PubMed Central  Google Scholar 

  21. Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, Goldstein DS, Hainsworth R, Hilz MJ, Jacob G, Kaufmann H, Jordan J, Lipsitz LA, Levine BD, Low PA, Mathias C, Raj SR, Robertson D, Sandroni P, Schatz I, Schondorff R, Stewart JM, van Dijk JG (2011) Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res 21:69–72. https://doi.org/10.1007/s10286-011-0119-5

    Article  PubMed  Google Scholar 

  22. Doty RL, Marcus A, Lee WW (1996) Development of the 12-item cross-cultural smell identification test (CC-SIT). Laryngoscope 106:353–356. https://doi.org/10.1097/00005537-199603000-00021

    Article  CAS  PubMed  Google Scholar 

  23. Bae S, Choi H, Whi W, Paeng JC, Cheon GJ, Kang KW, Lee DS (2020) Spatial normalization using early-phase [(18)F]FP-CIT PET for quantification of striatal dopamine transporter binding. Nucl Med Mol Imaging 54:305–314. https://doi.org/10.1007/s13139-020-00669-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Quadalti C, Calandra-Buonaura G, Baiardi S, Mastrangelo A, Rossi M, Zenesini C, Giannini G, Candelise N, Sambati L, Polischi B, Plazzi G, Capellari S, Cortelli P, Parchi P (2021) Neurofilament light chain and α-synuclein RT-QuIC as differential diagnostic biomarkers in parkinsonisms and related syndromes. NPJ Parkinsons Dis 7:93. https://doi.org/10.1038/s41531-021-00232-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Singer W, Schmeichel AM, Shahnawaz M, Schmelzer JD, Boeve BF, Sletten DM, Gehrking TL, Gehrking JA, Olson AD, Savica R, Suarez MD, Soto C, Low PA (2020) Alpha-synuclein oligomers and neurofilament light chain in spinal fluid differentiate multiple system atrophy from lewy body synucleinopathies. Ann Neurol 88:503–512. https://doi.org/10.1002/ana.25824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Parnetti L, Gaetani L, Di Filippo M (2019) Serum neurofilament light chain as a preclinical marker of neurodegeneration. The Lancet Neurology 18:1070–1071. https://doi.org/10.1016/S1474-4422(19)30405-3

    Article  PubMed  Google Scholar 

  27. Braak H, Rüb U, Del Tredici K (2003) Involvement of precerebellar nuclei in multiple system atrophy. Neuropathol Appl Neurobiol 29:60–76. https://doi.org/10.1046/j.1365-2990.2003.00432.x

    Article  CAS  PubMed  Google Scholar 

  28. Wakabayashi K, Mori F, Nishie M, Oyama Y, Kurihara A, Yoshimoto M, Kuroda N (2005) An autopsy case of early (“minimal change”) olivopontocerebellar atrophy (multiple system atrophy-cerebellar). Acta Neuropathol 110:185–190

    Article  PubMed  Google Scholar 

  29. 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 67:2236–2238. https://doi.org/10.1212/01.wnl.0000249313.25627.2e

    Article  CAS  PubMed  Google Scholar 

  30. Paglionico S, Labate A, Salsone M, Morelli M, Novellino F, Cascini G, Quattrone A (2009) Involvement of cardiac sympathetic nerve endings in a patient with idiopathic RBD and intact nigrostriatal pathway. Parkinsonism Relat Disord 15:789–791. https://doi.org/10.1016/j.parkreldis.2009.03.008

    Article  CAS  PubMed  Google Scholar 

  31. Kashihara K, Imamura T, Shinya T (2010) Cardiac 123I-MIBG uptake is reduced more markedly in patients with REM sleep behavior disorder than in those with early stage Parkinson’s disease. Parkinsonism Relat Disord 16:252–255. https://doi.org/10.1016/j.parkreldis.2009.12.010

    Article  PubMed  Google Scholar 

  32. Gabilondo I, Llorens V, Rodriguez T, Fernández M, Concha TP, Acera M, Tijero B, Murueta-Goyena A, Del Pino R, Cortés J, Gómez-Esteban JC (2019) Myocardial MIBG scintigraphy in genetic Parkinson’s disease as a model for Lewy body disorders. Eur J Nucl Med Mol Imaging 46:376–384. https://doi.org/10.1007/s00259-018-4183-0

    Article  CAS  PubMed  Google Scholar 

  33. Fujishiro H, Iseki E, Murayama N, Yamamoto R, Higashi S, Kasanuki K, Suzuki M, Arai H, Sato K (2010) Diffuse occipital hypometabolism on [18 F]-FDG PET scans in patients with idiopathic REM sleep behavior disorder: prodromal dementia with Lewy bodies? Psychogeriatrics 10:144–152. https://doi.org/10.1111/j.1479-8301.2010.00325.x

    Article  PubMed  Google Scholar 

  34. Barateau L, Jaussent I, Lopez R, Evangelista E, Chenini S, Benkiran M, Mariano-Goulart D, Dauvilliers Y (2018) Cardiac sympathetic activity differentiates idiopathic and symptomatic rapid eye movement sleep behaviour disorder. Sci Rep 8:7304. https://doi.org/10.1038/s41598-018-25547-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Janzen A, Kogan RV, Meles SK, Sittig E, Renken RJ, Geibl FF, Booij J, Stormezand G, Luster M, Mayer G, Leenders KL, Oertel WH (2021) Rapid eye movement sleep behavior disorder: abnormal cardiac image and progressive abnormal metabolic brain pattern. Mov Disord. https://doi.org/10.1002/mds.28859

    Article  PubMed  PubMed Central  Google Scholar 

  36. Park DG, Kang J, An YS, Chang J, Yoon JH (2021) Association of plasma alpha-synuclein with cardiac (123)I-MIBG scintigraphy in early Parkinson’s disease. Neurosci Lett 770:136399. https://doi.org/10.1016/j.neulet.2021.136399

    Article  CAS  PubMed  Google Scholar 

  37. Takahashi M, Ikemura M, Oka T, Uchihara T, Wakabayashi K, Kakita A, Takahashi H, Yoshida M, Toru S, Kobayashi T, Orimo S (2015) Quantitative correlation between cardiac MIBG uptake and remaining axons in the cardiac sympathetic nerve in Lewy body disease. J Neurol Neurosurg Psychiatry 86:939–944. https://doi.org/10.1136/jnnp-2015-310686

    Article  PubMed  Google Scholar 

  38. Ryu DW, Kim JS, Lee JE, Oh YS, Yoo SW, Yoo IR, Lee KS (2019) Initial versus follow-up sequential myocardial 123I-MIBG scintigraphy to discriminate parkinson disease from atypical Parkinsonian syndromes. Clin Nucl Med 44:282–288. https://doi.org/10.1097/RLU.0000000000002424

    Article  PubMed  Google Scholar 

  39. Jennings D, Siderowf A, Stern M, Seibyl J, Eberly S, Oakes D, Marek K (2017) Conversion to parkinson disease in the PARS hyposmic and dopamine transporter-deficit prodromal cohort. JAMA Neurol 74:933–940. https://doi.org/10.1001/jamaneurol.2017.0985

    Article  PubMed  PubMed Central  Google Scholar 

  40. Wang C, Chen F, Li Y, Liu J (2021) Possible predictors of phenoconversion in isolated REM sleep behaviour disorder: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. https://doi.org/10.1136/jnnp-2021-328062

    Article  PubMed  Google Scholar 

  41. Cao M, Li Y, Gu Z, Mi T, Xu X, Ma C, Chen M, Wu M, Chan P (2019) Validation of the utility of the brief smell identification test in Chinese patients with Parkinson’s disease. J Clin Neurosci 60:68–72. https://doi.org/10.1016/j.jocn.2018.10.023

    Article  PubMed  Google Scholar 

  42. Lee JY, Yoon EJ, Kim YK, Shin CW, Nam H, Jeong JM, Kim HJ, Jeon B (2019) Nonmotor and dopamine transporter change in REM sleep behavior disorder by olfactory impairment. J Mov Disord. 12:103–112. https://doi.org/10.14802/jmd.18061

    Article  PubMed  PubMed Central  Google Scholar 

  43. Arnaldi D, Chincarini A, Hu MT, Sonka K, Boeve B, Miyamoto T, Puligheddu M, De Cock VC, Terzaghi M, Plazzi G, Tachibana N, Morbelli S, Rolinski M, Dusek P, Lowe V, Miyamoto M, Figorilli M, Verbizier Dd, Bossert I, Antelmi E, Meli R, Barber TR, Trnka J, Miyagawa T, Serra A, Pizza F, Bauckneht M, Bradley KM, Zogala D, McGowan DR, Jordan L, Manni R, Nobili F (2020) Dopaminergic imaging and clinical predictors for phenoconversion of REM sleep behaviour disorder. Brain 144:278–287. https://doi.org/10.1093/brain/awaa365

    Article  PubMed Central  Google Scholar 

  44. Giannini G, Mastrangelo V, Provini F, Droghini A, Cecere A, Barletta G, Mignani F, Guaraldi P, Cortelli P, Calandra-Buonaura G (2020) Progression and prognosis in multiple system atrophy presenting with REM behavior disorder. Neurology 94:e1828–e1834. https://doi.org/10.1212/wnl.0000000000009372

    Article  PubMed  Google Scholar 

  45. Singer W, Schmeichel AM, Shahnawaz M, Schmelzer JD, Sletten DM, Gehrking TL, Gehrking JA, Olson AD, Suarez MD, Misra PP, Soto C, Low PA (2021) Alpha-synuclein oligomers and neurofilament light Chain predict phenoconversion of pure autonomic failure. Ann Neurol 89:1212–1220. https://doi.org/10.1002/ana.26089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Seo JH, Yong SW, Song SK, Lee JE, Sohn YH, Lee PH (2010) A case-control study of multiple system atrophy in Korean patients. Mov Disord 25:1953–1959. https://doi.org/10.1002/mds.23185

    Article  PubMed  Google Scholar 

  47. Yabe I, Soma H, Takei A, Fujiki N, Yanagihara T, Sasaki H (2006) MSA-C is the predominant clinical phenotype of MSA in Japan: analysis of 142 patients with probable MSA. J Neurol Sci 249:115–121. https://doi.org/10.1016/j.jns.2006.05.064

    Article  PubMed  Google Scholar 

  48. Bugalho P, Salavisa M (2019) Factors influencing the presentation of REM sleep behavior disorder: the relative importance of sex, associated neurological disorder, and context of referral to polysomnography. J Clin Sleep Med 15:1789–1798. https://doi.org/10.5664/jcsm.8086

    Article  PubMed  PubMed Central  Google Scholar 

  49. Fernandez-Arcos A, Iranzo A, Serradell M, Gaig C, Santamaria J (2016) The clinical phenotype of idiopathic rapid eye movement sleep behavior disorder at presentation: a study in 203 consecutive patients. Sleep 39:121–132. https://doi.org/10.5665/sleep.5332

    Article  PubMed  PubMed Central  Google Scholar 

  50. Wing YK, Lam SP, Li SX, Yu MWM, Fong SYY, Tsoh JMY, Ho CKW, Lam VKH (2008) REM sleep behaviour disorder in Hong Kong Chinese: clinical outcome and gender comparison. J Neurol Neurosurg Psychiatry 79:1415–1416. https://doi.org/10.1136/jnnp.2008.155374

    Article  CAS  PubMed  Google Scholar 

  51. Adler CH, Beach TG, Hentz JG, Shill HA, Caviness JN, Driver-Dunckley E, Sabbagh MN, Sue LI, Jacobson SA, Belden CM, Dugger BN (2014) Low clinical diagnostic accuracy of early vs advanced Parkinson disease: clinicopathologic study. Neurology 83:406–412. https://doi.org/10.1212/WNL.0000000000000641

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (No. NRF-2018M3A9E8023859, NRF-2022R1F1A1074588).

Funding

No targeted funding was reported.

Author information

Author notes

  1. Don Gueu Park and Ju Yeong Kim have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Ajou University School of Medicine, 164, Worldcup-Ro, Songjae Hall, Suwon-Si, Gyeonggi-Do, 16499, South Korea

    Don Gueu Park, Mi Hee Kim & Jung Han Yoon

  2. Department of Biomedical Sciences, Ajou University School of Medicine, Suwon-Si, Republic of Korea

    Ju Yeong Kim & Jaerak Chang

  3. Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, South Korea

    Min Seung Kim

  4. Department of Nuclear Medicine, Ajou University School of Medicine, Suwon-Si, Republic of Korea

    Young-Sil An

  5. Department of Brain Science, Ajou University School of Medicine, 164, Worldcup-Ro, Songjae Hall, Suwon-Si, Gyeonggi-Do, 16499, South Korea

    Jaerak Chang

Authors
  1. Don Gueu Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ju Yeong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Min Seung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mi Hee Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Young-Sil An
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jaerak Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jung Han Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

DGP: acquisition and analysis of data; drafting manuscript and figures. JYK: acquisition and analysis of data. MSK: acquisition and analysis of data. MHK: acquisition and analysis of data. Y-SA: acquisition and analysis of data. JC: conception and design of the study; acquisition of data. JHY: conception and design of the study; acquisition and analysis of data; drafting a significant portion of the manuscript.

Corresponding authors

Correspondence to Jaerak Chang or Jung Han Yoon.

Ethics declarations

Conflict of interest

All authors report no disclosures.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board of Ajou University Hospital.

Consent to participate

Written informed consent was obtained from all individual participants included in the study.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 263 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, D.G., Kim, J.Y., Kim, M.S. et al. Neurofilament light chain and cardiac MIBG uptake as predictors for phenoconversion in isolated REM sleep behavior disorder. J Neurol 270, 4393–4402 (2023). https://doi.org/10.1007/s00415-023-11785-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-023-11785-0

Keywords

Search

Navigation