BRAIN and NERVE－神経研究の進歩70巻1号

2018年01月発行

特集 筋痛性脳脊髄炎／慢性疲労症候群の今

筋痛性脳脊髄炎／慢性疲労症候群と脳内神経炎症

著者： 中富康仁¹² 倉恒弘彦²³⁴ 渡辺恭良⁵⁶⁷

所属機関： ¹ナカトミファティーグケアクリニック ²大阪市立大学医学部附属病院疲労クリニカルセンター ³関西福祉科学大学健康福祉学部 ⁴大阪市立大学大学院医学研究科代謝内分泌病態内科学 ⁵理化学研究所ライフサイエンス技術基盤研究センター ⁶理化学研究所健康“生き活き”羅針盤リサーチコンプレックス推進プログラム ⁷大阪市立大学健康科学イノベーションセンター

ページ範囲：P.19 - P.25

文献概要

筋痛性脳脊髄炎／慢性疲労症候群（ME/CFS）は，慢性で深刻な原因不明の疲労，認知機能障害や，慢性的で広範な疼痛を特徴とする疾患である。われわれは世界で初めてME/CFS患者における脳内神経炎症をポジトロンエミッション断層撮影（PET）によって明らかにした。神経炎症は患者の広範な脳領域に存在し，神経心理学的症状の重症度と関連していた。現在，診断法および治療の開発につなげる研究がスタートしている。

参考文献

1)Afari N, Buchwald D: Chronic fatigue syndrome: a review. Am J Psychiatry 160: 221-236, 2003

2)Kuratsune H, Yamaguti K, Lindh G, Evengård B, Hagberg G, et al: Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain. NeuroImage 17: 1256-1265, 2002

3)Yamamoto S, Ouchi Y, Onoe H, Yoshikawa E, Tsukada H, et al: Reduction of serotonin transporters of patients with chronic fatigue syndrome. Neuroreport 15: 2571-2574, 2004

4)Okada T, Tanaka M, Kuratsune H, Watanabe Y, Sadato N: Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome. BMC Neurol 4: 14, 2004［doi: 10.1186/1471-2377-4-14］

5)Chaudhuri A, Behan PO: Fatigue in neurological disorders. Lancet 363: 978-988, 2004

6)Pavese N, Metta V, Bose SK, Chaudhuri KR, Brooks DJ: Fatigue in Parkinson's disease is linked to striatal and limbic serotonergic dysfunction. Brain 133: 3434-3443, 2010

7)Chen MK, Guilarte TR: Translocator protein 18 kDa (TSPO): molecular sensor of brain injury and repair. Pharmacol Ther 118: 1-17, 2008

8)Natelson BH, Haghighi MH, Ponzio NM: Evidence for the presence of immune dysfunction in chronic fatigue syndrome. Clin Diagn Lab Immunol 9: 747-752, 2002

9)Natelson BH, Weaver SA, Tseng CL, Ottenweller JE: Spinal fluid abnormalities in patients with chronic fatigue syndrome. Clin Diagn Lab Immunol 12: 52-55, 2005

10)Morris G, Maes M: A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome. Metab Brain Dis 28: 523-540, 2013

11)Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, et al: An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab 32: 1-5, 2012

C-(R)-PK11195 PET study. J Nucl Med 55:945-950, 2014

13)Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, et al: The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 121: 953-959, 1994

14)Carruthers BM, van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, et al: Myalgic encephalomyelitis: International Consensus Criteria. J Intern Med 270: 327-338, 2011

15)Lee KA, Hicks G, Nino-Murcia G: Validity and reliability of a scale to assess fatigue. Psychiatry Res 36: 291-298, 1991

16)Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, et al: Development of a fatigue scale. J Psychosom Res 37: 147-153, 1993

17)Radloff LS: The CES-D Scale; A self-report depression scale for research in the general population. Appl Psychol Meas 1: 385-401, 1977

18)de Lange FP, Kalkman JS, Bleijenberg G, Hagoort P, van der Werf SP, et al: Neural correlates of the chronic fatigue syndrome--an fMRI study. Brain 127: 1948-1957, 2004

19)Lipton P: Ischemic cell death in brain neurons. Physiol Rev 79: 1431-1568, 1999

20)Pall ML: Elevated, sustained peroxynitrite levels as the cause of chronic fatigue syndrome. Med Hypotheses 54: 115-125, 2000

21)Basu S: F2-isoprostanes in human health and diseases: from molecular mechanisms to clinical implications. Antioxid Redox Signal 10: 1405-1434, 2008

22)Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, et al: In-vivo measurement of activated microglia in dementia. Lancet 358: 461-467, 2001

23)Yokokura M, Mori N, Yagi S, Yoshikawa E, Kikuchi M, et al: In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer's disease. Eur J Nucl Med Mol Imaging 38: 343-351, 2011

24)Van der Werf YD, Witter MP, Groenewegen HJ: The intralaminar and midline nuclei of the thalamus. Anatomical and functional evidence for participation in processes of arousal and awareness. Brain Res Brain Res Rev 39: 107-140, 2002

25)Morriss RK, Robson MJ, Deakin JF: Neuropsychological performance and noradrenaline function in chronic fatigue syndrome under conditions of high arousal. Psychopharmacology (Berl) 163: 166-173, 2002

26)Phelps EA, LeDoux JE: Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron 48: 175-187, 2005

27)Gupta A: Unconscious amygdalar fear conditioning in a subset of chronic fatigue syndrome patients. Med Hypotheses 59: 727-735, 2002

28)Van Houdenhove B, Kempke S, Luyten P: Psychiatric aspects of chronic fatigue syndrome and fibromyalgia. Curr Psychiatry Rep 12: 208-214, 2010

29)Farooq RK, Isingrini E, Tanti A, Le Guisquet AM, Arlicot N, et al: Is unpredictable chronic mild stress (UCMS) a reliable model to study depression-induced neuroinflammation? Behav Brain Res 231: 130-137, 2012

30)Ekdahl CT, Kokaia Z, Lindvall O: Brain inflammation and adult neurogenesis: the dual role of microglia. Neuroscience 158: 1021-1029, 2009

31)Harte SE, Spuz CA, Borszcz GS: Functional interaction between medial thalamus and rostral anterior cingulate cortex in the suppression of pain affect. Neuroscience 172: 460-473, 2011

32)倉恒弘彦: 線維筋痛症をモデルとした慢性疼痛機序の解明と治療法の確立に関する研究—線維筋痛症患者におけるミクログリアの活性化（神経炎症）. 厚生労働科学研究委託費慢性の痛み解明研究事業. 線維筋痛症の病因・病態の解明と客観的診断・評価法の開発及びトータルマネジメントの確立に関する戦略的総合研究. 平成26年度委託業務成果報告書（代表研究者: 松本美冨士）. 2015, pp14-17