Progressive supranuclear palsy
進行性核上麻痺

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

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.

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

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.

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.

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]

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

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

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