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正常圧水頭症

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    正常圧水頭症 正常圧水頭症 Presentation Transcript

    • 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.Curr Neurol Neurosci Rep. 2008 September ; 8(5): 371–376.The Neurologist 2010;16: 238–248
    • • 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.Curr Neurol Neurosci Rep. 2008 September ; 8(5): 371–376.The Neurologist 2010;16: 238–248
    • • 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 conditionssuch as neurodegenerative disorders, stroke, head trauma,vdhplaitcochhd(2ofINcobrcothities associated with INPH. An addiseems to be depression is actually aabout by the psychomotor retardatiomonly seen in INPH. Whatever thesentations in INPH are important tomay complicate clinical diagnosis anMay be made in the presence of a second systemic or brain disorder sufficient to produce dementia, which iscause of the dementiaWhen a single, gradually progressive severe cognitive deficit is identified in the absence of other identifiableTABLE 2.5. Comparison of cognitive deficits in Alzheimer’s disease and idiopathic normal-pressure hydrocephalusCognitive skills Alzheimer’s disease Idiopathic normal-pressure hydrocephalusImpaired MemoryLearningOrientationAttention concentrationExecutive functionsWritingPsychomotor slowingFine motor speedFine motor accuracyBorderline impairment Motor and psychomotor skillsVisuospatial skillsLanguageReadingAuditory memory (immediate and delayed)Attention concentrationExecutive functionBehavioral or personality changesNeurosurgery 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.Curr Neurol Neurosci Rep. 2008 September ; 8(5): 371–376.
    • NPH診断• Probable iNPHNeurosurgery 57:S2-4-S2-16, 2005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 iNPHNeurosurgery 57:S2-4-S2-16, 2005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 1998FIG 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 linesthat partition the CSF into the basal cis-tern, sylvian fissure, and suprasylvian sub-arachnoid space. The boundary of the CSFis determined by density thresholding.AJNR: 19, August 1998 IDIOPATHIC HYDROCEPHALUS 1279the medial aspect of the temporal lobe, or the most lateral bankof the orbital gyrus. The CSF volume in each compartment wascompared between the preoperative and postoperative MRimages 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 analyzedTABLE 2: InterraterLateral ventricleThird ventricleAqueductAJNR: 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 ventriclecistern or the sylvian fissure by narrow channels ofsulci (Fig 4).FIG 2. Coronal T1-weighted MR images(550/15/4) in a patient with idiopathic NPHbefore (left) and after (right) ventriculoperi-toneal shunt surgery. The CSF volume isdiminished both in the ventricles (by 28%)and in the sylvian fissure (by 22%) aftersurgery.TABLE 3: Results of visual rating of CSF spacesNPH* AD* VD* Among GroupsNPH vsADNPH vsVDAD vsVDLateral ventricle 9/2/0/0 0/6/5/0 1/7/3/0 Ͻ.001 Ͻ.001 .004 NSThird ventricle 7/4/0/0 0/7/4/0 2/6/3/0 .002 .002 .04 NSAqueduct 4/6/1/0 0/1/10/0 0/2/9/0 Ͻ.001 Ͻ.001 .001 NSFourth ventricle 2/6/3/0 0/1/10/0 0/3/8/0 .005 .004 NS NSSylvian fissure 4/5/2/0 0/4/7/0 0/8/3/0 .02 .014 NS NSSuperior medial space 0/0/4/7 0/7/4/0 1/5/5/0 Ͻ.001 Ͻ.001 Ͻ.001 NSSuperior convexity space 0/0/5/6 0/7/4/0 2/5/4/0 Ͻ.001 .002 Ͻ.001 NSBasal cistern 1/4/6/0 0/5/6/0 0/8/3/0 NS NA NA NANote.—NPH indicates idiopathic normal pressure hydrocephalus; AD, Alzheimer disease; VD, vascular dementia; NS, not significant; NA, notapplicable.* Number of patients shown with severe dilatation, mild or moderate dilatation, normal, or decreased.1280 KITAGAKI AJNR: 19, August 1998AJNR Am J Neuroradiol 19:1277–1284, 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 withshunt 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), thefinding of an enlargement of the sylvian fissure andthe basal cistern is a previously undescribed feature ofshunt-responsive idiopathic NPH.Another hitherto unrecognized feature observed inpatients with idiopathic NPH is that a few sulci overthe convexity or medial surface of the hemispherewere 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 specificsulcus. In other types of hydrocephalus, the pressurefrom the ventricular system does not occur uniformlyover the brain surface, resulting in uneven dilatationof the sulci. Although atrophy may predominate inTABLE 4: Results of measurement of CSF volumeNPH AD VD Among GroupsNPH vsADNPH vsVDAD vsVDIntracranial volume (mL) 1537 Ϯ 105 1497 Ϯ 161 1534 Ϯ 145 NS NA NA NASylvian CSF (mL) 59.4 Ϯ 11.4 44.9 Ϯ 11.8 52.7 Ϯ 10.7 .019 .015 NS NSSuprasylvian CSF (mL) 51.7 Ϯ 27.9 133.0 Ϯ 38.2 108.6 Ϯ 40.9 Ͻ.001 Ͻ.001 .003 NSVentricular CSF (mL) 142.9 Ϯ 34.4 57.7 Ϯ 26.1 65.3 Ϯ 20.9 Ͻ.001 Ͻ.001 Ͻ.001 NSBasal CSF (mL) 40.0 Ϯ 6.2 38.6 Ϯ 6.6 43.2 Ϯ 8.0 NS NA NA NAPercentage of sylvian CSF 3.9 Ϯ 0.9 3.0 Ϯ 0.7 3.4 Ϯ 0.6 .026 .02 NS NSPercentage of suprasylvian CSF 3.4 Ϯ 1.8 8.9 Ϯ 2.5 7.0 Ϯ 2.2 Ͻ.001 Ͻ.001 .002 NSPercentage of ventricular CSF 9.3 Ϯ 2.1 3.8 Ϯ 1.5 4.3 Ϯ 1.4 Ͻ.001 Ͻ.001 Ͻ.001 NSPercentage of basal CSF 2.6 Ϯ 0.5 2.6 Ϯ 0.5 2.8 Ϯ 0.6 NS NA NA NANote.—NPH indicates idiopathic normal pressure hydrocephalus; AD, Alzheimer disease; VD, vascular dementia; NS, not significant; NA, notapplicable.1282 KITAGAKI AJNR: 19, August 1998AJNR Am J Neuroradiol 19:1277–1284, 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.Curr Neurol Neurosci Rep. 2008 September ; 8(5): 371–376.
    • • 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.Curr Neurol Neurosci Rep. 2008 September ; 8(5): 371–376.
    • • 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)Curr Neurol Neurosci Rep. 2008 September ; 8(5): 371–376.
    • • 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)cmH2OEvans indexは35.6(4.0)%Cerebrospinal Fluid Research 2010, 7:18MethodsStudy designThe study was a multicenter prospective cohort studyconducted in compliance with the Guidelines for GoodClinical Practice and the Declaration of Helsinki (2002)of the World Medical Association. The study protocolwas approved by the institutional review board at eachsite, and all patients (or their representatives whencontent (protein ≤ 50 mg/dl and cell count ≤pressure (≤ 20 cmH2O). Exclusion criteria wsence of musculoskeletal, cardiopulmonary,tic, or mental disorders that would make itevaluate changes of symptoms, (2) obstaclesfollow-up, and (3) hemorrhagic diathesis orlant medication. For the evaluation of the Mindex, size of the Sylvian fissures rated accoprotocol of Kitagaki et al. [10], presence orFigure 1 Typical iNPH findings on MRI. Illustrative coronal sections of coronal T1-weighted images selected from an included patenlarged 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 onthe total score of the iNPHGS is regarded as clinicalimprovement, benefits were noted in 77% of the subjectsat 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). Whenusing the iNPHGS as a measure, the response to thesurgery was detected in 89% of the subjects.Adverse eventsSerious adverse events (SAE) were noted in 15 patients(Figure 6): death occurred in two patients (lung cancerand pneumonia). Outcome at one year was favourablein 4 patients and unfavourable in 11 patients (includingthe two deaths). Three SAEs were directly related toventricular shunt tube obstruction requirinaddition, 21 non-serious shunt-related adwere recorded in 20 patients: asymptomaeffusion on brain imaging in 13 patientsheadache in 8 patients, which were succtrolled in all cases by adjustment of valve pDiscussionThe present study examined both the usefMRI-based diagnostic scheme and the onecial effect of shunt surgery for patients witdiagnosis of iNPH is established in terms osurgery, and the efficacy of surgery dependtic accuracy. Therefore, there is an interacthe accuracy of the diagnostic scheme andof the treatment. Nevertheless, we achievedment rate of 69.0% on daily life activity, whthat all the procedures, including diagnosment, yield reasonable net benefits. Furtproved that the diagnostic scheme has apredictive value, as the percentage of subjefound at one evaluation point to have respVP shunt was 80.0% for the whole groupcates that MRI-based diagnosis is useful fosis of iNPH.Assessment of the outcome in iNPH pimportant issue; activity of daily life woTable 2 Combination of symptomsCombination of symptoms* No. of patientsTriad 51Gait and cognitive 23Gait and urinary 5Cognitive and urinary 3Gait only 12Cognitive only 3Urinary only 1Subjective symptoms only 2Table 1 Background characteristics for patients in studyAge (years) 74.5 ± 5.1Sex (male) 58%Education (years) 10.2 ± 2.9Systolic pressure (mmHg) 131.0 ± 14.6Diastolic pressure (mmHg) 75.7 ± 8.9History of hypertension 60%History of diabetes 20%History of a lipid disorder 31%Smoking statusCurrently 10%Previously 37%Medications (% present)L-dopa/dopamine agonist 10%Hashimoto et al. Cerebrospinal Fluid Research 2010, 7:18http://www.cerebrospinalfluidresearch.com/content/7/1/18Page 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)Cerebrospinal Fluid Research 2010, 7:18study, clinical improvement was defined as at least a onelevel improvement on mRS. The mRS is the most popu-lar assessment of global outcome in stroke [16], and hastreated 101 patients with iNPH with VP shunt by usingfixed pressure valves, and yielded a one-year improve-ment rate of 59% based on mRS [24]. The group reportedFigure 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, 7:18http://www.cerebrospinalfluidresearch.com/content/7/1/18Page 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 broadclassifications of disability, only sizable changes can bedetected [22]. Moreover, inter-rater reliability may be animportant source of error with the mRS. However, inthis study, improvements were detected in a large pro-portion of the subjects, suggesting a significant treat-ment effect. The improvements were also confirmed onall 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 thesubgroup with unfavorable outcome, where no improve-ment or deterioration was recorded on the less sensitivemRS. Therefore, if the low sensitivity of the mRS istaken into consideration, the outcome in this study isacceptable.Serious adverse events occurred in 15 patients, and allbut three of these were unrelated to the operation or VPshunt. Considering the subjects’ mean age of 75 years,vascular events, malignancies, infections, and fractureswere not uncommon. Outcomes for those who experi-enced an SAE were generally unfavorable, as would beexpected. In addition, asymptomatic subdural effusion (n= 13) and orthostatic headache (n = 8) were reported asnon-serious shunt-related adverse events. These werecontrolled well by adjustment of valve pressure [24].Although a considerable number of retrospective caseseries have been published [26-28], prospective studiesusing standardized validated outcome measures, whichare comparable to the present study, are very scarce. TheDutch NPH study group, in their prospective study,transient and persistent subdural effusion in 53% ofTable 3 Changes of outcome measures with eachoutcome group.Baseline 12 months p value*INPHGS gait scoreAll patients 2 (2.3-2.6) 1 (1.2-1.7) < 0.001Favorable outcome 2 (2.3-2.6) 1 (0.8-1.3) < 0.001Unfavorable outcome 2 (2.1-2.7) 2 (1.9-2.8) nsiNPHGS cognitive scoreAll patients 2 (2.1-2.4) 1 (1.3-1.7) < 0.001Favorable outcome 2 (2.0-2.5) 1 (1.0-1.5) < 0.001Unfavorable outcome 2 (1.8-2.6) 2 (1.6-2.4) nsiNPHGS urinary scoreAll patients 2 (1.7-2.2) 1 (0.8-1.3) < 0.001Favorable outcome 2 (1.5-2.1) 1 (0.5-0.9) < 0.001Unfavorable outcome 2 (1.8-2.8) 2 (1.4-2.4) nsiNPHGS total scoreAll patients 6 (6.1-7.1) 4 (3.4-4.6) < 0.001Favorable outcome 6 (5.9-7.1) 2 (2.4-3.6) < 0.001Unfavorable outcome 6 (5.9-7.9) 5 (5.1-7.5) nsTimed “up & go” test (seconds)All patients 20.5 (16-30) 14 (11-20) < 0.001Favorable outcome 20 (16.5-28) 13 (10-17) < 0.001Unfavorable outcome 22 (15-41) 20 (13-33) 0.004MMSEAll patients 23 (16.3-26) 25 (20.3-28) < 0.001Favorable outcome 23 (15.5-26) 25 (21.5-28) < 0.001Unfavorable outcome 23 (17-25) 24 (16-27) nsData 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.Cerebrospinal Fluid Research 2010, 7:18