Vol.19 No FTD 3 Pick 2 3 frontal lobe degeneration: FLDPick Pick FLD MND FLD 図 1 3) Frontotemporal lobar degeneration(ftld) 概念の台頭と定着 FTD progre

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1 Frontotemporal lobar degeneration 変遷する病理学的概念と定型的臨床徴候 Frontotemporal lobar degeneration: ever evolving pathological concepts and typical clinical presentations 昭和大学横浜市北部病院内科 / 准教授 ( 神経内科担当 ) * はじめに Frontotemporal lobar degeneration FTLD frontotemporal dementia FTD progressive nonfluent aphasia PNFA semantic dementia SD 3 PNFA progressive aphemia FTD PPA FTLD 1) Pick 病の歴史 1892 Arnold Pick Alois Alzheimer 1911 Pick Onari Spatz Pick Pick Constantinidis Pick Pick B Pick Pick A Pick C Pick C Pick Pick Pick Pick 2) Frontotemporal dementia(ftd) 概念の台頭と変遷 1980 Neary ADdementia of frontal lobe type DFT frontal lobe dementia FLD DFT/FLD Pick 1994 FTD frontotemporal dementia FTD a) b) c) FTD * Toshiya Fukui, Associate professor: Showa University Northern Yokohama Hospital, Internal Medicine (Neurology)

2 Vol.19 No FTD 3 Pick 2 3 frontal lobe degeneration: FLDPick Pick FLD MND FLD 図 1 3) Frontotemporal lobar degeneration(ftld) 概念の台頭と定着 FTD progressive aphasia: PA semantic dementia: SD FTD 1996 frontotemporal lobar degeneration FTLD FTLD AD FTD PA SD FTD 1998 FTLD PA progressive nonfluent aphasia PNFA FTLD FTD PNFA SD 3 FTLD 1992 図 2 4) 免疫組織学的分類の発展 FLD Basophilic Inclusion Body Disease: BIBD intermediate filament neuronal intermediate filament inclusion disease: NIFID RNA TAR (transactive response)-dna binding protein 43 TDP FTLD Pick AD tauopathy tau-positive FTLD FTLD FTLD-U BIBD NIFID Dementia Lacking Distinctive Histology DLDH FTLD-U TDP-43 UPS 2009 FTLD-UPS FTLD-U FTLD-UPS FTLD-IF BIBD ALS 16 fused in sarcoma/translated in liposarcoma FUS/TLS 2010 FTLD-FUS FTDL-UPS CHMP2B 3 FTD FTD-3 Tau-positive FTLD FTLD-tau FTLD FTLD-tau -TDP -UPS -FUS -ni no inclusions 5 FTLD-tau -TDP -FUS 図 3 FTLD 図 4 前頭側頭型認知症 (FTD) 概念前頭側頭葉に限局性萎縮中心を有し, 人格行動感情障害を呈する変性疾患前頭側頭葉変性症 (FTLD) 概念前頭葉側頭葉に限局性萎縮を呈する変性疾患前頭側頭型認知症 (FTD) 運動ニューロン疾患を伴った前頭側頭型認知症 Frontal lobe degeneration (FLD) type Pick type FLD に運動ニューロン疾患 (MND) を伴う FLD/MND type 前頭側頭型認知症 FTD 進行性非流暢性失語 PNFA 意味性認知症 SD FLD type Pick type FLD/MND type 図 FTD 図 FTLD

3 Frontotemporal lobar degeneration 2007 年における考え方 :Cairns NJ et al tau-positive FTLD TDP-43(+) FTLD-U NIFID TDP-43(-) BIBD DLDH 前頭側頭葉変性症 (FTLD) 概念前頭葉側頭葉に限局性萎縮を呈する変性疾患 2009 年における考え方 :Mackenzie et al FTLD-tau FTLD-TDP FTLD-UPS FTLD-IF 2010 年における考え方 :Mackenzie et al FTLD-tau FTLD-TDP FTLD-UPS (FTD-3) 図 3 FTLD ) 最新の FTD 診断基準と PPA 分類 FTLD-FUS BIBD FTLD-U: frontotemporal lobar degeneration with ubiquitinated inclusions NIFID: neuronal intermediate filament inclusion disease BIBD: basophilic inclusions body disease DLDH: dementia lacking distinctive histology FTLD-UPS: FTLD with inclusions detectable with immunohistochemistry against proteins of the ubiquitin proteasome system (UPS) IF: intermediate filaments NI: no inclusions FTLD-ni FTLD-ni FTD 表 PPA 図 5 FTLD PNFA SD logopenic/phonological variant PPA FTD SD PNFA 前頭側頭型認知症 FTD 進行性非流暢性失語 PNFA 意味性認知症 SD FTLD-tau FTLD-TDP FTLD-UPS FTLD-FUS FTLD-ni 図 4 FTLD 表 1 FTD (behavioural variant FTD) I. 変性疾患であること II. Possible bv FTD (3 項目 ) A. 脱抑制 B. アパシー / 無気力 C. 同情 / 感情移入欠如 D. 保続的 / 紋切型 / 強迫的 / 儀式的行動 E. 口唇傾向 / 食行動変化 F. 実行機能障害 ( 記憶 / 視空間認知は比較的保たれる ) IV. FTLD の確定的病理所見を有する bvftd possible/probable bvftd であり FTLD の組織病理所見を有するまたは FTLD の遺伝子変異を有する Nonfluent/Agrammatic 非流暢性下前頭溝 ~ 中前頭回後部失文法下前頭回 ~ 縁上回 Semantic 意味障害側頭極 Logopenic 復唱障害上側頭回後部図 5 inferior frontal sulcus III. Probable bvftd possible bvftd を満たす ADL 機能の明らかな低下前頭葉 / 前部側頭葉の萎縮 / 血流低下 / 代謝低下 posterior middle frontal gyrus anterior temporal V. 除外項目他疾患精神疾患 AD のバイオマーカー陽性 Rascovsky K et al. Brain 2011;134: sensory motor cortex inferior frontal gyrus supramarginal gyrus superior temporal gyrus reduced cortical thickness Rogalski E et al. J Neurosci. 2011;31: primary progressive aphasia まとめ FTLD 3 FTD PNFA SD 3 FTDL-tau FTLD-TDP FTLD-FUS FTLD bv FTD PPA 文献 1 Pick A. Über die Beziehungen der senilen Hirnatrophie zur Aphasie. Prag. Med. Wochenschr. 1892;17: Onari K, Spatz H. Anatomische Beiträge zur Lehre von der Pickschen umschriebenen Großhirnrinden- Atrophie ( Picksche Krankheit ). Z. Gesamte. Neurol. Psychiatr. 1926;101: Constantinidis J, Richard J, Tissot R. Pick's disease. Histological and clinical correlations. Eur Neurol

4 Vol.19 No ;11(4): Gibb WR, Luthert PJ, Marsden CD. Corticobasal degeneration. Brain 1989;112: Pick 1999;50: Neary D, Snowden JS, Northen B, Goulding P. Dementia of frontal lobe type. J Neurol Neurosurg Psychiatry. 1988;51: Neary D, Snowden JS, Mann DM, Northen B, Goulding PJ, Macdermott N. Frontal lobe dementia and motor neuron disease. J Neurol Neurosurg Psychiatry. 1990;53: Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups. J Neurol Neurosurg Psychiatry. 1994;57: Snowden JS, Neary D, Mann DM, Goulding PJ, Testa HJ. Progressive language disorder due to lobar atrophy. Ann Neurol. 1992;31: Neary D, Snowden JS, Mann DMA. Familial progressive aphasia: its relationship to other forms of lobar atrophy. J Neurol Neurosurg Psychiatry. 1993;56: Hodges JR, Patterson K, Oxbury S, Funnell E. Semantic dementia. Progressive fluent aphasia with temporal lobe atrophy. Brain. 1992;115: Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert PH, Albert M, Boone K, Miller BL, Cummings J, Benson DF. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998;51: Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H, Mann D, Tsuchiya K, Yoshida M, Hashizume Y, Oda T. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun. 2006;351: Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006;314: Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ, White CL 3rd, Schneider JA, Grinberg LT, Halliday G, Duyckaerts C, Lowe JS, Holm IE, Tolnay M, Okamoto K, Yokoo H, Murayama S, Woulfe J, Munoz DG, Dickson DW, Ince PG, Trojanowski JQ, Mann DM. Consortium for Frontotemporal Lobar Degeneration. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol. 2007;114: Mackenzie IR, Neumann M, Bigio EH, Cairns NJ, Alafuzoff I, Kril J, Kovacs GG, Ghetti B, Halliday G, Holm IE, Ince PG, Kamphorst W, Revesz T, Rozemuller AJ, Kumar-Singh S, Akiyama H, Baborie A, Spina S, Dickson DW, Trojanowski JQ, Mann DM. Nomenclature for neuropathologic subtypes of frontotemporal lobar degeneration: consensus recommendations. Acta Neuropathol. 2009;117: Mackenzie IR, Neumann M, Bigio EH, Cairns NJ, Alafuzoff I, Kril J, Kovacs GG, Ghetti B, Halliday G, Holm IE, Ince PG, Kamphorst W, Revesz T, Rozemuller AJ, Kumar-Singh S, Akiyama H, Baborie A, Spina S, Dickson DW, Trojanowski JQ, Mann DM. Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update. Acta Neuropathol. 2010;119: Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC, Seelaar H, Dopper EG, Onyike CU, Hillis AE, Josephs KA, Boeve BF, Kertesz A, Seeley WW, Rankin KP, Johnson JK, Gorno-Tempini ML, Rosen H, Prioleau-Latham CE, Lee A, Kipps CM, Lillo P, Piguet O, Rohrer JD, Rossor MN, Warren JD, Fox NC, Galasko D, Salmon DP, Black SE, Mesulam M, Weintraub S, Dickerson BC, Diehl-Schmid J, Pasquier F, Deramecourt V, Lebert F, Pijnenburg Y, Chow TW, Manes F, Grafman J, Cappa SF, Freedman M, Grossman M, Miller BL. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134: Gorno-Tempini ML, Hillis AE, Weintraub S,

5 Frontotemporal lobar degeneration Kertesz A, Mendez M, Cappa SF, Ogar JM, Rohrer JD, Black S, Boeve BF, Manes F, Dronkers NF, Vandenberghe R, Rascovsky K, Patterson K, Miller BL, Knopman DS, Hodges JR, Mesulam MM, Grossman M. Classification of primary progressive aphasia and its variants. Neurology. 2011;76: Gorno-Tempini ML, Brambati SM, Ginex V, Ogar J, Dronkers NF, Marcone A, Perani D, Garibotto V, Cappa SF, Miller BL. The logopenic/phonological variant of primary progressive aphasia. Neurology Oct 14;71(16):

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untitled Ⅷ 184 Ⅰ 定義, 概要, 経過, 疫学 Ⅱ 診断 Ⅲ 治療原則, 選択肢 Ⅳ 経過, 治療計画 ⅤAD Ⅵ VaD CQ Ⅷ-1 frontotemporal dementia(ftd) と前頭側頭葉変性症 frontotemporal lobar degeneration(ftld) との相違点は推奨 FTD と FTLD はしばしば同義語として使用される場合があるが, FTD は FTLD