NPHの原因と症状

正常圧水頭症
Normal pressure hydrocephalus

正常圧水頭症
• Potentially reversible dementiaの原因の1つ.
• 歩行障害, 排尿障害, 認知症の3徴候を来すことで有名だが,
歩行障害が最も頻度が高く, 治療反応性が良好であり,
“Treatable gait disorder”の方が的を得ている. 認知症の無い例もあり.
• 頭蓋内圧も正常とは限らず, NPHよりは
“idiopathic adult hydrocephalus syndrome”と言う方が正しい.
• 発症率は5.5/100000, 有病率は21.9/100000.
有病率は加齢とともに上昇し,
50-59yrでは3.3/100000, 60-69yrでは49.3/100000,
70-79yrでは181.7/100000となる.
• 認知症患者の1-5%がNPHであるが,
その大半が発見が遅く, 治療しても改善は乏しい.
Curr Neurol Neurosci Rep. 2008 September ; 8(5): 371–376.
The Neurologist 2010;16: 238–248

NPHの症状
• 歩行障害
• 歩行失行, 不安定によるShort stepがあり,
Wide-based, 緩徐な動きとなる.
歩行はVPシャントにより改善しやすい兆候の1つ.
→ NPHは “Treatable dementia”ではなく “Treatable gait disorder”
• 上位ニューロンによる歩行障害パターン;
下肢筋力, 感覚(神経), 歩行サイクル(脳幹)は保たれているものの,
歩行運動のCoordinationが障害されているパターン.
高齢者の歩行障害の20%がこのパターン.
• 進行すると姿勢反射障害, 転倒の増加を認める.
• 40%で体肢の振戦を認める.
静止時振戦は少なく, 治療への反応性も少ない.
Curr Neurol Neurosci Rep. 2008 September ; 8(5): 371–376.The Neurologist 2010;16: 238–248

• 排尿障害
• 排尿筋の過活動が原因. 頻尿, 切迫性尿失禁が多い.
NPHの95%は排尿筋の過活動を認める.
歩行障害でトイレに行けないことも修飾因子となる.
• 前立腺肥大, 骨盤筋群萎縮の合併は多く,
その場合は手術治療による改善は期待できない.

• 認知症
• 前頭葉, 皮質下の障害が先ず出現.
(精神運動の緩徐化, 注意力障害, 空間認知, 決定能力の低下)
気分変調, 覚醒障害, 興味の減退も認められる.
これらはVPシャントにより改善する可能性がある.
• 脳血管障害を60%で合併する.
• 非対称性の静止時振戦, 鉛管様固縮, 視覚幻覚はDLBを示唆する.
DLBではNPHと同様の認知障害を認め得る.
• 失語, 失行, 失認はAlzheimer病, 脳血管性認知症, 前頭葉痴呆を示唆
• 歩行障害のない進行する認知症ではNPHより他の疾患を疑う.
• ADとNPHの合併はあり得るため, 判断が困難となる場合も.

• iNPHによる認知障害.
ADとの違い
patients with fairly advanced dementia may still respond posi-
tively to shunt placement (4).
When possible, quantifiable measures of cognitive perfor-
mance (neuropsychological tests) should be used. The impair-
ments detected should not be attributable to other conditions
such as neurodegenerative disorders, stroke, head trauma,
v
d
h
p
la
it
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ch
h
d
(2
of
IN
co
br
co
th
ities associated with INPH. An addi
seems to be depression is actually a
about by the psychomotor retardatio
monly seen in INPH. Whatever the
sentations in INPH are important to
may complicate clinical diagnosis an
May be made in the presence of a second systemic or brain disorder sufficient to produce dementia, which is
cause of the dementia
When a single, gradually progressive severe cognitive deficit is identified in the absence of other identifiable
TABLE 2.5. Comparison of cognitive deficits in Alzheimer’s disease and idiopathic normal-
pressure hydrocephalus
Cognitive skills Alzheimer’s disease Idiopathic normal-pressure hydrocephalus
Impaired Memory
Learning
Orientation
Attention concentration
Executive functions
Writing
Psychomotor slowing
Fine motor speed
Fine motor accuracy
Borderline impairment Motor and psychomotor skills
Visuospatial skills
Language
Reading
Auditory memory (immediate and delayed)
Attention concentration
Executive function
Behavioral or personality changes
Neurosurgery 57:S2-4-S2-16, 2005

NPHの機序
• 静脈のComplianceの低下により,
• arachnoid granulationからのCSF吸収が阻害されることが
原因として考えられている.
従って動脈硬化の関与も強く, 83%に高血圧合併.
また脳血管障害の合併例, 白質病変合併例が多い.
• 脳室拡大により脳室周囲の浮腫を生じ, 同部位の虚血を誘発.
白質病変の原因となり, 歩行障害, 認知障害, 排尿障害を来す.

NPH診断
• Probable iNPH
画像所見
脳室の拡大(Evan’s indes>0.3)
CSF経路の閉塞を認めない(画像的)
以下の1つ以上を満たす
1) 側脳室の下角の拡張(+),
桃体の萎縮の関連が無い
2) Callosal angleが≥40度
3) 小血管性病変に寄らない
脳室周囲の白質病変
4) MRIにて中脳水道, 第4脳室への
流出がある
病歴
緩徐進行性のOnset
>40yrでの発症
3-6mo以上の経過
二次性の原因となるイベント無し
(外傷, ICH, SAHなど)
進行性の病状
他に説明可能な疾患が除外
臨床所見
歩行障害を満たし,
認知障害, 排尿障害の何れかを満たす.
CSFの初圧が5-18cmH2O
認知障害は以下の2つ以上を満たす
a) 精神運動の緩徐化. 潜時の増加
b) 細かい運動の速度が低下
c) 細かい運動の正確性が低下
d) 注意障害
e) 最近の出来事の想起障害
f) 統合障害, マネージメント障害
g) 人格, 行動の変化
歩行障害とは, 以下の2つ以上を満たす
a) Step heightの低下
b) Step lengthの低下
c) Cadenceの低下
d) 体幹の動揺の増加
e) Wide-basedの歩行
f) 歩行時につま先が外側に向く
g) 後方突進減少
h) 180度の転換に2-3歩必要
i) tandem gait testで8歩中2回以上の補助
排尿障害は以下の1つ以上を満たす
a) 前立腺肥大, 解剖異常によらない症状
b) 持続的な排尿障害
c) 排尿, 排便障害
もしくは以下の2つ以上を満たす
a) 切迫性排尿障害
b) 12hrで6回以上の排尿
c) 夜間に2回以上の排尿

• Possible iNPH
• Unlikely iNPH
画像所見
脳室拡大はあるが, a) or b)を満たす
a) 拡大が説明可能な脳萎縮
b) 脳室
病歴
亜急性, 間欠性の経過
小児期以降に発症
<3moの経過
二次性の原因となるイベントあり
(外傷, ICH, SAHなど)
非進行性の経過
他に説明可能な疾患があり得る
臨床所見
歩行障害, バランス障害が無いが,
認知障害, 排尿障害を認める
歩行障害のみ or 認知症のみ
CSF初圧が不明
脳室拡大無し
ICP亢進あり, 乳頭浮腫あり
iNPHの古典的症状無し
他の疾患で説明可能

MRIによるCSF Spaceの評価
• 11名のVPシャントにて改善したiNPH患者と,
同年齢のAlzheimer病患者11名, 血管性痴呆11名で評価.
• T1-WIにおいて, 脳室, 基底槽, シルビウス裂,
シルビウス裂上のクモ膜下腔のSpaceを評価.
AJNR Am J Neuroradiol 19:1277–1284, August 1998
FIG 1. A–D, Illustrative sections of coro-
nal T1-weighted images (550/15/4) se-
lected from a patient with Alzheimer dis-
ease show the horizontal and vertical lines
that partition the CSF into the basal cis-
tern, sylvian fissure, and suprasylvian sub-
arachnoid space. The boundary of the CSF
is determined by density thresholding.
AJNR: 19, August 1998 IDIOPATHIC HYDROCEPHALUS 1279
the medial aspect of the temporal lobe, or the most lateral bank
of the orbital gyrus. The CSF volume in each compartment was
compared between the preoperative and postoperative MR
images of five patients whose postoperative images were ob-
tained at our hospital.
The MR data sets of coronal images were transmitted di-
rectly to a personal computer from the MR unit and analyzed
TABLE 2: Interrater
Lateral ventricle
Third ventricle
Aqueduct
AJNR: 19, August 1998 IDIOP
シルビウス裂基底槽
シルビウス裂シルビウス裂上のクモ膜下腔
基底槽

• 数字の羅列は, Spaceの拡張, 狭小化を表す.
[重度の拡張] / [軽度~中等度] / [正常]/ [狭小化]
• NPHでは, AD, VDと比較して側脳室, 第三脳室, 中脳水道,
第四脳室, シルビウス裂が著明に拡張.
• Superior medial space, 円蓋上部は正常 or 狭小化している.
基底槽はどれも有意差無し.
severe in the group with idiopathic NPH, as expected.
Dilatation of the aqueduct and the fourth ventricle
cistern or the sylvian fissure by narrow channels of
sulci (Fig 4).
FIG 2. Coronal T1-weighted MR images
(550/15/4) in a patient with idiopathic NPH
before (left) and after (right) ventriculoperi-
toneal shunt surgery. The CSF volume is
diminished both in the ventricles (by 28%)
and in the sylvian fissure (by 22%) after
surgery.
TABLE 3: Results of visual rating of CSF spaces
NPH* AD* VD* Among Groups
NPH vs
AD
NPH vs
VD
AD vs
VD
Lateral ventricle 9/2/0/0 0/6/5/0 1/7/3/0 Ͻ.001 Ͻ.001 .004 NS
Third ventricle 7/4/0/0 0/7/4/0 2/6/3/0 .002 .002 .04 NS
Aqueduct 4/6/1/0 0/1/10/0 0/2/9/0 Ͻ.001 Ͻ.001 .001 NS
Fourth ventricle 2/6/3/0 0/1/10/0 0/3/8/0 .005 .004 NS NS
Sylvian fissure 4/5/2/0 0/4/7/0 0/8/3/0 .02 .014 NS NS
Superior medial space 0/0/4/7 0/7/4/0 1/5/5/0 Ͻ.001 Ͻ.001 Ͻ.001 NS
Superior convexity space 0/0/5/6 0/7/4/0 2/5/4/0 Ͻ.001 .002 Ͻ.001 NS
Basal cistern 1/4/6/0 0/5/6/0 0/8/3/0 NS NA NA NA
Note.—NPH indicates idiopathic normal pressure hydrocephalus; AD, Alzheimer disease; VD, vascular dementia; NS, not significant; NA, not
applicable.
* Number of patients shown with severe dilatation, mild or moderate dilatation, normal, or decreased.
1280 KITAGAKI AJNR: 19, August 1998

• VolumetryによるCSF量の評価では,
• NPHでは側脳室のCSF量が著明に多く,
シルビウス裂上のクモ膜下腔のCSF量が著明に少ない.
• シルビウス裂は拡大しているが,
シルビウス裂と頭蓋骨間のSpaceは拡大していない画像となる.
tion detected in idiopathic NPH were corrected with
shunt surgery, indicating that these changes are re-
lated to NPH. Although an enlarged ventricular sys-
tem and decreased sulci are characteristic of commu-
nicating hydrocephalus, including NPH (6–9), the
finding of an enlargement of the sylvian fissure and
the basal cistern is a previously undescribed feature of
shunt-responsive idiopathic NPH.
Another hitherto unrecognized feature observed in
patients with idiopathic NPH is that a few sulci over
the convexity or medial surface of the hemisphere
were dilated in isolation. This isolated semiovoid sul-
cal dilatation appeared to be caused by the accumu-
lation of CSF in the subarachnoid space in a specific
sulcus. In other types of hydrocephalus, the pressure
from the ventricular system does not occur uniformly
over the brain surface, resulting in uneven dilatation
of the sulci. Although atrophy may predominate in
TABLE 4: Results of measurement of CSF volume
NPH AD VD Among Groups
NPH vs
AD
NPH vs
VD
AD vs
VD
Intracranial volume (mL) 1537 Ϯ 105 1497 Ϯ 161 1534 Ϯ 145 NS NA NA NA
Sylvian CSF (mL) 59.4 Ϯ 11.4 44.9 Ϯ 11.8 52.7 Ϯ 10.7 .019 .015 NS NS
Suprasylvian CSF (mL) 51.7 Ϯ 27.9 133.0 Ϯ 38.2 108.6 Ϯ 40.9 Ͻ.001 Ͻ.001 .003 NS
Ventricular CSF (mL) 142.9 Ϯ 34.4 57.7 Ϯ 26.1 65.3 Ϯ 20.9 Ͻ.001 Ͻ.001 Ͻ.001 NS
Basal CSF (mL) 40.0 Ϯ 6.2 38.6 Ϯ 6.6 43.2 Ϯ 8.0 NS NA NA NA
Percentage of sylvian CSF 3.9 Ϯ 0.9 3.0 Ϯ 0.7 3.4 Ϯ 0.6 .026 .02 NS NS
Percentage of suprasylvian CSF 3.4 Ϯ 1.8 8.9 Ϯ 2.5 7.0 Ϯ 2.2 Ͻ.001 Ͻ.001 .002 NS
Percentage of ventricular CSF 9.3 Ϯ 2.1 3.8 Ϯ 1.5 4.3 Ϯ 1.4 Ͻ.001 Ͻ.001 Ͻ.001 NS
Percentage of basal CSF 2.6 Ϯ 0.5 2.6 Ϯ 0.5 2.8 Ϯ 0.6 NS NA NA NA
Note.—NPH indicates idiopathic normal pressure hydrocephalus; AD, Alzheimer disease; VD, vascular dementia; NS, not significant; NA, not
applicable.
1282 KITAGAKI AJNR: 19, August 1998

DESH
• Disproportinately Enlarged Subarachnoid-space Hydrocephalus
• iNPHに典型的な,
円蓋部の狭小化, シルビウス裂の拡大, 脳室拡大をDESHと呼ぶ.
• iNPHの90%がDESHを満たすが, 10%はnon-DESHとなる.
• 実際は画像+症状と, タッピングテストへの反応性で診断.
Cerebrospinal Fluid Research 2010, 7:18

治療
• Ventriculoperitoneal, ventriculopleural, ventriculoatrial shunt
• 約60%で効果を認める.
• Meta-analysisではシャントによる合併症率は38%
(死亡, 感染, 痙攣, シャント不全, 硬膜下出血)
• 追加手術を必要とする例は22%. 死亡, 恒久的神経障害残存は6%
• 10年間のフォローでは, 死亡1%, 硬膜下血腫3%,
感染12%, シャント感染6.7%, シャントrevision 33%.
• VPSの有効性
• 高齢のみで他に手術のリスクが無い場合は,
VPSをためらう必要は無し. 治療効果は期待できる.
ただし, 3兆候がっている場合は高齢ほど予後は悪い.

• VPシャントの適応
• CSF圧高値の場合は二次性のNPHを精査する
• 40ml~50mlのTapping testで反応あれば
シャントにより改善する可能性がある.
• ELD(external lumbar drainage)は
Tapping testで反応無い症例の評価に有用
• MRI CSF ﬂow評価には明確な基準, 有効性が証明されていない.

• CSF tapping test
• >30ml(50ml)のCSFを採取し, その前後(1-2日後まで)の症状を評価.
iNPHの診断のみならず, VPSの有効性の判断にも使用可能.
• Cine phase-contrast MRI
• 収縮期, 拡張期でcerebral aqueductのCSF Flowを評価.
Stroke volume>42µLはVPSへの反応良好を示唆する.(12/12 vs 3/6)

• SINPHONI trial; 日本国内のprospective study
• 60-85yrで歩行障害, 認知障害, 排尿障害のいずれか1つ以上あり,
MRIにて脳室の拡大, 円蓋部狭小化, 中央くも膜下腔の狭小化(+)を
満たす100名でVPシャントを施行.
• 平均年齢は74.5(5.1)yr, 58名が男性.
歩行障害 91%, 認知障害 80%, 排尿障害 60%.
古典的三徴を認めたのは51%のみ.
CSF圧は11.9(3.4)cmH2O
Evans indexは35.6(4.0)%
Methods
Study design
The study was a multicenter prospective cohort study
conducted in compliance with the Guidelines for Good
Clinical Practice and the Declaration of Helsinki (2002)
of the World Medical Association. The study protocol
was approved by the institutional review board at each
site, and all patients (or their representatives when
content (protein ≤ 50 mg/dl and cell count ≤
pressure (≤ 20 cmH2O). Exclusion criteria w
sence of musculoskeletal, cardiopulmonary,
tic, or mental disorders that would make it
evaluate changes of symptoms, (2) obstacles
follow-up, and (3) hemorrhagic diathesis or
lant medication. For the evaluation of the M
index, size of the Sylvian fissures rated acco
protocol of Kitagaki et al. [10], presence or
Figure 1 Typical iNPH findings on MRI. Illustrative coronal sections of coronal T1-weighted images selected from an included pat
enlarged ventricles (*), tight high-convexity and medial surface subarachnoid spaces (oval ring), and expanded Sylvian fissures (arrow• Evans indexの分布
on the TUG. When one point or more decrement on
the total score of the iNPHGS is regarded as clinical
improvement, benefits were noted in 77% of the subjects
at one year after surgery. Shunt responder (improve-
ment ≥ 1 on mRS at any evaluation point in one year)
was noted in 80%, 95% CI: 71.0-86.7% (Figure 6). When
using the iNPHGS as a measure, the response to the
surgery was detected in 89% of the subjects.
Adverse events
Serious adverse events (SAE) were noted in 15 patients
(Figure 6): death occurred in two patients (lung cancer
and pneumonia). Outcome at one year was favourable
in 4 patients and unfavourable in 11 patients (including
the two deaths). Three SAEs were directly related to
ventricular shunt tube obstruction requirin
addition, 21 non-serious shunt-related ad
were recorded in 20 patients: asymptoma
effusion on brain imaging in 13 patients
headache in 8 patients, which were succ
trolled in all cases by adjustment of valve p
Discussion
The present study examined both the usef
MRI-based diagnostic scheme and the one
cial effect of shunt surgery for patients wit
diagnosis of iNPH is established in terms o
surgery, and the efficacy of surgery depend
tic accuracy. Therefore, there is an interac
the accuracy of the diagnostic scheme and
of the treatment. Nevertheless, we achieved
ment rate of 69.0% on daily life activity, wh
that all the procedures, including diagnos
ment, yield reasonable net benefits. Furt
proved that the diagnostic scheme has a
predictive value, as the percentage of subje
found at one evaluation point to have resp
VP shunt was 80.0% for the whole group
cates that MRI-based diagnosis is useful fo
sis of iNPH.
Assessment of the outcome in iNPH p
important issue; activity of daily life wo
Table 2 Combination of symptoms
Combination of symptoms* No. of patients
Triad 51
Gait and cognitive 23
Gait and urinary 5
Cognitive and urinary 3
Gait only 12
Cognitive only 3
Urinary only 1
Subjective symptoms only 2
Table 1 Background characteristics for patients in study
Age (years) 74.5 ± 5.1
Sex (male) 58%
Education (years) 10.2 ± 2.9
Systolic pressure (mmHg) 131.0 ± 14.6
Diastolic pressure (mmHg) 75.7 ± 8.9
History of hypertension 60%
History of diabetes 20%
History of a lipid disorder 31%
Smoking status
Currently 10%
Previously 37%
Medications (% present)
L-dopa/dopamine agonist 10%
Hashimoto et al. Cerebrospinal Fluid Research 2010, 7:18
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Page 6 of 11

• VPシャントに反応したのは80%.
• 予後良好であったのは69%[59.4-77.2].
• 合併症は15%で認められた. 死亡2名(肺癌, 肺炎)
VPSに直接関係する合併症は3名のみ.
(硬膜下血腫, 腸孔, チューブ閉塞)
study, clinical improvement was defined as at least a one
level improvement on mRS. The mRS is the most popu-
lar assessment of global outcome in stroke [16], and has
treated 101 patients with iNPH with VP shunt by using
fixed pressure valves, and yielded a one-year improve-
ment rate of 59% based on mRS [24]. The group reported
Figure 7 Bar charts of patients’ functional status based on the modified Rankin scale (mRS). A: Distribution at baseline and one year.
B: Change between baseline and one year.
Hashimoto et al. Cerebrospinal Fluid Research 2010, 7:18
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Page 8 of 11

• 治療反応性
neurological diseases [21-23], including iNPH [24,25].
As the grading definitions of the mRS are very broad
classifications of disability, only sizable changes can be
detected [22]. Moreover, inter-rater reliability may be an
important source of error with the mRS. However, in
this study, improvements were detected in a large pro-
portion of the subjects, suggesting a significant treat-
ment effect. The improvements were also confirmed on
all the other scales used. In particular, the iNPHGS,
which is a valid and reliable scale specific for iNPH [14],
provided a very sensitive means of detecting change;
this scale detected improvements in 77.0%. The timed
“Up & Go” test also detected improvements even in the
subgroup with unfavorable outcome, where no improve-
ment or deterioration was recorded on the less sensitive
mRS. Therefore, if the low sensitivity of the mRS is
taken into consideration, the outcome in this study is
acceptable.
Serious adverse events occurred in 15 patients, and all
but three of these were unrelated to the operation or VP
shunt. Considering the subjects’ mean age of 75 years,
vascular events, malignancies, infections, and fractures
were not uncommon. Outcomes for those who experi-
enced an SAE were generally unfavorable, as would be
expected. In addition, asymptomatic subdural effusion (n
= 13) and orthostatic headache (n = 8) were reported as
non-serious shunt-related adverse events. These were
controlled well by adjustment of valve pressure [24].
Although a considerable number of retrospective case
series have been published [26-28], prospective studies
using standardized validated outcome measures, which
are comparable to the present study, are very scarce. The
Dutch NPH study group, in their prospective study,
transient and persistent subdural effusion in 53% of
Table 3 Changes of outcome measures with each
outcome group.
Baseline 12 months p value*
INPHGS gait score
All patients 2 (2.3-2.6) 1 (1.2-1.7) < 0.001
Favorable outcome 2 (2.3-2.6) 1 (0.8-1.3) < 0.001
Unfavorable outcome 2 (2.1-2.7) 2 (1.9-2.8) ns
iNPHGS cognitive score
All patients 2 (2.1-2.4) 1 (1.3-1.7) < 0.001
iNPHGS urinary score
All patients 2 (1.7-2.2) 1 (0.8-1.3) < 0.001
iNPHGS total score
All patients 6 (6.1-7.1) 4 (3.4-4.6) < 0.001
Timed “up & go” test (seconds)
All patients 20.5 (16-30) 14 (11-20) < 0.001
Favorable outcome 20 (16.5-28) 13 (10-17) < 0.001
Unfavorable outcome 22 (15-41) 20 (13-33) 0.004
MMSE
All patients 23 (16.3-26) 25 (20.3-28) < 0.001
Favorable outcome 23 (15.5-26) 25 (21.5-28) < 0.001
Unfavorable outcome 23 (17-25) 24 (16-27) ns
Data are median (75th percentile).
*All p values were obtained using Wilcoxon test. ns: not significant.
iNPHGS: Idiopathic Normal-Pressure Hydrocephalus Grading Scale, MMSE:Mini-
Mental State Examination.

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