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PSP

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PSP

  1. 1. Progressive supranuclear palsy 進行性核上麻痺
  2. 2. PSP; Steele-Richardson-Olszewski disease 成人発症の神経変性疾患; 早期からの姿勢不安定性, 垂直方向の核上性注視麻痺を特徴とする 臨床症状は特徴的であり, 眼は “Mona Lisa” stareと呼ばれ, 瞬きは少ない(0-4回/min). 頸部は後屈し, 声量は低下して不明瞭なうなり声に聞こえる. 動作は緩慢で, 後方に転倒しやすい. 下方視が困難であり, 嚥下機能も低下するため, 食事をよくこぼすようになる. 認知能も緩慢になるため, 返答や会話が遅くなる 複視や視野のぼやけ, 羞明, 不随意の眼瞼閉鎖は初期から出現する症状であり, しばしば眼科を受診する. 多系統萎縮症と異なり, 著名な起立性低血圧は稀 This review provides an update on progressive supranuclear palsy (PSP, or Steele-Richardson-Olszewski disease), an adult-onset neurodegenerative disorder characterised by early postural instability, which leads to falls, and a vertical supranuclear-gaze palsy. Recent epidemiological studies have shown that the disorder is more common than previously recognised, that it is commonly misdiagnosed, and that it may present to a wide range of hospital specialists. The diagnosis of PSP hinges on clinical acumen. Attempts to identify a suitable biomarker in the CSF or a specific and sensitive imaging or neurophysiological technique have so far failed to have a significant effect on the diagnostic process. Better understanding of the molecular pathology of PSP has highlighted the importance of tau-protein accumulation and tau-genotype susceptibility in its pathogenesis. No drug treatment significantly and consistently benefits patients, and ReviewProgressive supranuclear palsy Progressive supranuclear palsy: where are we now? David J Burn and Andrew J Lees Lancet Neurology 2002;1:359-69
  3. 3. PSPの疫学 頻度は報告により様々. 年々増加しており, 3-14/100000とされる. 後発年齢は60-65yrであり, 男女差は無し. 発症∼診断までの平均期間は3.6-4.9yrと診断がつかないことが多い 発症∼死亡までの平均期間は5.8-5.9yr程度. 初期診断で挙げられるものはParkinson’s disease(30%), Balance disorder(20%),  Stroke(10%), Depression(7%)が多い. 初期よりしっかりとPSPと診断される例は43%しかない.
  4. 4. PSPの診断 Possible PSP Mandatory inclusion criteria 徐々に増悪する症状, 発症は>=40yr, 発症から1yr以内に垂直性の核上性注視麻痺, 垂直方向のSaccade運動の緩慢, 姿勢不安定性の出現を認める. Mandatory exclusion criteria 最近の脳炎, alien limb syndrome, cortical sensory deficits, focal frontal/temporoparietal atrophy, Hallucination, ドパミン治療と関係のないdelusion, Alzheimerタイプの認知症, early cerebellar symptom, 説明困難なautonomic dysautonomiaの既往 Supportive features 左右対称のAkinesia/rigidity (近位優位), 頸位の異常(後方), LevodopaによるParkinsonism改善が乏しい, 早期の嚥下, 構音障害, 早期の認知症 無為, 思考の緩慢, 停止, 会話の減少, Frontal release signs Probable PSP Mandatory inclusion criteria 徐々に増悪する症状, 発症は>=40yr, 発症から1yr以内に垂直性の核上性注視麻痺, 垂直方向のSaccade運動の緩慢, 姿勢不安定性の出現を認める. Definite PSP Mandatory inclusion criteria 臨床的にProbable, Possible PSPであり, 組織所見でもPSPに矛盾しない 非典型的な症状も早期から認められる場合がある 片側性のDystonia, 上腕の浮動, 観念運動失行, 口蓋ミオクローヌスなど
  5. 5. PSP-CとPSP-P PSPには古典的なRichardson’s syndromeを呈するtype(Classical), Parkinsonismを早期から伴うtypeを認める. 101名の病理的に診断されたPSPのうち, 54%がPSP-C, 32%がPSP-P. 14%が分類不能. Brain (2005), 128, 1247–1258 PSP-C PSP-P P値 PSP-C PSP-P P値 転倒 85.7% 0% <0.001 100% 80.6% 0.001 認知障害 50.0% 0 <0.001 90.7% 51.6% <0.001 振戦 9.8% 39.1% 0.007 13.0% 43.8% 0.002 構音障害 32.5% 26.1% 0.406 90.2% 81.3% 0.242 嚥下障害 2.7% 4.3% 0.624 75.5% 56.3% 0.070 視覚障害 23.1% 4.3% 0.051 56.6% 34.4% 0.047 左右非対称性の発症 17.9% 45.0% 0.030 動作緩慢 75.6% 73.9% 0.880 98.2% 96.9% 0.685 固縮 39.5% 52.5% 0.333 98.1% 96.8% 0.687 姿勢反射障害 84.4% 7.7% <0.001 100% 96% 0.142 Extra-axial dystonia 0 8.7% 0.138 21.2% 42.4% 0.054 Supranuclear gaze palsy 70.0% 0 0.002 100% 71.4% <0.001 追視, saccade異常 63.6% 0 0.017 錐体路徴候 7.9% 4.3% 0.513 17.0% 15.6% 0.561 Levodopaへの反応性あり 14.3% 50.0% 0.005 1.9% 6.3% 0.323 早期 晩期 PSP-Pの発症早期では 古典的なPSP症状は認められない 転倒, 認知障害が乏しく, 晩期に出現する経過をとる. PSPでも様々な経過をとる.
  6. 6. PSPの検査 MRI所見 臨床的にPSPと診断された患者の70%がMRIで所見を認める. 中脳の直径(矢状断)<17mm, 中脳が高信号を呈する, 赤核の高信号 or 萎縮, 淡蒼球の高信号. T2強調画像で淡蒼球が高信号に写る; Myelinated fibreの減少とAstrocytosisの増加, その周辺の鉄沈着により低信号域を伴い, “eye of the tiger sign” と呼ばれる. これはHallervorden-Spatz syndromeで有名な所見.
  7. 7. 中脳-橋の矢状断面積 PSP患者21名, PD患者23名, MSA-P患者25名, Control 31名の Prospective Case-control study. (Neurology 2005;64:2050-5) MRI矢状断にて, 中脳-橋面積比を比較. 2本の補助線; 橋前上部のnotch - 四丘板と  それに平行となるような橋後下部のnotchを通る線 その線で区切られる中脳, 橋の面積を測定し, 比を各疾患で評価. Outcome; 中脳面積のみでみると, MSA-PとのOverlapがあるが, 中脳/橋 面積比ではPSPが群を抜いて低い. → 診断法として有用かも? ただし, Reference Standardが不明, またValidationも無し Group 中脳面積(mm2) 中脳/橋 比 PSP 56[33-66] 0.124[0.09-0.15] PD 103[86-136] 0.208[0.17-0.3] MSA-P 97.2[64-130] 0.266[0.18-0.49] Control 117.7[101-169] 0.236[0.18-0.32]
  8. 8. PSP 33名, PD 108名, MSA-P 19名, 健常人 50名のProspective study T1-WIにて, 橋断面積/中脳断面積 (P/M), MCP-width/SCP-width ratioを評価し, MR Parkinsonism Index = P/M x MCP/SCP を評価. (MCP; Middle cerebellar peduncles, 中小脳脚, SCP; Superior cerebellar peduncles, 上小脳脚) Radiology 2008;246:214-21 Figure 2 Figure 2: Sagittal and coronal T1-weighted volumetric spoiled gradient-echo MR images (15.2/6.8; section thickness, 0.6 mm; frequency- and phase-encoding ma- trix, 256ϫ 256; flip angle, 15°) show midbrain area(1), pons area(2), MCP width(3), and SCP width(4) in (a) a control participant and(b) a patient with PSP. Images show marked atrophy of both midbrain and SCP in the PSP patient in comparison with the healthy control participant. In the patient with PSP, values wereas follows: midbrain area, 60 mm2 ; pons area, 502 mm2 ; MCP width, 8.15 mm; and SCP width, 1.70 mm. In the control participant, values were as follows: midbrain area, 108 mm2 ; pons area, 478 mm2 ; MCP width, 10.05 mm; and SCP width, 4.10 mm. NEURORADIOLOGY:MR Parkinsonism Index for Differentiation of Diseases Quattrone et al 1) 中脳断面積, 2) 橋断面積, 3) 中小脳脚幅, 4) 上小脳脚幅 a)は健常人, b)はPSP患者
  9. 9. 各パラメータ MR Parkinsonism Index Cutoffと感度, 特異度. Radiology 2008;246:214-21was smaller than that in patients with PD (P Ͻ .001) and in control partici- pants (P Ͻ .001) (Fig 3). No difference, however, was observed between pa- tients with PD and control participants. There was some overlap of individual values among all groups (Fig 3). There was no significant difference between patients with possible PSP and patients with probable PSP. Sensitivity, specificity, and PPV of MCP/SCP for differentiating patients with PSP from those with PD, patients with PSP from those with MSA-P, and patients with PSP from control partici- pants varied at different cutoff levels (Table 4), and the optimal levels were 2.69 or greater, 2.43 or greater, and 2.69 or greater, respectively. MR parkinsonism index values.— Patients with PSP showed the highest MR parkinsonism index values with re- spect to all other groups (patients with PSP vs patients with MSA-P, P Ͻ .001; patients with PSP vs patients with PD, P Ͻ .001; patients with PSP vs control participants, P Ͻ .001) (Fig 3). There was no overlap of individual values for the MR parkinsonism index between the patients with PSP (median, 19.42; Table 2 Measurements for Brain Structures in Patients with PSP, MSA-P, and PD and Control Participants Group Midbrain Area (mm2 ) Pons Area (mm2 ) SCP Width (mm) MCP Width (mm) PSP patients (n ϭ 33) 63 (38–94) 406 (230–516) 2.4 (1.6–3.3) 7.0 (5.1–9.4) MSA-P patients (n ϭ 19) 110 (63–132) 343 (244–492) 2.9 (1.9–3.9) 5.9 (3.4–7.7) PD patients (n ϭ 108) 119 (70–163) 471 (372–615) 3.7 (3.0–4.8) 8.7 (8.1–10.2) Control participants (n ϭ 50) 122 (94–168) 469 (386–622) 3.8 (3.1–4.5) 8.8 (8.1–10.5) Note.—Values are medians, and numbers in parentheses are ranges. For all measurements, P Ͻ .001 (Kruskal-Wallis test). Table 3 Pairwise Comparisons between Groups Group Comparison Midbrain Area P Value Pons Area P Value SCP Width P Value MCP Width P Value PSP patients vs MSA-P patients Ͻ.001 .013 .001 .022 PSP patients vs PD patients Ͻ.001 Ͻ.001 Ͻ.001 Ͻ.001 PSP patients vs control participants Ͻ.001 Ͻ.001 Ͻ.001 Ͻ.001 MSA-P patients vs PD patients NS Ͻ.001 Ͻ.001 Ͻ.001 MSA-P patients vs control participants .019 Ͻ.001 Ͻ.001 Ͻ.001 PD patients vs control participants NS NS NS NS Possible PSP patients vs probable PSP patients .003 NS Ͻ.001 .018 Note.—P values were determined with Mann-Whitney U test, with Bonferroni correction. NS ϭ not significant. 218 Radiology: Volume 246: Number 1—January 2008 strated that 6% of patients with PSP had a P/M that overlapped with the P/M of con- trol participants, a finding that was consis- tent with our findings. Pathologic evidence has also dem- onstrated the atrophy of SCPs in pa- tients with PSP (1,17), whereas atrophy of MCPs has been found in patients with MSA (19). Results in recent MR imaging studies have confirmed these pathologic observations in both diseases. Atrophy of the SCPs has been shown on volumet- ric MR images in patients with PSP (15), and decreased width of MCPs re- cently has been demonstrated on mid- sagittal MR images in patients with MSA (20). On this basis, in our study we measured the width of both SCPs and MCPs on MR images and also investi- gated the MCP/SCP. Our data confirm pathologic findings showing that the SCP width was significantly smaller in Table 4 MR Parkinsonism Index for Differentiation of Patients with PSP from Patients with PD and MSA-P and Control Participants Cutoff and Statistical Values MR Parkinsonism Index Value MCP/SCP Value P/M Value PSP patients vs PD patients Cutoff value Ն13.55 Ն2.69 Ն4.88 Sensitivity (%) 100 78.8 90.9 Specificity (%) 100 88.9 93.5 PPV (%) 100 68.4 81.1 PSP patients vs MSA-P patients Cutoff value Ն12.85 Ն2.43 Ն4.62 Sensitivity (%) 100 93.9 97.0 Specificity (%) 100 89.5 94.7 PPV (%) 100 93.9 97.0 PSP patients vs control participants Cutoff value Ն13.58 Ն2.69 Ն4.65 Sensitivity (%) 100 78.8 97.0 Specificity (%) 100 88.0 94.0 PPV (%) 100 81.2 91.4 Note.—Optimal cutoff values were determined by using receiver operating characteristic curve analysis. NEURORADIOLOGY:MRParkinsonismIndexforDifferentiationofDiseases Quattroneetal
  10. 10. 45名の疾患が確定していないParkinsonismを呈する患者を対象. MRIにてMRPIを評価し, Cutoff ≥ 13.55を基準に2群に分類. その後2年間評価し, PSP診断基準をどの程度満たすかを評価. MRPI ≥13.55 を満たすのが15名, MRPI <13.55が30名. 28.4±11.7moフォローし, MRPI≥13.55群では11/15でPSPの診断基準を満たし, MRPI<13.55群でPSPの基準を満たしたのは0例. MRPI≥13.55は, 感度100%, 特異度90.3%でPSPを診断. MRPIのProspective cohort Neurology® 2011;77:1042–1047

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