今日の臨床サポート

進行性核上性麻痺

著者: 渡辺宏久 藤田医科大学医学部 脳神経内科学教室

監修: 高橋裕秀 昭和大学藤が丘病院 脳神経内科

著者校正/監修レビュー済:2021/10/13
参考ガイドライン:
  1. 日本神経学会:認知症疾患診療ガイドライン2017
患者向け説明資料

概要・推奨   

  1. 典型的な進行性核上性麻痺(Richardson症候群、PSP-RS)を理解する必要がある(推奨度1)。
  1. 進行性核上性麻痺(PSP)の臨床像は多彩で、パーキンソン病と非常に類似した臨床像を呈する場合もある。初期にパーキンソン病と診断した症例でも診断の定期的な見直しが勧められる(推奨度1)。
  1. 2017年に新しい診断基準MDS PSP diagnostic criteriaが提唱された(推奨度1)。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧に
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧に
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
渡辺宏久 : 特に申告事項無し[2021年]
監修:高橋裕秀 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行った(変更なし)。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 進行性核上性麻痺(PSP)は1964年に小規模な症例集積研究に基づいて、垂直性核上性注視麻痺を主徴とし、主に脳幹の神経細胞変性を特徴とする、成人発症で比較的急速に進行する神経変性疾患として記載された。
  1. PSPの診断には、垂直性核上性眼球運動障害の存在と発症後1年以内の転倒を伴う姿勢の不安定性が重要とされた。幅広く用いられてきたNINDS-SPSPの診断基準:<図表>を示す。
  1. 一方、NINDS-SPSPの診断基準は、特異度は非常に高いが、初診時の感度が低いことが問題であった。また、剖検で確定されたPSPの患者において非定型のPSPの臨床症状を示す症例の多いことが明らかとなった。これらを踏まえ、2017年に新しい診断基準MDS PSP diagnostic criteriaが提唱された[1]
 
基本的特徴

出典

img1:  Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria.
 
 Mov Disord. 2017 Jun;32(6):853-864. doi:・・・
 
  1. MDS診断基準では、基本的特徴、中核となる特徴、支持的特徴、操作的定義、確実性のレベルを理解する。
  1. 基本的特徴は必須の適格基準(孤発性、初発年齢が40歳以上、緩徐な進行)、必須の除外基準、状況依存性除外基準の3項目から構成されている<図表>。MAPT遺伝子のレアバリアントは遺伝性、早期発症を示しうることに留意する。
  1. 中核となる特徴の4つのドメインは、眼球運動機能異常、姿勢保持障害、運動緩慢、認知機能障害であり、それぞれPSPの診断の確実性に寄与するレベルを3段階に分けて特徴が記載されている。
 
中核となる臨床的特徴

レベルの数字が小さいほど、数字が大きいものより、PSPの診断におけるより高い確実性に寄与すると考えられる。中核となる臨床的特徴の操作的定義は<図表>を参照。

出典

img1:  Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria.
 
 Mov Disord. 2017 Jun;32(6):853-864. doi:・・・
 
  1. 支持的特徴には、臨床的手掛かりとして、①レボドパ抵抗性、②運動減少性・痙性構音障害、③嚥下障害、④羞明、画像所見として、①顕著な中脳萎縮ないし低代謝、2)シナプス後線条体ドパミン神経変性が含まれる。
 
支持的特徴

出典

img1:  Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria.
 
 Mov Disord. 2017 Jun;32(6):853-864. doi:・・・
 
  1. 操作的定義では4種類のドメイン毎に診断を支持するレベルに応じて3段階の臨床的特徴ならびにその定義を記載してある<図表>。最も診断を支持する特徴は、ドメイン毎に、垂直性核上性注視麻痺(O1)、3年以内に繰り返す誘発によらない転倒(P1)、3年以内の進行性すくみ足(A1)、発語・言語障害(非流暢性/失文法性の原発性進行性失語症、発語失行など)(C1)である。次に診断を支持する特徴は、同じくドメイン毎に、緩徐な垂直衝動性運動(O2)、3年以内のpull testにおける転倒(P2)、レボドパ抵抗性で、運動緩慢と筋強剛主体で、体軸優位のパーキンソン症状(A2)、前頭葉性の認知・行動障害(①アパシー、②精神緩慢、③遂行機能障害症候群、④音素性語彙流暢性の低下、⑤衝動性、脱抑制、または保続の5つの中で3つ以上)(C2)である。
 
中核となる臨床的特徴、支持的な臨床的手掛かり、および支持的な画像所見の操作的定義

出典

img1:  Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria.
 
 Mov Disord. 2017 Jun;32(6):853-864. doi:・・・
 
  1. 病理所見からdefinite(確実)、基本的特徴、12種類の臨床的特徴、6種類の支持的特徴の組み合わせからprobable(ほぼ確実)、possible(疑い)、suggestive(示唆)の4段階の診断の確実性が定義される。
 
臨床的特徴および臨床的手掛かりの組み合わせにより得られる診断の確実性の程度

出典

img1:  Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria.
 
 Mov Disord. 2017 Jun;32(6):853-864. doi:・・・
 
  1. Definite PSPは、神経病理診断例で、臨床症状を問わない。病理学的にPSPはアルツハイマー病、大脳皮質基底核変性症、ピック病などとともにタウオパチーに分類される。
  1. Probable PSPは、特異度は高いが感度はそれほど高くないとされる。いずれも垂直性核上性注視麻痺(O1)もしくは、緩徐な垂直衝動性運動(O2)が必須で、①Richardson症候群(PSP-RS)((O1またはO2)+(P1またはP2))、②パーキンソニズムを主徴とするPSP(PSP-P)((O1またはO2)+(A2またはA3))、③進行性すくみ足を伴うPSP(PSP-PFG)((O1またはO2)+A1)と④前頭葉徴候を主徴とするPSP(PSP-F)((O1またはO2)+C2)の4病型が含まれる。
  1. Possible PSPは、感度は十分に高いが特異度は低いとされる。①垂直性核上性注視麻痺(O1)を呈するPSP-OM、②緩徐な垂直衝動性運動(O2)と3年以内のpull testにおける転倒傾向(P3)を認めるRichardson症候群(PSP-RS)、③3年以内に繰り返す誘発によらない転倒(P1)もしくは3年以内のpull testにおける転倒(P2)を認める進行性すくみ足を伴う PSP(PSP-PGF)、④発語・言語障害の臨床像(C1)に垂直性核上性注視麻痺(O1)もしくは、緩徐な垂直衝動性運動(O2)を認める発語・言語障害を主徴とするPSP(PSP-SL)、⑤大脳皮質基底核症候群の臨床像(C3)に垂直性核上性注視麻痺(O1)もしくは、緩徐な垂直衝動性運動(O2)を認める大脳皮質基底核症候群を主徴とするPSP(PSP-CBS)が含まれる。
  1. Suggestive of PSPは、PSPが示唆されるが、possible またはprobable PSPの条件を満たさないとされる。①3年以内に繰り返す誘発によらない転倒(P1)または3年以内のpull testにおける転倒(P2)を主徴とする姿勢保持障害を主体とするPSP-PI、②頻回の粗大矩形眼球運動もしくは開眼失行(O3)に3年以内のpull testにおける転倒(P2)もしくは3年以内のpull testにおける3歩以上の後退(P3)を主体とするPSP-RS、③レボドパ抵抗性で、運動緩慢と筋強剛主体で、体軸優位のパーキンソン症状(A2)もしくはパーキンソン病として典型的なパーキンソン症状(A3)にパーキンソン病よりもPSPを考えやすい臨床特徴(頻回の粗大矩形眼球運動もしくは開眼失行(O3)、3年以内に繰り返す誘発によらない転倒(P1)または3年以内のpull testにおける転倒(P2)、発語・言語障害(非流暢性/失文法性の原発性進行性失語症、発語失行など)(C1)、前頭葉性の認知・行動障害(5つ中3つ以上)(C2)、レボドパ抵抗性(CC1)、運動減少性・痙性構音障害(CC2)、嚥下障害(CC3)、羞明(CC4)のいずれか)を認めるパーキンソニズムを主徴とするPSP-P、④発語・言語障害(非流暢性/失文法性の原発性進行性失語症、発語失行など)(C1)を認め、発語・言語小体を主徴とするPSP-CL、⑤前頭葉性の認知・行動障害(5つ中3つ以上)(C2)に頻回の粗大矩形眼球運動もしくは開眼失行(O3)もしくは3年以内のpull testにおける転倒傾向(P3)を認める前頭葉徴候を主徴とするPSP-F、⑥大脳皮質基底核症候群(C3)を主徴とするPSP-CBSが含まれる。
  1. 臨床病型は、ある時期に複数の病型を満たす場合や進行に応じて変化する可能性がある。
  1. 複数の病型を満たす場合には、①診断の確実性のレベルの高い病型を優先、②同等であれば病型診断した時期が早い病型を優先、③いずれも同等であれば病型の序列(PSP-RS>PSP-OM>PSP-PI>その他)で決定する[2]
  1. アルゴリズムに診断の流れ、<図表>に診断基準のまとめを記した。
 
MDS PSP 診断基準の流れ

出典

img1:  
 
 
 
MDS PSP 診断基準のまとめ

出典

img1:  
 
 
 
  1. MDSの基準を用いても、感度はprobable 47.0%、possible 51.5%、suggestive 87.9%とsuggestiveでなければ十分高くならない。一方、特異度はprobable 85.7%、possible 84.1%、suggestive 39.7%と、suggestiveはかなり低い。また発症から3年以内の早期診断は難しいことも留意すべきである[3]
 
PSPの臨床病型

病理学的にPSPである症例の臨床像は多様であることが知られている。

出典

img1:  著者提供
 
 
 
  1. 進行性核上性麻痺は、指定難病であり、その一部(modified Rankin Scale、食事・栄養、呼吸のそれぞれの評価スケールを用いて、いずれかが3以上)などは、申請し認定されると保険料の自己負担分の一部が公費負担として助成される。(平成27年1月施行)
  1. 難病法に基づく医療費助成制度
 
  1. PSPはタウオパチーに分類される(推奨度1)。(参考文献:[4]
  1. まとめ:PSPはアルツハイマー病、皮質基底核変性症、ピック病などとともにタウオパチーに分類される。
  1. 代表事例:神経病理学的には、淡蒼球、視床下核、黒質、四丘体、橋被蓋、小脳歯状核に特に目立つ、大脳深部と脳幹の広範な領域の神経細胞脱落、グリオーシス、神経原線維変化の出現を特徴とする。また微小管結合蛋白質の1つで、微小管の形成を促進し安定化する働きを持っているタウと呼ばれる蛋白質が主要構成成分である、房状の形状をした星細胞(tuft-shaped astrocyte)がPSPに特異性の高い所見である。PSPはアルツハイマー病などと並んでタウ蛋白の異常を認める疾患としてタウオパチーに分類され、4リピートタウの蓄積を特徴とする。
  1. 結論:主要な構成成分がタウである房状の形状をした星細胞がPSPに特異性の高い所見である。
 
  1. 典型的な進行性核上性麻痺(Richardson症候群)を理解する必要がある(推奨度1)。(参考文献:[5][6]
  1. 病歴:71歳時に歩行障害と易転倒性で発症。構音障害も認めた。72歳時には嚥下障害と垂直性核上性眼球運動障害も出現。転倒しても注意が生じることなく転倒を繰り返した。76歳から肺炎を繰り返すようになり、78歳で死亡。
  1. 診察:進行性核上性麻痺(PSP)(臨床診断と病例診断が一致)
  1. 診断のためのテストとその結果:L-ドパは無効であった。病初期から易転倒性があり、構音障害も認め、来院時の頭部MRI T1矢状断にて橋腹側の膨らみの保たれた中脳被蓋の萎縮を認めた。その後、核上性眼球運動障害が出現し、経時的に撮影したMRIにて中脳被蓋の萎縮の進行も認め、臨床的にPSPを診断した。(<図表>
  1. 治療:L-ドパ製剤は無効で、その他の薬剤も奏効しなかった。誤嚥性肺炎に対しては、胃瘻を増設したがそれでも肺炎を繰り返した。
  1. 転帰:全経過7年で死亡。剖検にてPSPと診断した。
  1. コメント:本例はRichardsonらが提唱した典型的なPSP症例である。初期から易転倒性、構音障害、嚥下障害を認める場合には、パーキンソン病よりも進行性核上性麻痺や多系統萎縮症を考えるべきである。2~3年の観察期間中に垂直性核上性眼球運動障害を認めた場合にはPSPを強く疑う。
問診・診察のポイント  
  1. 発症1年以内の易転倒性を伴う姿勢反射障害の出現に留意する。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

まずは15日間無料トライアル
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: Günter U Höglinger, Gesine Respondek, Maria Stamelou, Carolin Kurz, Keith A Josephs, Anthony E Lang, Brit Mollenhauer, Ulrich Müller, Christer Nilsson, Jennifer L Whitwell, Thomas Arzberger, Elisabet Englund, Ellen Gelpi, Armin Giese, David J Irwin, Wassilios G Meissner, Alexander Pantelyat, Alex Rajput, John C van Swieten, Claire Troakes, Angelo Antonini, Kailash P Bhatia, Yvette Bordelon, Yaroslau Compta, Jean-Christophe Corvol, Carlo Colosimo, Dennis W Dickson, Richard Dodel, Leslie Ferguson, Murray Grossman, Jan Kassubek, Florian Krismer, Johannes Levin, Stefan Lorenzl, Huw R Morris, Peter Nestor, Wolfgang H Oertel, Werner Poewe, Gil Rabinovici, James B Rowe, Gerard D Schellenberg, Klaus Seppi, Thilo van Eimeren, Gregor K Wenning, Adam L Boxer, Lawrence I Golbe, Irene Litvan, Movement Disorder Society-endorsed PSP Study Group
雑誌名: Mov Disord. 2017 Jun;32(6):853-864. doi: 10.1002/mds.26987. Epub 2017 May 3.
Abstract/Text BACKGROUND: PSP is a neuropathologically defined disease entity. Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP, have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardson's syndrome.
OBJECTIVE: We aimed to provide an evidence- and consensus-based revision of the clinical diagnostic criteria for PSP.
METHODS: We searched the PubMed, Cochrane, Medline, and PSYCInfo databases for articles published in English since 1996, using postmortem diagnosis or highly specific clinical criteria as the diagnostic standard. Second, we generated retrospective standardized clinical data from patients with autopsy-confirmed PSP and control diseases. On this basis, diagnostic criteria were drafted, optimized in two modified Delphi evaluations, submitted to structured discussions with consensus procedures during a 2-day meeting, and refined in three further Delphi rounds.
RESULTS: Defined clinical, imaging, laboratory, and genetic findings serve as mandatory basic features, mandatory exclusion criteria, or context-dependent exclusion criteria. We identified four functional domains (ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction) as clinical predictors of PSP. Within each of these domains, we propose three clinical features that contribute different levels of diagnostic certainty. Specific combinations of these features define the diagnostic criteria, stratified by three degrees of diagnostic certainty (probable PSP, possible PSP, and suggestive of PSP). Clinical clues and imaging findings represent supportive features.
CONCLUSIONS: Here, we present new criteria aimed to optimize early, sensitive, and specific clinical diagnosis of PSP on the basis of currently available evidence. © 2017 International Parkinson and Movement Disorder Society.

© 2017 International Parkinson and Movement Disorder Society.
PMID 28467028  Mov Disord. 2017 Jun;32(6):853-864. doi: 10.1002/mds.26・・・
著者: Max-Joseph Grimm, Gesine Respondek, Maria Stamelou, Thomas Arzberger, Leslie Ferguson, Ellen Gelpi, Armin Giese, Murray Grossman, David J Irwin, Alexander Pantelyat, Alex Rajput, Sigrun Roeber, John C van Swieten, Claire Troakes, Angelo Antonini, Kailash P Bhatia, Carlo Colosimo, Thilo van Eimeren, Jan Kassubek, Johannes Levin, Wassilios G Meissner, Christer Nilsson, Wolfgang H Oertel, Ines Piot, Werner Poewe, Gregor K Wenning, Adam Boxer, Lawrence I Golbe, Keith A Josephs, Irene Litvan, Huw R Morris, Jennifer L Whitwell, Yaroslau Compta, Jean-Christophe Corvol, Anthony E Lang, James B Rowe, Günter U Höglinger, Movement Disorder Society-endorsed PSP Study Group
雑誌名: Mov Disord. 2019 Aug;34(8):1228-1232. doi: 10.1002/mds.27666. Epub 2019 Mar 18.
Abstract/Text BACKGROUND: The Movement Disorder Society criteria for progressive supranuclear palsy define diagnostic allocations, stratified by certainty levels and clinical predominance types. We aimed to study the frequency of ambiguous multiple allocations and to develop rules to eliminate them.
METHODS: We retrospectively collected standardized clinical data by chart review in a multicenter cohort of autopsy-confirmed patients with progressive supranuclear palsy, to classify them by diagnostic certainty level and predominance type and to identify multiple allocations.
RESULTS: Comprehensive data were available from 195 patients. More than one diagnostic allocation occurred in 157 patients (80.5%). On average, 5.4 allocations were possible per patient. We developed four rules for Multiple Allocations eXtinction (MAX). They reduced the number of patients with multiple allocations to 22 (11.3%), and the allocations per patient to 1.1.
CONCLUSIONS: The proposed MAX rules help to standardize the application of the Movement Disorder Society criteria for progressive supranuclear palsy. © 2019 International Parkinson and Movement Disorder Society.

© 2019 International Parkinson and Movement Disorder Society.
PMID 30884545  Mov Disord. 2019 Aug;34(8):1228-1232. doi: 10.1002/mds.・・・
著者: Farwa Ali, Peter R Martin, Hugo Botha, J Eric Ahlskog, James H Bower, Joseph Y Masumoto, Demetrius Maraganore, Anhar Hassan, Scott Eggers, Bradley F Boeve, David S Knopman, Daniel Drubach, Ronald C Petersen, Erika Driver Dunkley, Jay van Gerpen, Ryan Uitti, Jennifer L Whitwell, Dennis W Dickson, Keith A Josephs
雑誌名: Mov Disord. 2019 Aug;34(8):1144-1153. doi: 10.1002/mds.27619. Epub 2019 Feb 6.
Abstract/Text BACKGROUND: In 2017, the International Parkinson and Movement Disorder Society put forward new clinical criteria for the diagnosis of PSP, recognizing diverse PSP phenotypes. In this study, we compared the sensitivity and specificity of the new criteria with the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria at different times.
METHODS: Patients with clinical parkinsonism, clinical and/or neuropathological diagnosis of PSP, were identified from the Society for Progressive Supranuclear Palsy brain bank. All patients had neuropathologic diagnoses and detailed clinical examination performed by a neurologist at 1 of the 3 Mayo Clinic sites, in Florida, Arizona, and Minnesota. Clinical symptoms and signs were abstracted retrospectively in a blinded fashion and used to determine whether patients met either diagnostic criterion. Patients were divided into early and late disease stage groups using a 3-year cutoff.
RESULTS: A total of 129 patients were included, of whom 66 had PSP pathology (51%). The remainder had other neurodegenerative diseases. The overall sensitivity of the International Parkinson and Movement Disorder Society criteria was 87.9%, compared with 45.5% for the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria, whereas the specificity of the International Parkinson and Movement Disorder Society probable PSP criteria was 85.7%, compared with 90.5% for the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy. Individual patients were noted to have features of multiple PSP phenotypes.
CONCLUSION: The International Parkinson and Movement Disorder Society criteria recognize several phenotypes of progressive supranuclear palsy and hence have higher sensitivity than the previous criteria. © 2019 International Parkinson and Movement Disorder Society.

© 2019 International Parkinson and Movement Disorder Society.
PMID 30726566  Mov Disord. 2019 Aug;34(8):1144-1153. doi: 10.1002/mds.・・・
著者: J C STEELE, J C RICHARDSON, J OLSZEWSKI
雑誌名: Arch Neurol. 1964 Apr;10:333-59.
Abstract/Text
PMID 14107684  Arch Neurol. 1964 Apr;10:333-59.
著者: I Litvan, Y Agid, D Calne, G Campbell, B Dubois, R C Duvoisin, C G Goetz, L I Golbe, J Grafman, J H Growdon, M Hallett, J Jankovic, N P Quinn, E Tolosa, D S Zee
雑誌名: Neurology. 1996 Jul;47(1):1-9.
Abstract/Text To improve the specificity and sensitivity of the clinical diagnosis of progressive supranuclear palsy (PSP, Steele-Richardson-Olszewski syndrome), the National Institute of Neurological Disorders and Stroke (NINDS) and the Society for PSP, Inc. (SPSP) sponsored an international workshop to develop an accurate and universally accepted set of criteria for this disorder. The NINDS-SPSP criteria, which were formulated from an extensive review of the literature, comparison with other previously published sets of criteria, and the consensus of experts, were validated on a clinical data set from autopsy-confirmed cases of PSP. The criteria specify three degrees of diagnostic certainty: possible PSP, probable PSP, and definite PSP. Possible PSP requires the presence of a gradually progressive disorder with onset at age 40 or later, either vertical supranuclear gaze palsy or both slowing of vertical saccades and prominent postural instability with falls in the first year of onset, as well as no evidence of other diseases that could explain these features. Probable PSP requires vertical supranuclear gaze palsy, prominent postural instability, and falls in the first year of onset, as well as the other features of possible PSP. Definite PSP requires a history of probable or possible PSP and histopathologic evidence of typical PSP. Criteria that support the diagnosis of PSP, and that exclude diseases often confused with PSP, are presented. The criteria for probable PSP are highly specific, making them suitable for therapeutic, analytic epidemiologic, and biologic studies, but not very sensitive. The criteria for possible PSP are substantially sensitive, making them suitable for descriptive epidemiologic studies, but less specific. An appendix provides guidelines for diagnosing and monitoring clinical disability in PSP.

PMID 8710059  Neurology. 1996 Jul;47(1):1-9.
著者: Naoko Kato, Kimihito Arai, Takamichi Hattori
雑誌名: J Neurol Sci. 2003 Jun 15;210(1-2):57-60.
Abstract/Text Rostral midbrain atrophy in progressive supranuclear palsy (PSP) is detected by mid-sagittal plain magnetic resonance imaging (MRI). The shape of the atrophy looks like the bill of a hummingbird (hummingbird sign). We studied this sign to elucidate the nature of midbrain atrophy in PSP. Eight patients with PSP, 12 with Parkinson's disease (PD), and 10 normal controls were studied. Using mid-sagittal plain MRI, we measured the rostral and caudal midbrain tegmentum (MT), superior and inferior colliculus, pontine base, and tegmentum. We compared the length of the interpeduncular fossa, which is posterior to the mammillary body, to the diameter of the midbrain tegmentum. The multiple comparison method was used for the statistical analysis. The hummingbird sign was demonstrated in all of the PSP patients studied, and it was not observed in PD patients nor in normal controls. The hummingbird sign in the PSP patients was due to the atrophy of the midbrain tegmentum (rostral and caudal) and to a relative increase in the length of the interpeduncular fossa over that of the anteroposterior diameter of the midbrain tegmentum. The hummingbird sign, which represents the atrophy of the rostral midbrain tegmentum, strongly suggests the involvement of the rostral interstitial nucleus of the medial longitudinal fasciculus in patients with PSP. Demonstration of a hummingbird sign on MRI is thought to be useful for a diagnosis of PSP.

PMID 12736089  J Neurol Sci. 2003 Jun 15;210(1-2):57-60.
著者: H Oba, A Yagishita, H Terada, A J Barkovich, K Kutomi, T Yamauchi, S Furui, T Shimizu, M Uchigata, K Matsumura, M Sonoo, M Sakai, K Takada, A Harasawa, K Takeshita, H Kohtake, H Tanaka, S Suzuki
雑誌名: Neurology. 2005 Jun 28;64(12):2050-5. doi: 10.1212/01.WNL.0000165960.04422.D0.
Abstract/Text OBJECTIVE: To evaluate the area of the midbrain and pons on mid-sagittal MRI in patients with progressive supranuclear palsy (PSP), Parkinson disease (PD), and multiple-system atrophy of the Parkinson type (MSA-P), compare these appearances and values with those of normal control subjects, and establish diagnostic MRI criteria for the diagnosis of PSP.
METHODS: The authors prospectively studied MRI of 21 patients with PSP, 23 patients with PD, 25 patients with MSA-P, and 31 age-matched normal control subjects. The areas of the midbrain tegmentum and the pons were measured on mid-sagittal MRI using the display tools of a workstation. The ratio of the area of the midbrain to the area of the pons was also evaluated in all subjects.
RESULTS: The average midbrain area of the patients with PSP (56.0 mm2) was significantly smaller than that of the patients with PD (103.0 mm2) and MSA-P (97.2 mm2) and that of the age-matched control group (117.7 mm2). The values of the area of the midbrain showed no overlap between patients with PSP and patients with PD or normal control subjects. However, patients with MSA-P showed some overlap of the values of individual areas with values from patients with PSP. The ratio of the area of the midbrain to the area of pons in the patients with PSP (0.124) was significantly smaller than that in those with PD (0.208) and MSA-P (0.266) and in normal control subjects (0.237). Use of the ratio allowed differentiation between the PSP group and the MSA-P group.
CONCLUSION: The area of the midbrain on mid-sagittal MRI can differentiate PSP from PD, MSA-P, and normal aging.

PMID 15985570  Neurology. 2005 Jun 28;64(12):2050-5. doi: 10.1212/01.W・・・
著者: David R Williams, Andrew J Lees
雑誌名: Lancet Neurol. 2009 Mar;8(3):270-9. doi: 10.1016/S1474-4422(09)70042-0.
Abstract/Text Progressive supranuclear palsy (PSP) is a clinical syndrome comprising supranuclear palsy, postural instability, and mild dementia. Neuropathologically, PSP is defined by the accumulation of neurofibrillary tangles. Since the first description of PSP in 1963, several distinct clinical syndromes have been described that are associated with PSP; this discovery challenges the traditional clinicopathological definition and complicates diagnosis in the absence of a reliable, disease-specific biomarker. We review the emerging nosology in this field and contrast the clinical and pathological characteristics of the different disease subgroups. These new insights emphasise that the pathological events and processes that lead to the accumulation of phosphorylated tau protein in the brain are best considered as dynamic processes that can develop at different rates, leading to different clinical phenomena. Moreover, for patients for whom the diagnosis is unclear, clinicians must continue to describe accurately the clinical picture of each individual, rather than label them with inaccurate diagnostic categories, such as atypical parkinsonism or PSP mimics. In this way, the development of the clinical features can be informative in assigning less common nosological categories that give clues to the underlying pathology and an understanding of the expected clinical course.

PMID 19233037  Lancet Neurol. 2009 Mar;8(3):270-9. doi: 10.1016/S1474-・・・
著者: David R Williams, Andrew J Lees
雑誌名: Mov Disord. 2010 Feb 15;25(3):357-62. doi: 10.1002/mds.22977.
Abstract/Text Progressive supranuclear palsy-parkinsonism (PSP-P) is a primary tauopathy characterised by neurofibrillary degeneration, which is frequently mistaken for Parkinson's disease (PD), multiple system atrophy (MSA), and vascular parkinsonism (VP) at presentation. The aim of this study was to identify particular clinical features (green flags) that may be helpful in differentiating PSP-P from these other disorders. We identified 37 patients with PSP-P from 726 patients archived at the Queen Square Brain Bank. Using a retrospective case notes review the clinical features were compared between the PSP-P group and Lewy body associated parkinsonism (PD, n = 444 and dementia with Lewy bodies (DLB), n = 46), MSA (n = 90), and VP (n = 19), using the chi(2)-test for proportions for a two-by-two contingency table. The sensitivity, specificity, and positive predictive values (PPV) and negative predictive values (NPV) were calculated for individual clinical features. A specificity of >0.85 or a PPV of >0.85 were considered reliable discriminators. No clinical features were predictive of PSP-P, but late drug induced dyskinesias (specificity 0.92, PPV 0.99), late autonomic dysfunction (specificity 0.94, PPV 0.99) and any visual hallucinations (specificity 0.94, PPV 0.99) were better in distinguishing PD and PSP-P than predicted using operational diagnostic criteria for PD. PSP-P shares many clinical features with PD and DLB, MSA and VP, but visual hallucinations, drug induced dyskinesias and autonomic dysfunction are very uncommon and may be helpful exclusion criteria.

(c) 2010 Movement Disorder Society.
PMID 20108379  Mov Disord. 2010 Feb 15;25(3):357-62. doi: 10.1002/mds.・・・
著者: Sam Birdi, Ali H Rajput, Mark Fenton, Jeffery R Donat, Bohdan Rozdilsky, Christopher Robinson, Rob Macaulay, David George
雑誌名: Mov Disord. 2002 Nov;17(6):1255-64. doi: 10.1002/mds.10211.
Abstract/Text We evaluated 16 (15 men, 1 woman) autopsy-verified progressive supranuclear palsy (PSP) cases during 31 years (1969-2000) for clinical diagnosis and the course of the disease. The onset was gait difficulty or postural instability in 9 (56.3%), general motor slowing in 3 (18.8%), and tremor in 2. One case had onset with cognitive decline and 1 as hemidystonia. Four cases had supranuclear ophthalmoplegia (SNO) at the first assessment and were diagnosed as PSP. By last assessment, PSP diagnosis was made in 4 additional cases, but in 8 (50%) who never manifested ophthalmoplegia (mean 9.8 years after onset), PSP diagnosis was not made. Other manifestations included bulbar symptoms in 13 (81.3%), and cognitive impairment in 10 (62.5%) during the course of illness. Fifteen cases received levodopa, amantadine, anticholinergics, dopamine agonists, and selegiline in different combinations with symptomatic benefit in 9 of 15 (60%). Five had some improvement on levodopa alone and 3 showed more improvement when a dopamine agonist was added to levodopa. In general, the benefit was minimal and occurred only early in the course of illness. The mean age at onset was 63.7 (range, 53-85) years. Mean duration at PSP diagnosis was 4.8 (range, 2-11) years. Mean survival was 8.6 (range, 3-24) years and mean age at death was 72.3 (range, 60-89) years. When the different diagnostic criteria recommended in the literature were used, the accuracy of clinical diagnosis did not improve substantially.

Copyright 2002 Movement Disorder Society
PMID 12465065  Mov Disord. 2002 Nov;17(6):1255-64. doi: 10.1002/mds.10・・・
著者: David R Williams, Janice L Holton, Kate Strand, Tamas Revesz, Andrew J Lees
雑誌名: Mov Disord. 2007 Nov 15;22(15):2235-41. doi: 10.1002/mds.21698.
Abstract/Text The clinical syndrome of pure akinesia has most often been associated with progressive supranuclear palsy (PSP) and is characterized by difficulty initiating gait and "freezing" during walking, writing and speaking. Similar syndromes have been described under the rubrics of primary progressive freezing gait and primary gait ignition failure. We investigated the specificity of the clinical syndrome of pure akinesia with gait freezing (PAGF) for PSP-tau pathology. Among 749 patients archived at the QSBB, only 7 fulfilled proposed diagnostic criteria of: gradual onset of freezing of gait or speech; absent limb rigidity and tremor; no sustained response to levodopa; and no dementia or ophthalmoplegia in the first 5 years of disease. In these cases detailed pathological examination was performed. PSP was the pathological diagnosis in six patients, and Parkinson's disease (PD) in the seventh. As defined, this syndrome had a positive predictive value of 86% for PSP-tau pathology. In the cases with PSP there were no additional features of coexistent vascular or PD and the median PSP-tau score was 3, reflecting relative mild tau load. The clinical syndrome of PAGF appears to have a high specificity for PSP-tau pathology. This relatively uncommon presentation of PSP-tau pathology has less severe tau accumulation than in the more common, "classic" PSP clinical phenotype: Richardson's disease.

(c) 2007 Movement Disorder Society.
PMID 17712855  Mov Disord. 2007 Nov 15;22(15):2235-41. doi: 10.1002/md・・・
著者: Masato Kanazawa, Takayoshi Shimohata, Yasuko Toyoshima, Mari Tada, Akiyoshi Kakita, Takashi Morita, Tetsutaro Ozawa, Hitoshi Takahashi, Masatoyo Nishizawa
雑誌名: Mov Disord. 2009 Jul 15;24(9):1312-8. doi: 10.1002/mds.22583.
Abstract/Text The clinical heterogeneity of progressive supranuclear palsy (PSP), which is classified as classic Richardson's syndrome (RS) and PSP-Parkinsonism (PSP-P), has been previously discussed. We retrospectively analyzed 22 consecutive Japanese patients with pathologically proven PSP to investigate the clinicopathological heterogeneity. We investigated the clinical features both early in and at any time during the disease course. The pathological severities of neuronal loss with gliosis and tau pathology were also evaluated. On the basis of the clinical features, 10 patients were categorized as having RS, and 8 were categorized as having PSP-P. Four patients presenting with cerebellar ataxia or cerebral cortical signs were categorized as having unclassifiable PSP. Among them, 3 developed cerebellar ataxia as the initial and principal symptom. Notably, tau-positive inclusion bodies in Purkinje cells were significantly more frequently observed in the patients with cerebellar ataxia than in those without cerebellar ataxia. All the patients with cerebellar ataxia exhibited more neuronal loss with gliosis and higher densities of coiled bodies in the cerebellar dentate nucleus than those without cerebellar ataxia. This study confirms the wide spectrum of clinicopathological manifestations associated with PSP regardless of different ethnic origin, and demonstrates that PSP patients manifest cerebellar ataxia.

2009 Movement Disorder Society.
PMID 19412943  Mov Disord. 2009 Jul 15;24(9):1312-8. doi: 10.1002/mds.・・・
著者: E R Maher, A J Lees
雑誌名: Neurology. 1986 Jul;36(7):1005-8.
Abstract/Text We analyzed the clinical features and natural history of 52 consecutive patients with the Steele-Richardson-Olszewski syndrome. The most common symptoms at onset were unsteady gait, backward falls because of poor balance, visual disturbances, slurred speech, and forgetfulness. The median duration from onset to death was 5.9 years, with a median survival after diagnosis of only 1.8 years. Bronchopneumonia was the usual cause of death recorded on death certificates.

PMID 3714047  Neurology. 1986 Jul;36(7):1005-8.
著者: L I Golbe, P H Davis, B S Schoenberg, R C Duvoisin
雑誌名: Neurology. 1988 Jul;38(7):1031-4.
Abstract/Text We surveyed neurologists and chronic care facilities in and near two New Jersey counties with a combined population of 799,022, regarding cases of progressive supranuclear palsy. All suspected cases were examined personally, using rigid criteria. The prevalence ratio was 1.39/100,000. A total of 50 New Jersey cases yielded median intervals to onset of requiring gait assistance, 3.1 years; visual symptoms, 3.9 years; dysarthria, 3.4 years; dysphagia, 4.4 years; requiring wheelchair, 8.2 years; and death, 9.7 years.

PMID 3386818  Neurology. 1988 Jul;38(7):1031-4.
著者: Lawrence I Golbe, Pamela A Ohman-Strickland
雑誌名: Brain. 2007 Jun;130(Pt 6):1552-65. doi: 10.1093/brain/awm032. Epub 2007 Apr 2.
Abstract/Text We devised a Progressive Supranuclear Palsy (PSP) Rating Scale comprising 28 items in six categories: daily activities (by history), behaviour, bulbar, ocular motor, limb motor and gait/midline. Scores range from 0 to 100, each item graded 0-2 (six items) or 0-4 (22 items). Inter-rater reliability is good, with intra-class correlation coefficient for the overall scale of 0.86 (95% CI 0.65-0.98). A single examiner applied the PSPRS at every visit for 162 patients. Mean rate of progression was 11.3 (+/-11.0) points per year. Neither onset age nor gender correlated well with rate of progression. Median actuarially corrected survival was 7.3 years. The PSPRS score was a good independent predictor of subsequent survival (P < 0.0001). For example, for patients with scores from 40 to 49, 3-year survival was 41.9% (95% CI 31.0-56.6) but 4-year survival was only 17.9% (95% CI 10.2-31.5). For those patients, likelihood or retaining some gait function was 51.7% (40.0-66.9) at 1 year but only 6.5% (1.8-23.5) at 3 years. We conclude that the PSPRS is a practical measure that is sensitive to disease progression and could be useful as a dependent variable in observational or interventional trials and as an indicator of prognosis in clinical practice.

PMID 17405767  Brain. 2007 Jun;130(Pt 6):1552-65. doi: 10.1093/brain/a・・・
著者: Richard G Brown, Lucette Lacomblez, Bernard G Landwehrmeyer, Thomas Bak, Ingo Uttner, Bruno Dubois, Yves Agid, Albert Ludolph, Gilbert Bensimon, Christine Payan, Nigel P Leigh, NNIPPS Study Group
雑誌名: Brain. 2010 Aug;133(Pt 8):2382-93. doi: 10.1093/brain/awq158. Epub 2010 Jun 24.
Abstract/Text This article reports the severity and profile of neuropsychological impairment on a prevalent cohort of patients with a clinical diagnosis of either multiple system atrophy (n=372) or progressive supranuclear palsy (n=311) from the Neuroprotection and Natural History in Parkinson Plus Syndromes cohort. The Dementia Rating Scale and Frontal Assessment Battery were used to assess global cognition and executive dysfunction. For the Dementia Rating Scale impairment was observed in approximately 57% of the progressive supranuclear palsy group and 20% of the multiple system atrophy group. In the former, impairment in a single cognitive domain was observed in 40%, with the same number showing impairment in multiple domains, while in the latter the figures were 28.6 and 13.5%, respectively. On the Frontal Assessment Battery, impairment was observed in 62.0% of patients with progressive supranuclear palsy and 31.8% of those with multiple system atrophy. Although the progressive supranuclear palsy group performed worse overall, the cognitive profiles of the two groups on the Dementia Rating Scale subscales were identical, with the main impairment of the Initiation and Perseveration subscale. The impaired patients in the two groups were largely indistinguishable, qualitatively and quantitatively. Impairment was associated with greater age and clinical disability in both groups and was evident even in the early stages (22% in multiple system atrophy and 50% in progressive supranuclear palsy). Where a pathological diagnosis was available, the original clinical diagnosis was confirmed in the majority of cases, including those with significant cognitive impairment. The rate of impairment in those with a confirmed pathological diagnosis was comparable to that of the sample as a whole. These results demonstrate, in the largest prospectively recruited cohort of patients with progressive supranuclear palsy and multiple system atrophy studied to date, the existence of a cognitive profile similar to that previously reported in idiopathic Parkinson's disease. The results indicate a high level of cognitive impairment associated with progressive supranuclear palsy, but also point to comparable dysfunction in a substantial proportion of the patients with multiple system atrophy. Significant cognitive impairment appears consistent with a diagnosis of multiple system atrophy, even early in the disease, with important implications for diagnosis, research and management.

PMID 20576697  Brain. 2010 Aug;133(Pt 8):2382-93. doi: 10.1093/brain/a・・・
著者: Harro Seelaar, Jonathan D Rohrer, Yolande A L Pijnenburg, Nick C Fox, John C van Swieten
雑誌名: J Neurol Neurosurg Psychiatry. 2011 May;82(5):476-86. doi: 10.1136/jnnp.2010.212225. Epub 2010 Oct 22.
Abstract/Text Frontotemporal dementia (FTD) is the second most common young-onset dementia and is clinically characterised by progressive behavioural change, executive dysfunction and language difficulties. Three clinical syndromes, behavioural variant FTD, semantic dementia and progressive non-fluent aphasia, form part of a clinicopathological spectrum named frontotemporal lobar degeneration (FTLD). The classical neuropsychological phenotype of FTD has been enriched by tests exploring Theory of Mind, social cognition and emotional processing. Imaging studies have detailed the patterns of atrophy associated with different clinical and pathological subtypes. These patterns offer some diagnostic utility, while measures of progression of atrophy may be of use in future trials. 30-50% of FTD is familial, and mutations in two genes, microtubule associated protein tau and Progranulin (GRN), account for about half of these cases. Rare defects in VCP, CHMP2B, TARDP and FUS genes have been found in a small number of families. Linkage to chromosome 9p13.2-21.3 has been established in familial FTD with motor neuron disease, although the causative gene is yet to be identified. Recent developments in the immunohistochemistry of FTLD, and also in amyotrophic lateral sclerosis (ALS), have led to a new pathological nomenclature. The two major groups are those with tau-positive inclusions (FTLD-tau) and those with ubiquitin-positive and TAR DNA-binding protein of 43 kDa (TDP-43) positive inclusions (FTLD-TDP). Recently, a new protein involved in familial ALS, fused in sarcoma (FUS), has been found in FTLD patients with ubiquitin-positive and TDP-43-negative inclusions. In this review, the authors discuss recent clinical, neuropsychological, imaging, genetic and pathological developments that have changed our understanding of FTD, its classification and criteria. The potential to establish an early diagnosis, predict underlying pathology during life and quantify disease progression will all be required for disease-specific therapeutic trials in the future.

PMID 20971753  J Neurol Neurosurg Psychiatry. 2011 May;82(5):476-86. d・・・
著者: K Kompoliti, C G Goetz, I Litvan, K Jellinger, M Verny
雑誌名: Arch Neurol. 1998 Aug;55(8):1099-102.
Abstract/Text BACKGROUND: To our knowledge, previous reports on drug treatment in progressive supranuclear palsy have not evaluated autopsy-confirmed cases.
OBJECTIVE: To evaluate pharmacological treatment responses from detailed clinical records in patients with autopsy-confirmed progressive supranuclear palsy.
SUBJECTS AND METHODS: We reviewed medical records for clinical presentation and pharmacological response in 12 patients with autopsy-confirmed progressive supranuclear palsy diagnosed using the National Institute of Neurological Disorders and Stroke pathologic criteria. For each drug class, exposure, global positive response, and specific positive response (parkinsonism, other movement disorders, or gaze dysfunction) were recorded.
RESULTS: Drug classes examined were dopaminergics (all patients), tricyclics (3 patients), methysergide maleate (3 patients), 5-hydroxytryptophan (2 patients), and anticholinergics and selective serotonin inhibitors (1 patient). Positive clinical response was detected in 7 of the patients receiving dopaminergic drugs and in 1 patient each receiving tricyclics, methysergide, and 5-hydroxytryptophan, respectively. None of the patients responded markedly however, and there was no persistent beneficial effect. Use of dopaminergic drugs most frequently improved parkinsonian features, but disabling adverse effects included orthostatic hypotension (6 patients), hallucinations and delusions (3 patients), gastrointestinal complaints (3 patients), and dizziness (1 patient). Only 1 patient developed dyskinesia.
CONCLUSION: Use of antiparkinsonian medications and other neurotransmitter replacement therapies was largely ineffective and caused frequent adverse effects in this series of patients with autopsy-confirmed with progressive supranuclear palsy.

PMID 9708960  Arch Neurol. 1998 Aug;55(8):1099-102.
著者: David R Williams, Rohan de Silva, Dominic C Paviour, Alan Pittman, Hilary C Watt, Linda Kilford, Janice L Holton, Tamas Revesz, Andrew J Lees
雑誌名: Brain. 2005 Jun;128(Pt 6):1247-58. doi: 10.1093/brain/awh488. Epub 2005 Mar 23.
Abstract/Text The clinical diagnosis of progressive supranuclear palsy (PSP) relies on the identification of characteristic signs and symptoms. A proportion of pathologically diagnosed cases do not develop these classic features, prove difficult to diagnose during life and are considered as atypical PSP. The aim of this study was to examine the apparent clinical dichotomy between typical and atypical PSP, and to compare the biochemical and genetic characteristics of these groups. In 103 consecutive cases of pathologically confirmed PSP, we have identified two clinical phenotypes by factor analysis which we have named Richardson's syndrome (RS) and PSP-parkinsonism (PSP-P). Cases of RS syndrome made up 54% of all cases, and were characterized by the early onset of postural instability and falls, supranuclear vertical gaze palsy and cognitive dysfunction. A second group of 33 (32%) were characterized by asymmetric onset, tremor, a moderate initial therapeutic response to levodopa and were frequently confused with Parkinson's disease (PSP-P). Fourteen cases (14%) could not be separated according to these criteria. In RS, two-thirds of cases were men, whereas the sex distribution in PSP-P was even. Disease duration in RS was significantly shorter (5.9 versus 9.1 years, P < 0.001) and age at death earlier (72.1 versus 75.5 years, P = 0.01) than in PSP-P. The isoform composition of insoluble tangle-tau isolated from the basal pons also differed significantly. In RS, the mean four-repeat:three-repeat tau ratio was 2.84 and in PSP-P it was 1.63 (P < 0.003). The effect of the H1,H1 PSP susceptibility genotype appeared stronger in RS than in PSP-P (odds ratio 13.2 versus 4.5). The difference in genotype frequencies between the clinical subgroups was not significant. There were no differences in apolipoprotein E genotypes. The classic clinical description of PSP, which includes supranuclear gaze palsy, early falls and dementia, does not adequately describe one-third of cases in this series of pathologically confirmed cases. We propose that PSP-P represents a second discrete clinical phenotype that needs to be clinically distinguished from classical PSP (RS). The different tau isoform deposition in the basal pons suggests that this may ultimately prove to be a discrete nosological entity.

PMID 15788542  Brain. 2005 Jun;128(Pt 6):1247-58. doi: 10.1093/brain/a・・・
著者: J A Jackson, J Jankovic, J Ford
雑誌名: Ann Neurol. 1983 Mar;13(3):273-8. doi: 10.1002/ana.410130308.
Abstract/Text Among 415 patients with parkinsonism, 16 (3.9%) had findings of progressive supranuclear palsy (PSP). This report reviews the clinical features and response to drug therapy in those 16 patients. Anticholinergic drugs failed to benefit any of the 5 patients treated, while presynaptic dopaminergic drugs (Sinemet or amantadine) were beneficial in only 5 of 22 patient trials. Alternatively, dopamine agonists (bromocriptine and pergolide) caused improvement in 9 of 14 patient trials despite the fact that all but 1 of these patients had previously failed to respond to presynaptic dopaminergic drugs. Dopamine agonists such as bromocriptine and pergolide may be useful in some patients with PSP.

PMID 6847139  Ann Neurol. 1983 Mar;13(3):273-8. doi: 10.1002/ana.4101・・・
著者: H Watanabe, Y Arahata, M Tadokoro, T Kato, G Sobue
雑誌名: Rinsho Shinkeigaku. 2000 Nov;40(11):1130-2.
Abstract/Text We reported a 64-year-old woman in the early stage of progressive supranuclear palsy presenting as pure akinesia syndrome who showed marked improvement with tandospirone citrate. She revealed bradykinesia, severe frozen gait and disturbance of postural reflex without rigidity or tremor. Treatment with L-dopa and L-threo DOPS was not effective, but tandospirone citrate at a daily dosage of 30 mg significantly lessened the severity of frozen gait. Activation single photon emission computed tomography study with 99mTc-ethyl cysteinate dimer during gait revealed a significant increase in brain activity in the right cingulate cortex after tandospirone citrate treatment. The effect lasted ten months until neck rigidity and ventricular supranuclear palsy were evident.

PMID 11332196  Rinsho Shinkeigaku. 2000 Nov;40(11):1130-2.
著者: M Iijima, H Terashi, M Iwata
雑誌名: Rinsho Shinkeigaku. 2001 Feb-Mar;41(2-3):150-3.
Abstract/Text We reported a 74-year-old male case of progressive supranuclear palsy (PSP) who responded to tandospirone citrate, a serotonin receptor (5-HT1A) agonist. The patient manifested postural instability and gait disturbance at 71 years. Additionally, he showed vertical gaze paresis, regidity of the neck, extremities and trunk, bradykinesia and mild cognitive impairment. A brain MRI revealed moderate atrophy of bilateral frontal/temporal lobes and of midbrain tegmentum one year after the onset. The patient had been diagnosed as PSP and treated with L-DOPA. However, L-DOPA therapy showed only transient response for a few months. His symptoms deteriorated gradually, and he became unable to sit, stand up or walk by himself. Tandospirone citrate was additionally administered at 30 mg/day. Rigidity and bradykinesia were remarkably improved in two weeks after the start of tandospirone treatment. He became able to stand up and walk a short distance with supports in four weeks. Cognitive disturbance was also slightly improved. Tandospirone citrate was effective on our case of PSP, especially on rigidity. Our findings suggest that combination of levodopa and tandospirone citrate is a useful therapy for PSP.

PMID 11481861  Rinsho Shinkeigaku. 2001 Feb-Mar;41(2-3):150-3.
著者: Yasuhiro Fujino, Masashi Nakajima, Yoshio Tsuboi, Yasuhiko Baba, Tatsuo Yamada
雑誌名: Rinsho Shinkeigaku. 2002 Jan;42(1):42-4.
Abstract/Text BACKGROUND: Serotonin activity has been shown to be increased in the basal ganglia of patients with progressive supranuclear palsy (PSP), and may be responsible for its extrapyramidal features that do not respond to 1-dopa.
OBJECTIVE: To investigate clinical effectiveness of 5-HT1A agonist, tandospirone citrate (TC), on various clinical features of PSP.
METHOD: Clinical signs of eight patients (2 women and 6 men) who fulfilled NINDS-SPSP criteria of PSP were studied before and after administration of TC. Each of vertical gaze palsy, apraxia of eyelid opening, neck dystonia, bradykinesia, postural instability, gait disturbances, dysarthria, dysphagia, and bladder disturbances was graded, and evaluated before, and two and four weeks after oral administration of TC 30 mg/day.
RESULTS: TC was well tolerated in six patients for four weeks. The other two patients developed dizziness or liver dysfunction in the second week, and dropped out. Neck dystonia, postural instability, and bradykinesia were improved significantly in the fourth week. On the contrary, vertical gaze palsy, dysarthria, and dysphagia responded poorly to TC. Apraxia of eyelid opening was present in three patients, and was improved in two. Bladder disturbances were present in three patients, and did not respond to TC.
CONCLUSION: Among various clinical features in PSP, TC was effective preferentially on extrapyramidal ones. Suppression of serotonergic activities in the basal ganglia of PSP may be underlying in the effectiveness of this 5-HT1A agonist.

PMID 12355852  Rinsho Shinkeigaku. 2002 Jan;42(1):42-4.
著者: Tobias Warnecke, Stephan Oelenberg, Inga Teismann, Christina Hamacher, Hubertus Lohmann, Erich Bernd Ringelstein, Rainer Dziewas
雑誌名: Mov Disord. 2010 Jul 15;25(9):1239-45. doi: 10.1002/mds.23060.
Abstract/Text Dysphagia is a frequent and early symptom in progressive supranuclear palsy (PSP) predisposing patients to aspiration pneumonia. Fiberoptic endoscopic evaluation of swallowing (FEES) has emerged as a valuable apparative tool for objective evaluation of neurogenic dysphagia. This is the first study using FEES to investigate the nature of swallowing impairment in PSP. Eighteen consecutive PSP patients (mean age 69.7 +/- 9.0 years) were included. The salient findings of FEES in PSP patients were compared with those of 15 patients with Parkinson's disease (PD). In 7 PSP patients, a standardized FEES protocol was performed to explore levodopa (L-dopa) responsiveness of dysphagia. Most frequent abnormalities detected by FEES were bolus leakage, delayed swallowing reflex, and residues in valleculae and piriformes. Aspiration events with at least one food consistency occurred in nearly 30% of PSP patients. Significant pharyngeal saliva pooling was observed in 4 PSP patients. We found no difference of salient endoscopic findings between PSP and PD patients. Endoscopic dysphagia severity in PSP correlated positively with disease duration, clinical disability, and cognitive impairment. No correlation was found with dysarthria severity. In early PSP patients, swallowing dysfunction was solely characterized by liquid leakage with the risk of predeglutitive aspiration during the oral phase of swallowing. Two PSP patients showed relevant improvement of swallowing function after L-dopa challenge. Chin tuck-maneuver, hard swallow, and modification of food consistency were identified as the most effective therapeutic interventions. In conclusion, FEES assessment can deliver important findings for the diagnosis and refined therapy of dysphagia in PSP patients.

PMID 20629130  Mov Disord. 2010 Jul 15;25(9):1239-45. doi: 10.1002/mds・・・
著者: Ikuko Aiba, Yufuko Saito, Akiko Tamakoshi, Yukihiko Matsuoka
雑誌名: Rinsho Shinkeigaku. 2005 Aug;45(8):565-70.
Abstract/Text Survival and prognosis were investigated in 45 patients with progressive supranuclear palsy (including 10 autopsy cases) from April, 1991 to March, 2003 in Higashi Nagoya National Hospital. The subjects were 28 males, and 17 females. Mean age at onset was 64.9 years old (45-79 years old), and median survival time was 6 years. Age at onset, sex and clinical group due to NINDS-SPSP criteria ("probable" vs "possible") were not related to survival time. Among the symptoms and signs at onset, only dysphagia was related to prognosis. Dysphagia within the first year from onset reduced survival time (p < 0.0001).

PMID 16180703  Rinsho Shinkeigaku. 2005 Aug;45(8):565-70.
著者: K Kluin, S Gilman, N Foster, A Sima, C D'Amato, L Bruch, L Bluemlein, R Little, J Johanns
雑誌名: Arch Neurol. 2001 Feb;58(2):265-9.
Abstract/Text BACKGROUND: The dysarthria of progressive supranuclear palsy consists of prominent hypokinetic and spastic components with less prominent ataxic components.
OBJECTIVE: To correlate the types of dysarthria with neuropathological changes in patients with progressive supranuclear palsy.
DESIGN AND METHODS: In 14 patients with progressive supranuclear palsy, we correlated the perceptual speech findings with the neuropathological findings. A dysarthria assessment was performed a mean +/- SD of 31 +/- 15 months (range, 10-53 months) before death. The deviant speech dimensions were rated on a scale of 0 (normal) to 3 (severe). The neuropathological examination consisted of semiquantitative analysis of neuronal loss and gliosis by investigators (A.A.F.S., and L.A.B.) blinded to the clinical findings. Correlation and linear regression analysis were used to correlate the severity of the hypokinetic, spastic, and ataxic components with the degree of neuronal loss and gliosis in predetermined anatomical sites.
RESULTS: All patients had hypokinetic and spastic dysarthria, and 9 also had ataxic components. The severity of the hypokinetic components was significantly correlated with the degree of neuronal loss and gliosis in the substantia nigra pars compacta (r = 0.61, P =.02) and pars reticulata (r = 0.64, P =.01) but not in the subthalamic nucleus (r = 0.51, P =.07) or the striatum or globus pallidus (/r/<0.34, P>.20). The severity of the spastic and ataxic components was not significantly correlated with the neuropathological changes in the frontal cortex (r = 0.20, P =.50) and cerebellum (/r/<0.28, P>.33), respectively.
CONCLUSION: The hypokinetic dysarthria of progressive supranuclear palsy may result from degenerative changes in the substantia nigra pars compacta and pars reticulata and not from changes in the striatum or globus pallidus.

PMID 11176965  Arch Neurol. 2001 Feb;58(2):265-9.
著者: Jonathan D Rohrer, Dominic Paviour, Adolfo M Bronstein, Sean S O'Sullivan, Andrew Lees, Jason D Warren
雑誌名: Mov Disord. 2010 Jan 30;25(2):179-88. doi: 10.1002/mds.22946.
Abstract/Text There is currently considerable interest in the clinical spectrum of progressive nonfluent aphasia (PNFA) and progressive supranuclear palsy (PSP) and the intersection of these two entities. Here, we undertook a detailed prospective clinical, neuropsychological, and neuroimaging analysis of 14 consecutive patients presenting with PNFA to identify cases meeting clinical criteria for PSP. These patients had further detailed assessment of extrapyramidal and oculomotor functions. All patients had high-resolution MR brain volumetry and a cortical thickness analysis was undertaken on the brain images. Four patients presenting with PNFA subsequently developed features of a PSP syndrome, including a typical oculomotor palsy. The neuropsychological profile in these cases was similar to other patients with PNFA, however, with more marked reduction in propositional speech, fewer speech errors, less marked impairment of literacy skills but more severe associated deficits of episodic memory and praxis. These PSP-PNFA cases had less prominent midbrain atrophy but more marked prefrontal atrophy than a comparison group of five patients with pathologically confirmed PSP without PNFA and more prominent midbrain atrophy but less marked perisylvian atrophy than other PNFA cases. In summary, although the PSP-PNFA syndrome overlaps with PNFA without PSP, certain neuropsychological and neuroanatomical differences may help predict the development of a PSP syndrome.

(c) 2010 Movement Disorder Society.
PMID 20077483  Mov Disord. 2010 Jan 30;25(2):179-88. doi: 10.1002/mds.・・・

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから