BRAIN and NERVE－神経研究の進歩72巻2号

2020年02月発行

特集 αシヌクレイノパチーの新たな展開

疾患修飾療法の成功を目指した多系統萎縮症の診断

著者： 下畑享良¹

所属機関： ¹岐阜大学大学院医学系研究科脳神経内科学分野

ページ範囲：P.131 - P.136

文献概要

疾患修飾療法の成功のためには，より正確で早期の診断が必要である。しかし多系統萎縮症（MSA）では，多様な臨床表現型を呈すること，mimicsと呼ばれるMSAに類似した表現型を呈する疾患が多数存在することから，その臨床診断は容易ではない。本論では臨床診断を困難にしているこれらの要因について提示し，最近の臨床試験の状況を踏まえた新たな診断基準作成に向けての動きを紹介したい。

参考文献

1)Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, et al: Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71: 670-676, 2008

2)Ceponiene R, Edland SD, Reid TN, Al Rizaiza A, Litvan I: Neuropsychiatric symptoms and their impact on quality of life in multiple system atrophy. Cogent Psychology 3: 1131476, 2016［doi: 10.1080/23311908.2015.1131476］

3)Sakushima K, Nishimoto N, Nojima M, Matsushima M, Yabe I, et al: Epidemiology of Multiple System Atrophy in Hokkaido, the Northernmost Island of Japan. Cerebellum 14: 682-687, 2015

4)Multiple-System Atrophy Research Collaboration: Mutations in COQ2 in familial and sporadic multiple-system atrophy. N Engl J Med 369: 233-244, 2013

5)Stankovic I, Krismer F, Jesic A, Antonini A, Benke T, et al: Cognitive impairment in multiple system atrophy: a position statement by the Neuropsychology Task Force of the MDS Multiple System Atrophy (MODIMSA) study group. Mov Disord 29: 857-867, 2014

6)Umoto M, Miwa H, Ando R, Kajimoto Y, Kondo T: White matter hyperintensities in patients with multiple system atrophy. Parkinsonism Relat Disord 18: 17-20, 2012

7)Höglinger GU, Respondek G, Stamelou M, Kurz C, Josephs KA, et al: Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Mov Disord 32: 853-864, 2017

8)Abele M, Minnerop M, Urbach H, Specht K, Klockgether T: Sporadic adult onset ataxia of unknown etiology: a clinical, electrophysiological and imaging study. J Neurol 254: 1384-1389, 2007

9)Yoshida K, Kuwabara S, Nakamura K, Abe R, Matsushima A, et al: Idiopathic cerebellar ataxia (IDCA): diagnostic criteria and clinical analyses of 63 Japanese patients. J Neurol Sci 384: 30-35, 2018

10)Riku Y, Watanabe H, Mimuro M, Iwasaki Y, Ito M, et al: Non-motor multiple system atrophy associated with sudden death: Pathological observations of autonomic nuclei. J Neurol 264: 2249-2257, 2017

11)Aoki N, Boyer PJ, Lund C, Lin WL, Koga S, et al: Atypical multiple system atrophy is a new subtype of frontotemporal lobar degeneration: frontotemporal lobar degeneration associated with α-synuclein. Acta Neuropathol 130: 93-105, 2015

12)Batla A, De Pablo-Fernandez E, Erro R, Reich M, Calandra-Buonaura G, et al: Young-onset multiple system atrophy: clinical and pathological features. Mov Disord 33: 1099-1107, 2018

13)Stankovic I, Krismer F, Jesic A, Antonini A, Benke T, et al: Cognitive impairment in multiple system atrophy: a position statement by the Neuropsychology Task Force of the MDS Multiple System Atrophy (MODIMSA) study group. Mov Disord 29: 857-867, 2014

14)Osaki Y, Wenning GK, Daniel SE, Hughes A, Lees AJ, et al: Do published criteria improve clinical diagnostic accuracy in multiple system atrophy? Neurology 59: 1486-1491, 2002

15)Joutsa J, Gardberg M, Röyttä M, Kaasinen V: Diagnostic accuracy of parkinsonism syndromes by general neurologists. Parkinsonism Relat Disord 20: 840-844, 2014

16)Koga S, Aoki N, Uitti RJ, van Gerpen JA, Cheshire WP, et al: When DLB, PD, and PSP masquerade as MSA: an autopsy study of 134 patients. Neurology 85: 404-412, 2015

17)McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, et al: Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology 89: 88-100, 2017

18)Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, et al: MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord 30: 1591-1601, 2015

19)Anderson T, Luxon L, Quinn N, Daniel S, David Marsden C, et al: Oculomotor function in multiple system atrophy: clinical and laboratory features in 30 patients. Mov Disord 23: 977-984, 2008

20)Shimohata T, Kanazawa M, Yoshida M, Saito Y, Iwai K, et al: Clinical and imaging findings of progressive supranuclear palsy with predominant cerebellar ataxia. Mov Disord 31: 760-762, 2016

21)Kouri N, Oshima K, Takahashi M, Murray ME, Ahmed Z, et al: Corticobasal degeneration with olivopontocerebellar atrophy and TDP-43 pathology: an unusual clinicopathologic variant of CBD. Acta Neuropathol 125: 741-752, 2013

22)Lee YC, Liu CS, Wu HM, Wang PS, Chang MH, et al: The ‘hot cross bun’ sign in the patients with spinocerebellar ataxia. Eur J Neurol 16: 513-516, 2009

23)Soares-Fernandes JP, Ribeiro M, Machado A: “Hot cross bun” sign in variant Creutzfeldt-Jakob disease. AJNR Am J Neuroradiol 30: E37, 2009［doi: 10.3174/ajnr.A1335］

24)Roh SY, Jang HS, Kim YH. Hot cross bun sign following bilateral pontine infarction: a case report. J Mov Disord 6: 37-39, 2013

25)Loy CT, Sweeney MG, Davis MB, Wills AJ, Sawle GV, et al: Spinocerebellar ataxia type 17: extension of phenotype with putaminal rim hyperintensity on magnetic resonance imaging. Mov Disord 20: 1521-1523, 2005

26)Schneider SA, Marshall KE, Xiao J, LeDoux MS: JPH3 repeat expansions cause a progressive akinetic-rigid syndrome with severe dementia and putaminal rim in a five-generation African-American family. Neurogenetics 13: 133-140, 2012

27)Dodel R, Spottke A, Gerhard A, Reuss A, Reinecker S, et al: Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [(11)C](R)-PK11195 PET (MEMSA-trial). Mov Disord 25; 97-107, 2010

28)Hall S, Öhrfelt A, Constantinescu R, Andreasson U, Surova Y, et al: Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and/or parkinsonian disorders. Arch Neurol 69: 1445-1452, 2012

29)Magdalinou NK, Paterson RW, Schott JM, Fox NC, Mummery C, et al: A panel of nine cerebrospinal fluid biomarkers may identify patients with atypical parkinsonian syndromes. J Neurol Neurosurg Psychiatry 86: 1240-1247, 2015

30)Hansson O, Janelidze S, Hall S, Magdalinou N, Lees AJ, et al: Blood-based NfL: a biomarker for differential diagnosis of parkinsonian disorder. Neurology 88: 930-937, 2017

31)Olsson B, Portelius E, Cullen NC, Sandelius Å, Zetterberg H, et al: Association of Cerebrospinal Fluid Neurofilament Light Protein Levels With Cognition in Patients With Dementia, Motor Neuron Disease, and Movement Disorders. JAMA Neurol 76: 318-325, 2019

32)Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, et al: Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol 14: 577-589, 2018

33)Nomura T, Inoue Y, Högl B, Uemura Y, Yasui K, et al: Comparison of the clinical features of rapid eye movement sleep behavior disorder in patients with Parkinson's disease and multiple system atrophy. Psychiatry Clin Neurosci 65: 264-271, 2011

34)下畑享良, 井上雄一, 平田幸一: Rapid eye movement（REM）睡眠行動障害の診断, 告知, 治療. 臨床神経57: 63-70, 2017

35)Tolosa E, Vilas D: Peripheral synuclein tissue markers: a step closer to Parkinson's disease diagnosis. Brain 138: 2120-2122, 2015

36)Zange L, Noack C, Hahn K, Stenzel W, Lipp A: Phosphorylated α-synuclein in skin nerve fibres differentiates Parkinson's disease from multiple system atrophy. Brain 138: 2310-2321, 2015

37)Levin J, Maaß S, Schuberth M, Giese A, Oertel WH, et al: Safety and efficacy of epigallocatechin gallate in multiple system atrophy (PROMESA): a randomised, double-blind, placebo-controlled trial. Lancet Neurol 18: 724-735, 2019

38)Stankovic I, Quinn N, Vignatelli L, Antonini A, Berg D, et al: A critique of the second consensus criteria for multiple system atrophy. Mov Disord 34: 975-984, 2019

39)Walsh RR, Krismer F, Galpern WR, Wenning GK, Low PA, et al: Recommendations of the Global Multiple System Atrophy Research Roadmap Meeting. Neurology 90: 74-82, 2018