多系統萎縮症
Multiple system atrophy (MSA)

MSA
孤発性, 急速進行性の神経変性疾患
自律神経障害, パーキンソン症候群, 小脳失調を3徴とし,
どれが前面にでるかでMSA-P, Cと表現される.
錐体路障害も認められる.
組織学的には, 基底核, 小脳, 橋, オリーブ下核, 脊髄の
グリオーシスを伴う神経脱落を認める.
発症率は0.6/100000-yr, >50yrでは3/100000-yr.
有病率は1.9-4.9/100000.
平均発症年齢は60y[34-83], 男女差は無し.
平均予命は発症から7-9yr程度と予後は悪い.
Lancet Neurol 2009; 8: 1172–78

MSA-Pが58-60%を占める
MSA-Cが13-42%, 残りは混合性運動障害や分類不能type.
日本国内ではMSA-Cが最多(83.8%)となり,
MSA-Pは16.2%と少ない.
MSA-PはPDよりも進行が早い.
晩期では運動障害も合併.
MRI-DWIではびまん性に被殻のHigh-intensityを認め,
徐々に全皮質に進展する.
早期に自律神経障害を認める場合は予後不良因子.
Lancet Neurol 2009; 8: 1172–78
J Neurol Sci. 2006 Nov 15;249(2):115-21

MSAの臨床症状は,自律神経障害, 膀胱直腸障害,
小脳失調, パーキンソン症状, 錐体路徴候の組み合わせ.
European MSA registryからの報告では
平均年齢57.8歳, 平均罹患期間5.8yr,
MSA-P 68.2%, MSA-C 31.8%
Lancet Neurol 2009; 8: 1172–78
自律神経障害 99% MSA-P MSA-C
排尿障害 83% パーキンソン症状 87%(MSA-C 61%) 小脳失調 64%(MSA-P 47%)
切迫性尿失禁 73% 固縮 93% 歩行失調 86%
残尿 48% 姿勢反射障害 89% 四肢失調 78%
勃起障害 84% 姿勢時振戦 54% 失調性構音障害 69%
起立時調節障害 75% 安静時振戦 33%
ΔBP 20/10 59% Freezing of gait 38%
ΔBP 30/15 46%
起立時失神 19%
慢性便秘症 33%
錐体路症状 神経精神症状
Babinski陽性 28% うつ病 41%
DTR亢進 43% 幻覚 5.5%
認知症 4.5%
不眠 19%
日中の傾眠 17%
Restless leg 10%

MSAの診断Criteria
Lancet Neurol 2009; 8: 1172–78
Probable MSA; 孤発性, 進行性, >30yの発症で以下を満たす
膀胱直腸障害を伴う自律神経障害を認める
重度の起立性低血圧(ΔBP 30/15)を認め,
Levodopa不応性のパーキンソン症状, もしくは
小脳症状(歩行失調, 構音障害, 四肢失調, 小脳眼球運動障害)
Possible MSA; 孤発性, 進行性, >30y発症で以下を満たす
パーキンソン症状 or 小脳失調
自律神経障害を示唆する所見を1つ以上認める
(説明困難な排尿障害, 残尿, 勃起障害, 重度の起立性低血圧)
以下から1つ以上の特徴を認める
Possible MSA-P
急速進行性のパーキンソン症状
レボドパへの反応性が乏しい
運動障害発症から3年以内に姿勢反射障害を認める
歩行失調, 小脳失調
運動障害から5年以内に嚥下障害を認める
MRIにて被殻, 中小脳脚, 橋, 小脳の萎縮を認める
FDG-PETで線条体, 脳幹, 小脳のHypometabolism
Possible MSA-C
パーキンソン症状を認める
MRIにて被殻, 中小脳脚, 橋の萎縮あり
FDG-PETで線条体のHypometabolismあり
SPECT, PETでpresynaptic nigrostriatal
dopaminergic denervationを認める

MSAを示唆する所見, 示唆しない所見
MSAを示唆する所見
MSAを示唆しない所見
口顔面のジストニア Inspiratory sighs 手足が冷たい
不均衡なAntecollis 重度のジストニア 病的な笑い, 泣き
前屈症(重度の脊椎の前屈)
± Pisa syndrome(重度の脊椎の側屈)
重度の構音障害
姿勢時, 運動時の衝動的な
ミオクローヌス様振戦
手, 足関節の拘縮 いびきの出現, 増悪
古典的なPill-rolling振戦 失調, パーキンソン症状の家族歴 MSを示唆する白質病変
明らかな神経障害を認める 認知症あり 薬剤によらない幻覚
75歳以上の発症

PD, PSP, MSAの進行
PD発症期間は重なるが, 比較的若い年齢で発症.
急速進行し, 診断から10年も満たずに死亡.
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pathological grading system was proposed in 2005 to
quantify GCI density and neuronal loss associated with
striatonigral degeneration and olivopontocerebellar
ataxia.31
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GCIs is not yet understood, the crucial role of
50 60
Age (years)
PD
PSP
MSA
70
Dx
Dx
F C
C
C
RFDx
F
RD
WUD
UW
R
80
Figure 1: Milestones of disease advancement and total disease course
The green rectangles indicate disease duration, commencing with the timepoint of first symptoms.The vertical
lines denote time of clinical diagnosis of a parkinsonian or a cerebellar syndrome (Dx) and time of documentation
of milestones of disease advancement. Reproduced from O’Sullivan and colleagues,21
with permission from Oxford
University Press. C=cognitive disability. D=dysarthria or dysphagia. Dx=clinical diagnosis. F=frequent falls.
MSA=multiple system atrophy. PD=Parkinson’s disease. PSP=progressive supranuclear palsy. R=residential care.
U=urinary catheter.W=wheelchair dependent.
Lancet Neurol 2009; 8: 1172–78
C; cognitive disability, D; dysarthria, Dysphagia F; Frequent falls, R; Residential care,
U; urinary catheter,W; wheelchair dependent

認知症合併率
MSAでは認知機能低下は20%程度のみ.
PSPでは59%であり, 認知症合併例では
他のパーキンソニズムをきたす疾患を考慮すべきといえる.
125 or MMSE score 24. The MMSE score was used for tenta-
tive classification only when a DRS score was not available.
Cognitive status was not assessed or was not assessable in three
patients, all with a clinical diagnosis of progressive supranuclear
palsy that was confirmed on pathological examination.
The majority (76.7%) of the progressive supranuclear palsy
group coming to post-mortem were cognitively impaired at the
time of the initial assessment, and diagnosis was confirmed in
89.1%. In four of the impaired patients, significant coincident
Alzheimer pathology (Braak stage 4–5) was reported, although
no patient received a primary diagnosis of Alzheimer’s disease.
Cases where an alternative diagnosis was made included cortico-
basal degeneration, Lewy body disease and amyotrophic lateral
sclerosis, plus one impaired patient with an initial clinical diagnosis
of progressive supranuclear palsy received a final diagnosis of
multiple system atrophy. Diagnostic accuracy was 85.7% in the
Table 4 Percentage of cognitively impaired (DRS 125) patients in multiple system atrophy and progressive supranuclear
palsy groups according to Clinician Global Impression disease severity and disease duration at assessment
Multiple system atrophy Progressive supranuclear palsy
Disease duration Disease duration
CGI of disease severity 54 years 4 years Total 54 years 4 years Total
3–6 15% (137) 24% (197) 20% (334) 61% (138) 63% (123) 62% (261)
1–2 22% (23) 0 (15) 13% (38) 50% (40) 30% (10) 46% (50)
Total 16% (160) 23% (212) 20% (372) 58% (178) 61% (133) 59% (311)
Numbers in parentheses show the total number of patients in the cell regardless of impairment and the percentages are depicted outside the parentheses.
CGI = Clinician Global Impression.
Figure 4 Percentage of multiple system atrophy (MSA) and
progressive supranuclear palsy (PSP) patients with cognitive
impairment (DRS total score 125) at different disease durations.
Data table shows total n per duration year for each group.
Brain 2010: 133; 2382–2393

123I-MIBGシンチ
123I-MIBG心筋シンチはPD, DLBで取り込み低下する.
多系統萎縮症では21.4%で取り込み低下を認めるのみ.
PD, DLBとの鑑別に有用となる.
特にHeart/Mediastinum ratio(H/M)で評価する方がよく,
多系統萎縮症では
早期H/M(eH/M) 2.57±0.49, 晩期H/M(dH/M) 2.91±0.53
SLEEP 2008;31(5):717-723.
J Neurol Neurosurg Psychiatry 2005;76:249-51
Table 1
IRBD PD DLB MSA PSP Control P
† §¶ ‡¶ ‡¶
‡¶ ‡¶ ‡¶
-
SD
†
‡ §
¶
Table 1
IRBD PD DLB MSA PSP Control
† §¶ ‡¶ ‡¶
‡¶ ‡¶ ‡¶
SD
†
‡ §
¶
IRBD; idiopathic REM sleep behavior disorder

MSAのMRI所見
MSA 44名, PD 47名, Control 45名のMRIを
2名のBlindされた専門医が読影.
感度は低いが, 特異性が高い所見としては
橋の十字とHyperintense rim,
被殻が基底核と被殻して低信号となる所見.
J Neurol Neurosurg Psychiatry 1998;65:65–71
IPD(47) Control(45) MSA(44)
橋の十字サイン 0 0.5(1.1%) 15(34.1%)
Hyperintense rim 0 0 15(34.1%)
Isointense rim 10(21.3%) 15.5(34.4%) 11.5(26.1%)
被殻/基底核がIso 15.5(33.0%) 12(26.7%) 18(41.0%)
被殻/基底核がHypo 1(2.1%) 0.5(1.1%) 5(11.4%)
被殻が明らかにHigh 0 0 7(16.0%)
被殻が明らかにHypo 21(44.7%) 26(57.8%) 28(63.6%)
被殻萎縮 15(31.9%) 16(35.6%) 18.5(42.0%)
Hyperintense rim

PD 21名, MSA-C 11名, MSA-P 8名, PSP 20名で評価
T1 矢状断で中脳(Ams), 橋面積(Apn)を評価(A)
(橋のNotchと四丘の下部を結ぶ線と平行の下端の線)
T2 水平断で上小脳脚(SCP), 中小脳脚直径(MCP)を評価(B, C)
Arq Neuropsiquiatr 2010;68(3):333-338
Arq Neuropsiquiatr 2010;68(3)
omes: MRI morphometry
Table 1. Comparisons among measurements obtained**.
Parkinson PSP MSA-c MSA-p
Apn
(mm2
)
556.6
(472.9-622.2)
443.4
(321.1-508.4)
303.4
(235.4-408.6)
331.6
(195.1-468.2)
Ams
(mm2
)
154.8
(129.3-190.9)
82.1
(52.5-113.4)
151.4
(126.7-166.2)
117.8
(88.3-154.8)
MCP
(mm)
17.1
(14.8-19.0)
14.5
(10.4-16.9)
9.7
(7.2-12.5)
11.7
(6.5-19.3)
SCP
(mm)
3.7
(3.1-4.2)
2.0
(1.5-2.9)
3.3
(2.5-3.7)
3.3
(1.5-4.4)
334
used clinically to distinguish among PD, PSP, MSA-c and
MSA-p with good sensitivity, specificity and accuracy.
The aim of this study was to evaluate the diagnostic val-
ue of structural anatomic changes identified by MRI and
propose MRI-based criteria to help the clinician to rec-
ognize these parkinsonian syndromes.
METHOD
Patients
This is a cross-sectional study of sequential patients
was used for measurements of the midbrain a
and pons area (Apn)12-14
(Fig 1). These areas wer
according to the following parameters: two str
were drawn. The first line was drawn so as to pa
the superior pontine notch and the inferior e
quadrigeminal plate. The second line was dra
lel to the first line so as to pass through the in
tine notch. The area of the midbrain was trace
the delta-shaped part above the first line. The
pons was traced as the area between the vent
Fig 1. Measurements of midbrain and pons areas (Fig 1A, sagittal T1-weighted); measurement of SCP (Fig 1B,
axial T2-weighted); measure of MCP (Fig 1C, axial T2-weighted).

PD, MSA, PSPの鑑別において,
Arq Neuropsiquiatr 2010;68(3):333-338
from cases with MSA-c and MSA-p did not differ. How-
ever, values of Ams was significantly different (p0.05).
the diagnosis (p0.01). In MSA-c cases,
and MCP measures were significantly diff
MSA-c: multiple system atrophy with cerebellar signs; MSA-p: multiple system atrophy with parkinsonian features;
PSP: progressive supranuclear palsy; Ams: midbrain area Apn: pons area; MCP: middle cerebellar peduncle; SCP:
superior cerebellar peduncle; NS: non-significant.
Table 3. Cut off, sensitivity, specificity, accuracy, positive and negative predictive values regarding
Parkinson s disease, PSP and MSA-c.
Cut off Sensitivity Specificity Accuracy PPV PNV
Parkinson
Apn
Ams
MCP
SCP
477
133
15
3.3
80.0%
65.5%
71.4%
65.5%
97.1%
93.5%
96.9%
93.5%
90.0%
80.0%
85.0%
80.0%
95.2%
90.0%
95.2%
90.5%
87.2%
74.4%
79.5%
74.4%
PSP
Apn*
Ams
MCP*
SCP
‒
105
‒
3
‒
95.0%
‒
80.0%
‒
97.5%
‒
100%
‒
96.7%
‒
91.7%
‒
95.0%
‒
100%
‒
97.5%
‒
87.5%
MSA-c
Apn
Ams
MCP
SCP*
105
315
12
‒
77.5%
66.7%
66.7%
‒
100%
93.8%
97.8%
‒
88.3%
51.7%
90.0%
‒
100%
72.7%
90.9%
‒
80.8%
91.8%
89.8%
‒
MSA-c: multiple system atrophy with cerebellar signs; PSP: progressive supranuclear palsy; Ams: midbrain area;
Apn: pons area; MCP: middle cerebellar peduncle; SCP: superior cerebellar peduncle; *non-significant (p0.05);
PPV: predictive positive values; PNV: predictive negative values.

日本国内のMSA患者のフォロー
230名のMSA患者のフォロー
MSA-C 155名(67.4%), MSA-P 75名(32.6%)
平均年齢は55.4±8.3y.
初発症状は自律神経症状が27.8%, 運動症状が72.2%.
発症からの期間と運動障害 or 自律神経障害合併頻度.
(Aが全体, Bはtype別; 太線 MSA-P, 薄線 MSA-C)
Brain 2002;125:1070-83

A; 歩行に補助が必要となるまでの期間
B; 車いすが必要となるまでの期間
C; 寝たきりになるまでの期間
D; 死亡までの期間
Brain 2002;125:1070-83

発症∼運動障害と自律神経障害併発までの期間別で
分けたOutcomeまでの期間
□ 1yr, △ 2-3年, ○ 3年以上.
基本的に運動障害と自律神経症状が うまでの期間が
長いほど, ADLはより長く保たれる傾向にある.
Brain 2002;125:1070-83

MSA-P(△), MSA-C(○) 別のADL outcome
Brain 2002;125:1070-83

Superficial Siderosis
脳表ヘモジデリン沈着症.
大脳, 脊髄の軟膜下のヘモジデリン沈着を認める病態.
主に画像所見から診断されることが多い.
症状は脊髄小脳変性症(MSA-C)と同様の所見であり,
MSA-Cよりも緩徐進行となる.
画像も脳幹の萎縮は乏しく, ヘモジデリン沈着と
小脳萎縮を特徴とする. ヘモジデリンはT2*で明瞭に分かる
症状の報告; (http://www.treatneuro.com/archives/1365)
小脳失調 81% 複視 4%
感音性難聴 81% 直腸障害 3%
ミエロパチー 53% 味覚障害 2%
排尿障害 14% 脳神経麻痺 2%
嗅覚障害 14% その他 その他はてんかん, 認知機能障害など
AJNR 2012;31:5-14

T2-WIによる沈着所見
JはT1, 小脳萎縮所見
AJNR 2012;31:5-14

Fig 3. A and B, Sagittal (A) and axial (B) T2-weighted spinal cord MR images show hemosiderin deposition along (A) and around (B) the cord surface. Note associated severe cord atrophy
(A) (dotted arrow). C and D, Axial T2-weighted MR images at the level of the cauda equina from patients with SS show peripheralization (C) and clumping (D) of the nerve roots due to
arachnoiditis. E, An axial cut at the lumbar levels on a CT myelogram from a patient with SS shows clumping of nerve roots of the cauda equina due to arachnoiditis. F, T2-weighted sagittal
MR image of the lumbosacral area from a patient with SS shows a lesion that was suspected of being a possible source of the chronic bleeding. A biopsy was performed, and blood products
and fibrous tissue were detected. C and E reprinted with permission from Kumar N. Superficial siderosis: associations and therapeutic implications. Arch Neurol 2007;64:491–96 (Copyright
2007, American Medical Association).
脊髄へのヘモジデリン沈着
AJNR 2012;31:5-14
脳表面へのヘモジデリン沈着所見は≥60yの一般人口の0.7%で認める所見.
原因は脳出血やSAH, アミロイドアンギオパチー, アルツハイマーなど
言われているが, ハッキリとは判明していないのが現状.
Neurology® 2009;73:202–205