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未破裂脳動脈瘤

著者: 吉田和道 京都大学大学院医学研究科脳神経外科学

著者: 宮本享 京都大学大学院医学研究科脳神経外科学

監修: 甲村英二 公立学校共済組合 近畿中央病院

著者校正/監修レビュー済:2021/03/10
参考ガイドライン:
  1. 日本脳卒中学会:脳卒中治療ガイドライン 2015(追補2019対応)
患者向け説明資料

概要・推奨   

  1. 未破裂脳動脈瘤の診断は、カテーテル法によるDSA: digital subtraction angiographyや3次元血管撮影、3D-CTA: 3次元ヘリカルコンピュータートモグラフィー、MRA: magnetic resonance angiography (1.5T以上)により診断されることが望ましい(推奨度1)
  1. 未破裂脳動脈瘤が発見された場合の初期対応
  1. 未破裂脳動脈瘤が診断された場合、年齢・健康状態などの患者の背景因子、サイズや部位・形状など病変の特徴、未破裂脳動脈瘤の自然歴(年間出血率)などの正確な情報を患者に示し、施設や術者の治療成績を勘案して、治療の適応を検討する。その際、今後の方針について文書によるインフォームドコンセントを行うことが推奨される(推奨度2)。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
吉田和道 : 特に申告事項無し[2021年]
宮本享 : 講演料(ファイザー株式会社,第一三共株式会社),奨学(奨励)寄付など(中外製薬株式会社,シーメンスヘルスケア株式会社,日本光電株式会社,株式会社フィリップス・ジャパン)[2021年]
監修:甲村英二 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行い、わが国の未破裂脳動脈瘤破裂リスクの評価法と、血管内治療の手術法に関する情報をアップデートした。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 未破裂脳動脈瘤とは、破裂した形跡のない脳動脈瘤である(<図表><図表><図表>)。発見の契機により、症候性と無症候性に分類される。
 
ブレブを有する未破裂中大脳動脈瘤

a:正面からみたMRA。右・中大脳動脈分岐部に6×11mm大の動脈瘤を認める。
b:右・内頚動脈造影(3-D DSA)。ドームの先端から内側に突出するブレブ(→)を認める。
c:右・前頭側頭開頭によるクリッピング術の術中写真。動脈瘤のブレブ(→)は、動脈瘤壁も薄く内部の血流が透見できる状態で、破裂リスクの高い動脈瘤であった可能性を示唆している。

出典

img1:  著者提供
 
 
 
右・内頚動脈‐後交通動脈分岐部にできた巨大動脈瘤

a:上方からみたCTA。左・内頚動脈‐後交通動脈分岐部にも4mm大の動脈瘤がある。
b:MRI T2強調像では、瘤内がflow voidとして描出され、瘤内血栓は伴わない。
c:右・内頚動脈造影(3D-DSA)では、動脈瘤頚部付近から分枝する後交通動脈(→)が明瞭に描出されている。

出典

img1:  著者提供
 
 
 
多発性脳動脈瘤

上方からみた頭部CTA。3個の未破裂脳動脈瘤が認められる。右・内頚動脈‐後交通動脈分岐部動脈瘤(1)、右・中大脳動脈分岐部動脈瘤(2, 3)

出典

img1:  著者提供
 
 
 
  1. 症候化の原因として最も重要な破裂のほかに、瘤による神経圧迫症状や瘤内血栓による脳塞栓症などがある。
  1. MR血管造影法(MRA)やCT血管造影法(CTA)の普及により、未破裂脳動脈瘤が発見される機会は増加している。
 
  1. 成人の未破裂脳動脈瘤の有病率は2~5程度と推測される。
  1. 対象とする母集団と調査方法により未破裂脳動脈瘤の有病率に関する報告にはかなりの違いがある。日本における久山町研究の前向きに観察した1,230例の剖検例による調査では、2.2%に未破裂脳動脈瘤が発見された[1]。年齢とともに有病率は上昇し、70歳以上の高齢者においては、7~14%程度との報告がある[2]
  1. 未破裂脳動脈瘤発生のハイリスク患者として、クモ膜下出血の既往、結合組織病の合併(多発性嚢胞腎、線維筋形成不全、Ehlers-Danlos IV型、Marfan症候群など)、家族歴などが報告されている。クモ膜下出血の精査中に多発性動脈瘤として未破裂脳動脈瘤が発見される頻度は、20~30%とされる[3]。多発性嚢胞腎患者の未破裂脳動脈瘤合併率は10%程度と報告されている[4]。家族性脳動脈瘤については、2親等以内にクモ膜下出血の家族歴をもつ健常者の13.9%に[5]、さらに、1親等以内の同胞では一般の4倍の頻度で未破裂脳動脈瘤が発見される[6]
 
  1. 未破裂脳動脈瘤の破裂率
  1. 一般的に日本における5mm以上の未破裂動脈瘤の年間破裂率は1%前後と考えられている[7][8][1]
  1. 大きさ・形状・部位などにより破裂の危険性は異なる。
  1. 破裂リスクの高い動脈瘤:大きい動脈瘤、症候性の脳動脈瘤、不規則な瘤の形状・ブレブの存在、Dome-Neck Aspect比の高いもの、前交通動脈瘤、内頚動脈‐後交通動脈一部、大きな脳底動脈瘤、高齢者、女性、多発性、クモ膜下出血の既往、喫煙 など[9][10][11][12][13][14][15][16][17][18]
  1. 現在までに未破裂脳動脈瘤の破裂率に関するレベルの高い十分なエビデンスは蓄積されていない。
  1. 欧米の53施設で行われた国際未破裂脳動脈瘤研究(ISUIA)では1998年にその中間報告がなされ、さらに2003年に前向き(prospective)データの報告が追加されている[12]。破裂率について、前向き経過観察(1,692症例、2,686瘤・平均4.1年、6,544人・年)では、クモ膜下出血の既往のない群(Group1)における瘤7mm以下の未破裂脳動脈瘤のうち、A群(内頚動脈、前交通動脈、中大脳動脈瘤)では5年間に0%、P群(椎骨脳底動脈瘤と内頚動脈-後交通動脈瘤)では2.5%(年間0.5%)、破裂脳動脈瘤に合併した群(Group2)において、では、A群1.5%(年間0.3%)、P群3.4%(年間0.7%)であった。サイズがより大きな脳動脈瘤ではグループ間での差は明らかではなく、7~12mmではA群2.6%(年間0.5%)、P群14.5%(年間2.9%)、13~24mmではA群14.5%(年間2.9%)、P群18.4%(年間3.7%)、25mm以上ではA群40%(年間8%)、P群50%(年間10%)であった。5年間死亡率は12.7%で破裂を認めた51例中33例(65%)が死亡した。
  1. 未破裂脳動脈瘤の頻度に関して人種別の差はいまだ明らかではない。しかしクモ膜下出血発症率はフィンランドと日本において他の地域よりも高いとされているため、未破裂脳動脈瘤の破裂率が人種別で異なる可能性もある。Wermerらのメタ解析(19論文より4,795患者、2万6,122人・年)では、未破裂脳動脈瘤の年間破裂率は5年以下の観察で1.2%、5~10年で0.6%、10年以上で1.3%と経過観察年数で破裂率がやや異なり、サイズによっても異なり5mm以下でも0.5%、5~10mmで1.2%、10mm以上で1.5%であった。有意差をもつ因子は、5mm以上の大きさ、後方循環、症候性、また日本およびフィンランドの研究であった[16][19]
  1. 日本の大規模前向き研究(UCAS Japan)によれば、3mm以上の動脈瘤全体の平均年間破裂率は、0.95%であった。大きさとともに破裂率は上昇し、5mm未満の動脈瘤(年間破裂率:0.36%)よりも7~9mmの動脈瘤の破裂率は3.35倍に上昇する。部位別では前交通動脈瘤と後交通動脈瘤の破裂率が高く、形状に関してはブレブを有する瘤の破裂率が高かった[20]
  1. UCAS Japanのデータを基に、日本人の未破裂脳動脈瘤の破裂リスクを予測するための、UCASスコアが提唱されている[21]。破裂危険因子として、年齢・性別・高血圧の有無・大きさ・部位・ブレブの有無を基に点数化し(0~15点)、3年内の破裂リスクを4段階に分類している。UCASスコアの自動計算式は未破裂脳動脈瘤情報サイトU-infoに登録されている。米倉らは5mm未満の小型未破裂脳動脈瘤を全例(329例・380病変)、前向きに観察するSUAVe研究を行っており、375人・年の経過観察で3人に破裂(0.8%/年 95%CI:0.2-3%)、18病変(4.7%)に2mm以上の拡大が認められたと報告している。拡大や破裂に関与する因子として多発性・女性・70歳以上の高齢、部位として前交通動脈瘤および脳底動脈瘤を挙げている[22]
  1. その他、未破裂脳動脈瘤に関するわが国の研究結果として、年間破裂率については1.9~2.7%となっており、サイズが大きいもの、後方循環、症候性、多発性および多房性の形状などが破裂のリスクが高い因子であるという報告がある一方で、合併疾患や瘤の部位による破裂率の差は認めないとする報告もある[13][14][15]
問診・診察のポイント  
  1. 症候性未破裂脳動脈瘤では、内頚動脈後交通動脈分岐部動脈瘤における動眼神経麻痺(一側眼瞼下垂)など、圧迫症状が瘤の急速な増大すなわち切迫破裂を意味する場合がある。

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文献 

著者: H Iwamoto, Y Kiyohara, M Fujishima, I Kato, K Nakayama, K Sueishi, M Tsuneyoshi
雑誌名: Stroke. 1999 Jul;30(7):1390-5.
Abstract/Text BACKGROUND AND PURPOSE: Subarachnoid hemorrhage is a life-threatening disease that occurs mostly because of the rupture of intracranial saccular aneurysms. However, little is known about the prevalence of ruptured and unruptured aneurysms in the general population. The aim of the present study was to examine the prevalence of intracranial aneurysms on the basis of a consecutive autopsy series over a 30-year observation period in a general Japanese population in Hisayama.
METHODS: We evaluated 1230 consecutive autopsy cases with craniotomy among the total deaths of Hisayama residents during 1962 through 1991 (overall autopsy rate, 80.1%).
RESULTS: A total of 73 intracranial saccular aneurysms were found in 57 cases (4.6%). The prevalence of aneurysms for women was 2.4 times higher than that for men (7.1% versus 2.9%). Among men, the prevalence of aneurysms remained unchanged across the range of age groups. In contrast, there were 2 peaks in the prevalence of aneurysms for women falling in the 40- to 49-year (14.3%) and 60- to 69-year age groups (14.5%). The most common site of the aneurysms was the middle cerebral artery (31.5%), followed by the anterior communicating artery (30.1%), anterior cerebral artery (15.1%), vertebrobasilar artery (12.3%), and internal carotid artery (11.0%). Among these 73 aneurysms, 29 (39.7%) were ruptured. Ruptured aneurysms were common in subjects <80 years of age, whereas unruptured aneurysms were prevalent in those >/=80 years of age. The frequency of ruptured aneurysms was highest in the vertebrobasilar system (66.7%) and lowest in the middle cerebral artery (13.0%).
CONCLUSIONS: Our data suggest that intracranial aneurysms are more frequent in women in the general Japanese population. Aneurysms are more prevalent in the middle cerebral artery, but the risk of rupture is highest in the vertebrobasilar system.

PMID 10390312  Stroke. 1999 Jul;30(7):1390-5.
著者: M Nemoto, N Yasui, A Suzuki, I Sayama
雑誌名: Neurol Med Chir (Tokyo). 1991 Dec;31(13):892-8.
Abstract/Text A series of 105 patients presenting with multiple aneurysms and subarachnoid hemorrhage (SAH) were operated on for ruptured and unruptured aneurysms between 1976 and 1984. Clinical factors other than the severity of SAH affecting the outcomes included: 1) Misdiagnosis of the location of a ruptured aneurysm among multiple aneurysms resulted in poor outcomes because of multiple surgical approaches or rebleeding during the acute period. 2) Combinations of aneurysmal locations requiring multiple surgical approaches, such as interhemispheric and transsylvian, during the acute stage caused worse outcomes than with multi-stage surgeries. If an unruptured aneurysm could not be reached during the initial exposure, multi-stage surgery was safe if the ruptured aneurysm had been clipped during the acute period. 3) Complications occurring during unruptured aneurysm surgery. The patient's age, the location and size of the unruptured aneurysms were significant factors in the clinical prognosis. Surgery for unruptured aneurysm caused 1.8% morbidity in patients between 28 and 55 years, but 18.0% morbidity in patients over 56 years of age. Surgery for internal carotid artery aneurysms resulted in 14.8% overall morbidity. Surgery for middle cerebral and anterior cerebral artery aneurysms caused below 5% morbidity. Postoperative morbidity in patients with aneurysms less than 5 mm in diameter was 1.3%, and with aneurysms measuring 10 mm or more, 20%. The optimum treatment for multiple aneurysms with SAH should be based on all factors of the patient's condition, including the unruptured aneurysms.

PMID 1726249  Neurol Med Chir (Tokyo). 1991 Dec;31(13):892-8.
著者: J Huston, V E Torres, P P Sulivan, K P Offord, D O Wiebers
雑誌名: J Am Soc Nephrol. 1993 Jun;3(12):1871-7.
Abstract/Text The association of intracranial aneurysms with autosomal dominant polycystic kidney disease (ADPKD), the 30-day mortality rate exceeding 50% for aneurysmal rupture, the effectiveness of surgical repair of unruptured aneurysms with a low surgical risk, and the development of noninvasive imaging techniques for their detection have led physicians to consider the value of screening patients with ADPKD for unruptured intracranial aneurysms. The sensitivity and specificity of high-resolution computed tomography and magnetic resonance imaging for the diagnosis of small intracranial aneurysms have been disappointing. To determine the value of magnetic resonance angiography (MRA), 85 patients with ADPKD without symptoms related to an intracranial aneurysm and 2 patients with ADPKD presenting with a subarachnoid hemorrhage or a suspected aneurysmal leak were studied. MRA was performed with the Multisequence Vascular Package (GE Medical Systems) with use of three-dimensional time-of-flight and three-dimensional phase-contrast techniques, and postprocessing maximum intensity projection images were generated to eliminate the problem of overlapping vessels. Asymptomatic intracranial aneurysms were detected in 6 (22%) of 27 patients with and 3 (5%) of 56 patients without a family history of intracranial aneurysm or subarachnoid hemorrhage (P = 0.02, information missing in 2 patients) and in the 2 patients who presented with a symptomatic aneurysm. A stepwise logistic regression analysis indicated that a family history of intracranial aneurysm or subarachnoid hemorrhage was independently associated with the presence of intracranial aneurysms. All of the aneurysms were < or = 6.5 mm in diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 8338918  J Am Soc Nephrol. 1993 Jun;3(12):1871-7.
著者: T Nakagawa, K Hashi, Y Kurokawa, A Yamamura
雑誌名: J Neurosurg. 1999 Sep;91(3):391-5. doi: 10.3171/jns.1999.91.3.0391.
Abstract/Text OBJECT: Previously the authors reported a significant correlation between a family history of subarachnoid hemorrhage (SAH) and the discovery of an unruptured aneurysm in a group of healthy volunteers. This study corroborates and extends previous findings regarding the relationship between genetic and acquired factors in the formation of cerebral aneurysms.
METHODS: The incidence of asymptomatic, unruptured cerebral aneurysms was studied among patients with a family history of SAH within the second degree of consanguinity. Forty-one unruptured cerebral aneurysms were found in 34 (13.9%) of 244 patients. This incidence was significantly higher than that found in a control group of healthy volunteers (6%). Furthermore, patients who had a family history of SAH combined with multiple systemic risk factors were found to have the highest incidence of unruptured aneurysms (32%; odds ratio 3.49, 95% confidence interval 1.37-8.9).
CONCLUSIONS: These findings suggest that patients with a family history of SAH with or without the presence of more than one systemic risk factor are at significantly higher risk of harboring cerebral aneurysms. This high-risk group should be periodically screened and treated with appropriate surgical or other forms of therapy when necessary.

PMID 10470812  J Neurosurg. 1999 Sep;91(3):391-5. doi: 10.3171/jns.199・・・
著者: A Ronkainen, J Hernesniemi, M Puranen, L Niemitukia, R Vanninen, M Ryynänen, H Kuivaniemi, G Tromp
雑誌名: Lancet. 1997 Feb 8;349(9049):380-4. doi: 10.1016/S0140-6736(97)80009-8.
Abstract/Text BACKGROUND: We set out to determine the prevalence of incidental intracranial aneurysms in first-degree relatives aged 30 years or more of people with intracranial aneurysms, and to see if polycystic kidney disease contributes to the aggregation of familial intracranial aneurysms.
METHODS: 91 families with two or more affected members had previously been identified from a 14 year series of 1150 intracranial aneurysm patients treated at the University Hospital of Kuopio, Finland. Magnetic resonance angiography was used as a preliminary screening method, followed by conventional four-vessel angiography to verify suspected aneurysms. Participants were also screened for polycystic kidneys by ultrasonography.
FINDINGS: Incidental aneurysms were detected in 40 individuals: 38 of 438 individuals from 85 families without polycystic kidney disease or other diagnosed heritable disorders, and two of 22 individuals from six families known to have polycystic kidney disease. The crude and age-adjusted prevalence of incidental intracranial aneurysms among screened first-degree relatives was 8.7 (SE 1.3)% (95% CI 6.2-11.7) and 9.1 (1.4)% (6.2-11.7), respectively, for the familial group and the crude prevalence for the polycystic kidney group was 9.1 (6.1)% (1.1-29.2).
INTERPRETATION: Our results demonstrate a high prevalence of incidental intracranial aneurysms among first-degree relatives aged 30 years or older of patients with the condition and indicate that the risk of having an aneurysm is about four times higher for a close relative than for someone from the general population. Also, polycystic kidney disease families are a small fraction of the familial intracranial aneurysm families.

PMID 9033463  Lancet. 1997 Feb 8;349(9049):380-4. doi: 10.1016/S0140-・・・
著者: W F McCormick, G J Acosta-Rua
雑誌名: J Neurosurg. 1970 Oct;33(4):422-7. doi: 10.3171/jns.1970.33.4.0422.
Abstract/Text
PMID 5471931  J Neurosurg. 1970 Oct;33(4):422-7. doi: 10.3171/jns.197・・・
著者: W I Schievink, J E Parisi, D G Piepgras
雑誌名: Neurosurgery. 1997 Dec;41(6):1247-51; discussion 1251-2.
Abstract/Text OBJECTIVE: Familial intracranial aneurysms are more common than has been appreciated, but systematic autopsy studies of affected individuals have not been reported. We reviewed the autopsy findings of a group of patients with familial aneurysms to elucidate the nature of the putative underlying arteriopathy.
METHODS: Using a computerized diagnostic index, we identified all patients with intracranial aneurysms in whom postmortem examination had been performed at the Mayo Clinic between January 1, 1992, and December 31, 1994. The medical records, radiographic studies, and autopsy findings of these patients were reviewed.
RESULTS: Among the 28 patients with intracranial aneurysms, 3 (11%) had one or more first-degree relatives with documented intracranial aneurysms. The mean age of the three patients (two women and one man) was 54 years. Microscopic examination of the vascular system revealed medial changes, consisting of degeneration of elastic fibers and increased ground substance, in the systemic arteries of 2 of the 3 patients with familial aneurysms but in none of the 25 patients with sporadic aneurysms. These nonspecific medial changes involved both common and extracranial internal carotid arteries in one patient and the entire aorta as well as intracranial and common carotid arteries in the other patient.
CONCLUSION: These observations suggest that an underlying arteriopathy in patients with familial intracranial aneurysms involves the tunica media and commonly may affect systemic (extracranial) arteries.

PMID 9402575  Neurosurgery. 1997 Dec;41(6):1247-51; discussion 1251-2・・・
著者: G J Rinkel, M Djibuti, A Algra, J van Gijn
雑誌名: Stroke. 1998 Jan;29(1):251-6.
Abstract/Text BACKGROUND AND PURPOSE: The estimates on the prevalence and the risk of rupture of intracranial saccular aneurysms vary widely between studies. We conducted a systematic review on prevalence and risk of rupture of intracranial aneurysms and classified the data according to study design, study population, and aneurysm characteristics.
METHODS: We searched for studies published between 1955 and 1996 by means of a MEDLINE search and a cumulative review of the reference lists of all relevant publications. Two authors independently assessed eligibility of all studies and extracted data on study design and on numbers and characteristics of patients and aneurysms.
RESULTS: For data on prevalence we found 23 studies, totalling 56,304 patients; 6685 (12%) of these patients were from 15 angiography studies. Prevalence was 0.4% (95% confidence interval, 0.4% to 0.5%) in retrospective autopsy studies, 3.6% (3.1 to 4.1) for prospective autopsy studies, 3.7% (3.0 to 4.4) in retrospective angiography studies, and 6.0% (5.3 to 6.8) in prospective angiography studies. For adults without specific risk factors, the prevalence was 2.3% (1.7 to 3.1); it tended to increase with age. The prevalence was higher in patients with autosomal dominant polycystic kidney disease (relative risk [RR], 4.4 [2.7 to 7.2]), a familial predisposition (RR, 4.0 [2.7 to 6.0]), or atherosclerosis (RR, 2.3 [1.7 to 3.1]). Only 8% (5 to 11) of the aneurysms were >10 mm. For the risk of rupture, we found nine studies, totalling 3907 patient-years. The overall risk per year was 1.9% (1.5 to 2.4); for aneurysms = 10 mm, the annual risk was 0.7% (0.5 to 1.0). The risk was higher in women (RR, 2.1[1.1 to 3.9]) and for aneurysms that were symptomatic (RR, 8.3 [4.0 to 17]), >10 mm (RR, 5.5 [3.3 to 9.4]), or in the posterior circulation (RR, 4.1 [1.5 to 11]).
CONCLUSIONS: Data on prevalence and risk of rupture vary considerably according to study design, study population, and aneurysm characteristics. If all available evidence with inherent overestimation and underestimation is taken together, for adults without risk factors for subarachnoid hemorrhage, aneurysms are found in approximately 2%. The vast majority of these aneurysms are small (=10 mm) and have an annual risk of rupture of approximately 0.7%.

PMID 9445359  Stroke. 1998 Jan;29(1):251-6.
著者: S Juvela, M Porras, K Poussa
雑誌名: J Neurosurg. 2000 Sep;93(3):379-87. doi: 10.3171/jns.2000.93.3.0379.
Abstract/Text OBJECT: The authors conducted a study to investigate the long-term natural history of unruptured intracranial aneurysms and the predictive risk factors determining subsequent rupture in a patient population in which surgical selection of cases was not performed.
METHODS: One hundred forty-two patients with 181 unruptured aneurysms were followed from the 1950s until death or the occurrence of subarachnoid hemorrhage or until the years 1997 to 1998. The annual and cumulative incidence of aneurysm rupture as well as several potential risk factors predictive of rupture were studied using lifetable analyses and Cox's proportional hazards regression models including time-dependent covariates. The median follow-up time was 19.7 years (range 0.8-38.9 years). During 2575 person-years of follow up, there were 33 first-time episodes of hemorrhage from previously unruptured aneurysms, for an average annual incidence of 1.3%. In 17 patients, hemorrhage led to death. The cumulative rate of bleeding was 10.5% at 10 years, 23% at 20 years, and 30.3% at 30 years after diagnosis. The diameter of the unruptured aneurysm (relative risk [RR] 1.11 per mm in diameter, 95% confidence interval [CI] 1-1.23, p = 0.05) and patient age at diagnosis inversely (RR 0.97 per year, 95% CI 0.93-1, p = 0.05) were significant independent predictors for a subsequent aneurysm rupture after adjustment for sex, hypertension, and aneurysm group. Active smoking status at the time of diagnosis was a significant risk factor for aneurysm rupture (RR 1.46, 95% CI 1.04-2.06, p = 0.033) after adjustment for size of the aneurysm, patient age, sex, presence of hypertension, and aneurysm group. Active smoking status as a time-dependent covariate was an even more significant risk factor for aneurysm rupture (adjusted RR 3.04, 95% CI 1.21-7.66, p = 0.02).
CONCLUSIONS: Cigarette smoking, size of the unruptured intracranial aneurysm, and age, inversely, are important factors determining risk for subsequent aneurysm rupture. The authors conclude that such unruptured aneurysms should be surgically treated regardless of their size and of a patient's smoking status, especially in young and middle-aged adults, if this is technically possible and if the patient's concurrent diseases are not contraindications. Cessation of smoking may also be a good alternative to surgery in older patients with small-sized aneurysms.

PMID 10969934  J Neurosurg. 2000 Sep;93(3):379-87. doi: 10.3171/jns.20・・・
著者:
雑誌名: N Engl J Med. 1998 Dec 10;339(24):1725-33. doi: 10.1056/NEJM199812103392401.
Abstract/Text BACKGROUND: The management of unruptured intracranial aneurysms requires knowledge of the natural history of these lesions and the risks of repairing them.
METHODS: A total of 2621 patients at 53 participating centers in the United States, Canada, and Europe were enrolled in the study, which had retrospective and prospective components. In the retrospective component, we assessed the natural history of unruptured intracranial aneurysms in 1449 patients with 1937 unruptured intracranial aneurysms; 727 of the patients had no history of subarachnoid hemorrhage from a different aneurysm (group 1), and 722 had a history of subarachnoid hemorrhage from a different aneurysm that had been repaired successfully (group 2). In the prospective component, we assessed treatment-related morbidity and mortality in 1172 patients with newly diagnosed unruptured intracranial aneurysms.
RESULTS: In group 1, the cumulative rate of rupture of aneurysms that were less than 10 mm in diameter at diagnosis was less than 0.05 percent per year, and in group 2, the rate was approximately 11 times as high (0.5 percent per year). The rupture rate of aneurysms that were 10 mm or more in diameter was less than 1 percent per year in both groups, but in group 1, the rate was 6 percent the first year for giant aneurysms (> or =25 mm in diameter). The size and location of the aneurysm were independent predictors of rupture. The overall rate of surgery-related morbidity and mortality was 17.5 percent in group 1 and 13.6 percent in group 2 at 30 days and was 15.7 percent and 13.1 percent, respectively, at 1 year. Age independently predicted surgical outcome.
CONCLUSIONS: The likelihood of rupture of unruptured intracranial aneurysms that were less than 10 mm in diameter was exceedingly low among patients in group 1 and was substantially higher among those in group 2. The risk of morbidity and mortality related to surgery greatly exceeded the 7.5-year risk of rupture among patients in group 1 with unruptured intracranial aneurysms smaller than 10 mm in diameter.

PMID 9867550  N Engl J Med. 1998 Dec 10;339(24):1725-33. doi: 10.1056・・・
著者: David O Wiebers, J P Whisnant, J Huston, I Meissner, R D Brown, D G Piepgras, G S Forbes, K Thielen, D Nichols, W M O'Fallon, J Peacock, L Jaeger, N F Kassell, G L Kongable-Beckman, J C Torner, International Study of Unruptured Intracranial Aneurysms Investigators
雑誌名: Lancet. 2003 Jul 12;362(9378):103-10.
Abstract/Text BACKGROUND: The management of unruptured intracranial aneurysms is controversial. Investigators from the International Study of Unruptured Intracranial Aneurysms aimed to assess the natural history of unruptured intracranial aneurysms and to measure the risk associated with their repair.
METHODS: Centres in the USA, Canada, and Europe enrolled patients for prospective assessment of unruptured aneurysms. Investigators recorded the natural history in patients who did not have surgery, and assessed morbidity and mortality associated with repair of unruptured aneurysms by either open surgery or endovascular procedures.
FINDINGS: 4060 patients were assessed-1692 did not have aneurysmal repair, 1917 had open surgery, and 451 had endovascular procedures. 5-year cumulative rupture rates for patients who did not have a history of subarachnoid haemorrhage with aneurysms located in internal carotid artery, anterior communicating or anterior cerebral artery, or middle cerebral artery were 0%, 2. 6%, 14 5%, and 40% for aneurysms less than 7 mm, 7-12 mm, 13-24 mm, and 25 mm or greater, respectively, compared with rates of 2 5%, 14 5%, 18 4%, and 50%, respectively, for the same size categories involving posterior circulation and posterior communicating artery aneurysms. These rates were often equalled or exceeded by the risks associated with surgical or endovascular repair of comparable lesions. Patients' age was a strong predictor of surgical outcome, and the size and location of an aneurysm predict both surgical and endovascular outcomes.
INTERPRETATION: Many factors are involved in management of patients with unruptured intracranial aneurysms. Site, size, and group specific risks of the natural history should be compared with site, size, and age-specific risks of repair for each patient.

PMID 12867109  Lancet. 2003 Jul 12;362(9378):103-10.
著者: S Asari, T Ohmoto
雑誌名: Clin Neurol Neurosurg. 1993 Sep;95(3):205-14.
Abstract/Text We report the results of a statistical analysis of the long-term outcome of 54 patients with 72 unruptured cerebral aneurysms, and identify the factors for predicting subsequent ruptures. Twenty-two patients died during the observation period, which averaged 43.7 months. The 5-year survival rate was 56%. Aneurysms ruptured in 11 patients (20.4%), 10 of whom died without undergoing surgery. The annual bleeding rate was 1.92%. The average size of the 11 ruptured aneurysms was 13.1 mm. In 4 patients, however, bleeding occurred in unruptured cerebral aneurysms of 4 and 5 mm, which suggests that leaving unruptured cerebral aneurysms of less than 10 mm in size untreated is hazardous. According to the Cox proportional hazards model, the shape and location of the aneurysm and the presence of hypertension were the most important factors for predicting a subsequent rupture. Our data suggest that unruptured cerebral aneurysms arising from the vertebrobasilar and middle cerebral arteries of 10-19 mm size and of multilobes had a statistically high probability of subsequent bleeding. Although 20 patients with 28 unruptured cerebral aneurysms were followed through repeated examinations, we could not correlate the risk of subsequent bleeding with changes in the size of the aneurysm.

PMID 8242963  Clin Neurol Neurosurg. 1993 Sep;95(3):205-14.
著者: N Yasui, A Suzuki, H Nishimura, K Suzuki, T Abe
雑誌名: Neurosurgery. 1997 Jun;40(6):1155-9; discussion 1159-60.
Abstract/Text OBJECTIVE: The purpose of this study was to clarify the risk of rupture of unruptured intracranial aneurysms among large groups of patients with various underlying diseases or conditions.
METHODS: A long-term follow-up study of unruptured intracranial aneurysms was performed with 360 patients who were treated conservatively during the period from April 1969 to December 1992.
RESULTS: Follow-up evaluation (between February and June 1994) could be performed for 234 (65%) of the patients. The underlying diseases included multiple aneurysms with subarachnoid hemorrhage for 60 patients, cerebral infarction for 108, intracerebral hemorrhage for 27, and other diseases for 39. Single aneurysms were present in 171 patients and multiple aneurysms in 63. The mean follow-up period was 75 months (range, 3-270 mo). Of the 234 patients, 132 (56.4%) survived, 59 (25.2%) died because of other diseases, 9 (3.8%) underwent surgery, and 34 (14.5%) showed bleeding from unruptured aneurysms, which was fatal for 18 of the patients. The average annual rupture rate for all patients was 2.3% (subarachnoid hemorrhage, 3.2%; cerebral infarction, 2.2%; intracerebral hemorrhage, 3.2%; other diseases, 3.6%). There were no significant differences among the patients according to underlying disease or aneurysm site. The cumulative rate of bleeding for all patients was 20% at 10 years after diagnosis and 35% at 15 years. The cumulative probability of rupture was significantly higher for the multiple aneurysms than the single aneurysms (P < 0.001).
CONCLUSION: The risk of rupture of unruptured aneurysms is high, especially for multiple aneurysms, but there are no significant differences in the risk of rupture according to the underlying disease or the aneurysm location. Radical treatment should be considered for patients with unruptured intracranial aneurysms.

PMID 9179887  Neurosurgery. 1997 Jun;40(6):1155-9; discussion 1159-60・・・
著者: Akio Morita, Satoru Fujiwara, Kazuo Hashi, Hiroshi Ohtsu, Takaaki Kirino
雑誌名: J Neurosurg. 2005 Apr;102(4):601-6. doi: 10.3171/jns.2005.102.4.0601.
Abstract/Text OBJECT: Knowing the rate of rupture associated with unruptured cerebral aneurysms (UCAs) can help surgeons determine a case management strategy in patients harboring these lesions. According to large-scale cohort studies involving populations in North America and Europe, small unruptured aneurysms carry a very low risk of rupture. In Japan, however, there have been sporadic reports of higher rates of rupture. To identify the rupture risk associated with UCAs in the Japanese population, the authors systematically reviewed retrospective studies of the natural course of these lesions.
METHODS: The authors searched Medline and the Japan Medical Abstract Society Index for reports of UCAs in Japan. Two of the authors verified the eligibility of the reports and extracted data independently. Additional information was directly obtained from the authors of the original reports. Thirteen reports covering a total of 3801 patient-years fulfilled the criteria for our study. Subsequent rupture was documented in 104 patients and the annual rupture rate was 2.7% (95% confidence interval 2.2-3.3%). Large, posterior-circulation, and symptomatic aneurysms were associated with significantly higher rates of rupture (relative risks 6.4, 2.3, and 2.1, respectively). The risk of rupture determined by the authors' review was significantly higher than that reported by investigators from international cohort studies.
CONCLUSIONS: Although a selection bias of patients may be the cause of the higher rupture risk, untreated UCAs that have been followed in Japanese institutions have a considerably high rate of rupture. The natural course of UCAs should be carefully estimated in countries not included in the international studies.

PMID 15871500  J Neurosurg. 2005 Apr;102(4):601-6. doi: 10.3171/jns.20・・・
著者: Marieke J H Wermer, Irene C van der Schaaf, Ale Algra, Gabriël J E Rinkel
雑誌名: Stroke. 2007 Apr;38(4):1404-10. doi: 10.1161/01.STR.0000260955.51401.cd. Epub 2007 Mar 1.
Abstract/Text BACKGROUND AND PURPOSE: We updated our previous review from 1996 on the risk of rupture of unruptured intracranial aneurysms, aiming to include the newly published articles.
METHODS: We reviewed all studies from our former meta-analysis and performed a Medline search for new studies published after 1996. We calculated overall risks of rupture for studies with a mean follow-up time of <5, 5 to 10, and >10 years. Relative risks (RR) were calculated by comparing the risk of rupture in patients with and without potential risk factors. We aimed to perform multivariable analyses of the different risk factors with meta-regression analysis.
RESULTS: We included 19 studies (10 new) with 4705 patients and 6556 unruptured aneurysms (follow-up 26 122 patient-years). The overall rupture risks were 1.2% (follow-up <5 years), 0.6% (follow-up 5 to 10 years), and 1.3% (follow-up >10 years). In the univariable analysis, statistically significant risk factors for rupture were age >60 years (RR 2.0; 95% confidence interval [CI], 1.1 to 3.7), female gender (RR 1.6; 95% CI, 1.1 to 2.4), Japanese or Finnish descent (RR 3.4; 95% CI, 2.6 to 4.4), size >5 mm (RR 2.3; 95% CI, 1.0 to 5.2), posterior circulation aneurysm (RR 2.5; 95% CI, 1.6 to 4.1), and symptomatic aneurysm (RR 4.4; 95% CI, 2.8 to 6.8). Meta-regression analysis yielded implausible results.
CONCLUSIONS: Age, gender, population, size, site, and type of aneurysm should be considered in the decision whether to treat an unruptured aneurysm. Pooled multivariable analyses of individual data are needed to identify independent risk factors and to provide more reliable risk estimates for individual patients.

PMID 17332442  Stroke. 2007 Apr;38(4):1404-10. doi: 10.1161/01.STR.000・・・
著者: H Ujiie, Y Tamano, K Sasaki, T Hori
雑誌名: Neurosurgery. 2001 Mar;48(3):495-502; discussion 502-3.
Abstract/Text OBJECTIVE: The present retrospective study was undertaken to prove the reliability of the aspect ratio (aneurysm depth to aneurysm neck width) for predicting an aneurysmal rupture. The aspect ratio is considered a better geometric index than aneurysm size for determining the intra-aneurysmal blood flow.
METHODS: We measured the aspect ratios and the sizes of aneurysms, as determined by examining angiographic films magnified 1.4x, in 129 patients with ruptured aneurysms and in 72 patients with 78 unruptured aneurysms. After categorizing the aneurysms into four groups on the basis of their locations (aneurysms of the anterior communicating artery, middle cerebral artery, internal carotid artery-posterior communicating artery [ICA-PComA], and other aneurysms), a statistical analysis of ruptured and unruptured aneurysms was performed.
RESULTS: The mean aneurysm size was found to be statistically significant in the aneurysms at the ICA-PComA and in locations excluding the anterior communicating artery, the middle cerebral artery, and the ICA-PComA. However, the mean aspect ratio was statistically significant at all four locations. In patients with ruptured aneurysms, no ruptured aneurysms with an aspect ratio of less than 1.0 were found. The distribution of the ruptured group versus the unruptured group with an aspect ratio of less than 1.6 at each location was 13 versus 79%, respectively, at the anterior communicating artery, 11 versus 58% at the middle cerebral artery, 11% versus 85% at the ICA-PComA, and 7 versus 81% at other locations.
CONCLUSION: The aspect ratio between ruptured aneurysms and unruptured aneurysms was found to be statistically significant, and almost 80% of the ruptured aneurysms showed an aspect ratio of more than 1.6, whereas almost 90% of the unruptured aneurysms showed an aspect ratio of less than 1.6. This study therefore suggests that the aspect ratio may be useful in predicting imminent aneurysmal ruptures.

PMID 11270538  Neurosurgery. 2001 Mar;48(3):495-502; discussion 502-3.・・・
著者: Madhavan L Raghavan, Baoshun Ma, Robert E Harbaugh
雑誌名: J Neurosurg. 2005 Feb;102(2):355-62. doi: 10.3171/jns.2005.102.2.0355.
Abstract/Text OBJECT: The authors investigated whether quantified shape or size indices could better discriminate between ruptured and unruptured aneurysms.
METHODS: Several custom algorithms were created to quantifiy the size and shape indices of intracranial aneurysms by using three-dimensional computerized tomography angiography models of the brain vasculature. Data from 27 patients with ruptured or unruptured aneurysms were evaluated in a blinded fashion to determine whether aneurysm size or shape better discriminated between the ruptured and unruptured groups. Five size and eight shape indices were calculated for each aneurysm. Two-tailed independent Student t-tests (significance p < 0.05) were used to determine statistically significant differences between ruptured and unruptured aneurysm groups for all 13 indices. Receiver-operating characteristic-area under curve analyses were performed for all indices to quantify the predictability of each index and to identify optimal threshold values. None of the five size indices were significantly different between the ruptured and unruptured aneurysms. Five of the eight shape indices were significantly different between the two lesion groups, and two other shape indices showed a trend toward discriminating between ruptured and unruptured aneurysms, although these differences did not reach statistical significance.
CONCLUSIONS: Quantified shape is more effective than size in discriminating between ruptured and unruptured aneurysms. Further investigation will determine whether quantified aneurysm shape will prove to be a reliable predictor of aneurysm rupture.

PMID 15739566  J Neurosurg. 2005 Feb;102(2):355-62. doi: 10.3171/jns.2・・・
著者: T Ingall, K Asplund, M Mähönen, R Bonita
雑誌名: Stroke. 2000 May;31(5):1054-61.
Abstract/Text BACKGROUND AND PURPOSE: By official, mostly unvalidated statistics, mortality from subarachnoid hemorrhage (SAH) show large variations between countries. Using uniform criteria for case ascertainment and diagnosis, a multinational comparison of attack rates and case fatality rates of SAH has been performed within the framework of the WHO MONICA Project.
METHODS: In 25- to 64-year-old men and women, a total of 3368 SAH events were recorded during 35.9 million person-years of observation in 11 populations in Europe and China. Strict MONICA criteria were used for case ascertainment and diagnosis of stroke subtype. Case fatality was based on follow-up at 28 days after onset.
RESULTS: Age-adjusted average annual SAH attack rates varied 10-fold among the 11 populations studied, from 2.0 (95% CI 1.6 to 2.4) per 100 000 population per year in China-Beijing to 22.5 (95% CI 20.9 to 24.1) per 100 000 population per year in Finland. No consistent pattern was observed in the sex ratio of attack rates in the different populations. The overall 28-day case fatality rate was 42%, with 2-fold differences in age-adjusted rates between populations but little difference between men and women. Case fatality rates were consistently higher in Eastern than in Western Europe.
CONCLUSIONS: Using a uniform methodology, the WHO MONICA Project has shown very large variations in attack rates of SAH across 11 populations in Europe and China. The generally accepted view that women have a higher risk of SAH than men does not apply to all populations. Marked differences in outcome of SAH add to the wide gap in the burden of stroke between East and West Europe.

PMID 10797165  Stroke. 2000 May;31(5):1054-61.
著者: UCAS Japan Investigators, Akio Morita, Takaaki Kirino, Kazuo Hashi, Noriaki Aoki, Shunichi Fukuhara, Nobuo Hashimoto, Takeo Nakayama, Michi Sakai, Akira Teramoto, Shinjiro Tominari, Takashi Yoshimoto
雑誌名: N Engl J Med. 2012 Jun 28;366(26):2474-82. doi: 10.1056/NEJMoa1113260.
Abstract/Text BACKGROUND: The natural history of unruptured cerebral aneurysms has not been clearly defined.
METHODS: From January 2001 through April 2004, we enrolled patients with newly identified, unruptured cerebral aneurysms in Japan. Information on the rupture of aneurysms, deaths, and the results of periodic follow-up examinations were recorded. We included 5720 patients 20 years of age or older (mean age, 62.5 years; 68% women) who had saccular aneurysms that were 3 mm or more in the largest dimension and who initially presented with no more than a slight disability.
RESULTS: Of the 6697 aneurysms studied, 91% were discovered incidentally. Most aneurysms were in the middle cerebral arteries (36%) and the internal carotid arteries (34%). The mean (±SD) size of the aneurysms was 5.7±3.6 mm. During a follow-up period that included 11,660 aneurysm-years, ruptures were documented in 111 patients, with an annual rate of rupture of 0.95% (95% confidence interval [CI], 0.79 to 1.15). The risk of rupture increased with increasing size of the aneurysm. With aneurysms that were 3 to 4 mm in size as the reference, the hazard ratios for size categories were as follows: 5 to 6 mm, 1.13 (95% CI, 0.58 to 2.22); 7 to 9 mm, 3.35 (95% CI, 1.87 to 6.00); 10 to 24 mm, 9.09 (95% CI, 5.25 to 15.74); and 25 mm or larger, 76.26 (95% CI, 32.76 to 177.54). As compared with aneurysms in the middle cerebral arteries, those in the posterior and anterior communicating arteries were more likely to rupture (hazard ratio, 1.90 [95% CI, 1.12 to 3.21] and 2.02 [95% CI, 1.13 to 3.58], respectively). Aneurysms with a daughter sac (an irregular protrusion of the wall of the aneurysm) were also more likely to rupture (hazard ratio, 1.63; 95% CI, 1.08 to 2.48).
CONCLUSIONS: This study showed that the natural course of unruptured cerebral aneurysms varies according to the size, location, and shape of the aneurysm. (Funded by the Ministry of Health, Labor, and Welfare in Japan and others; UCAS Japan UMIN-CTR number, C000000418.).

PMID 22738097  N Engl J Med. 2012 Jun 28;366(26):2474-82. doi: 10.1056・・・
著者: Shinjiro Tominari, Akio Morita, Toshihiro Ishibashi, Tomosato Yamazaki, Hiroyuki Takao, Yuichi Murayama, Makoto Sonobe, Masahiro Yonekura, Nobuhito Saito, Yoshiaki Shiokawa, Isao Date, Teiji Tominaga, Kazuhiko Nozaki, Kiyohiro Houkin, Susumu Miyamoto, Takaaki Kirino, Kazuo Hashi, Takeo Nakayama, Unruptured Cerebral Aneurysm Study Japan Investigators
雑誌名: Ann Neurol. 2015 Jun;77(6):1050-9. doi: 10.1002/ana.24400. Epub 2015 Apr 22.
Abstract/Text OBJECTIVE: To build a prediction model that estimates the 3-year rupture risk of unruptured saccular cerebral aneurysms.
METHODS: Survival analysis was done using each aneurysm as the unit for analysis. Derivation data were from the Unruptured Cerebral Aneurysm Study (UCAS) in Japan. It consists of patients with unruptured cerebral aneurysms enrolled between 2000 and 2004 at neurosurgical departments at tertiary care hospitals in Japan. The model was presented as a scoring system, and aneurysms were classified into 4 risk grades by predicted 3-year rupture risk: I, < 1%; II, 1 to 3%; III, 3 to 9%, and IV, >9%. The discrimination property and calibration plot of the model were evaluated with external validation data. They were a combination of 3 Japanese cohort studies: UCAS II, the Small Unruptured Intracranial Aneurysm Verification study, and the study at Jikei University School of Medicine.
RESULTS: The derivation data include 6,606 unruptured cerebral aneurysms in 5,651 patients. During the 11,482 aneurysm-year follow-up period, 107 ruptures were observed. The predictors chosen for the scoring system were patient age, sex, and hypertension, along with aneurysm size, location, and the presence of a daughter sac. The 3-year risk of rupture ranged from <1% to >15% depending on the individual characteristics of patients and aneurysms. External validation indicated good discrimination and calibration properties.
INTERPRETATION: A simple scoring system that only needs easily available patient and aneurysmal information was constructed. This can be used in clinical decision making regarding management of unruptured cerebral aneurysms.

© 2015 American Neurological Association.
PMID 25753954  Ann Neurol. 2015 Jun;77(6):1050-9. doi: 10.1002/ana.244・・・
著者: Makoto Sonobe, Tomosato Yamazaki, Masahiro Yonekura, Haruhiko Kikuchi
雑誌名: Stroke. 2010 Sep;41(9):1969-77. doi: 10.1161/STROKEAHA.110.585059. Epub 2010 Jul 29.
Abstract/Text BACKGROUND AND PURPOSE: The natural history and optimal management of incidentally found small unruptured aneurysms <5 mm in size remain unclear. A prospective study was conducted to determine the optimal management for incidentally found small unruptured aneurysms.
METHODS: From September 2000 to January, 2004, 540 aneurysms (446 patients) were registered. Four hundred forty-eight unruptured aneurysms <5 mm in size (374 patients) have been followed up for a mean of 41.0 months (1306.5 person-years) to date. We calculated the average annual rupture rate of small unruptured aneurysms and also investigated risk factors that contribute to rupture and enlargement of these aneurysms.
RESULTS: The average annual risks of rupture associated with small unruptured aneurysms were 0.54% overall, 0.34% for single aneurysms, and 0.95% for multiple aneurysms. Patient <50 years of age (P=0.046; hazard ratio, 5.23; 95% CI, 1.03 to 26.52), aneurysm diameter of >or=4.0 mm (P=0.023; hazard ratio, 5.86; 95% CI, 1.27 to 26.95), hypertension (P=0.023; hazard ratio, 7.93; 95% CI, 1.33 to 47.42), and aneurysm multiplicity (P=0.0048; hazard ratio, 4.87; 95% CI, 1.62 to 14.65) were found to be significant predictive factors for rupture of small aneurysms.
CONCLUSIONS: The annual rupture rate associated with small unruptured aneurysms is quite low. Careful attention should be paid to the treatment indications for single-type unruptured aneurysms <5 mm. If the patient is <50 years of age, has hypertension, and multiple aneurysms with diameters of >or=4 mm, treatment should be considered to prevent future aneurysmal rupture.

PMID 20671254  Stroke. 2010 Sep;41(9):1969-77. doi: 10.1161/STROKEAHA.・・・
著者: T Horikoshi, A Fukamachi, H Nishi, I Fukasawa
雑誌名: Neuroradiology. 1994 Apr;36(3):203-7.
Abstract/Text The purpose of this study was to investigate the reliability of magnetic resonance angiography (MRA) for detection of intracranial aneurysms. Ninety-six consecutive patients who underwent both MRA using the three-dimensional time-of-flight technique (3D TOF) with the rephase/dephase subtraction method and conventional angiography were reviewed. MRA showed 22 aneurysms in 19 patients, and conventional angiography 28 aneurysms in 23 patients. The sensitivity of MRA was thus 79% for aneurysms in 83% of patients. MRA showed no aneurysm in 67 of 73 patients without aneurysms; its specificity was therefore 92%. The 6 false positive interpretations were suspected internal carotid artery aneurysms.

PMID 8041440  Neuroradiology. 1994 Apr;36(3):203-7.
著者: P M White, J M Wardlaw, V Easton
雑誌名: Radiology. 2000 Nov;217(2):361-70. doi: 10.1148/radiology.217.2.r00nv06361.
Abstract/Text PURPOSE: To perform a systematic review to determine the accuracy of computed tomographic (CT) angiography, magnetic resonance (MR) angiography, and transcranial Doppler ultrasonography (US) in depicting intracranial aneurysms.
MATERIALS AND METHODS: A 1988-1998 literature search for studies with 10 or more subjects in which noninvasive imaging was compared with angiography was undertaken. Studies meeting initial criteria were evaluated by using intrinsically weighted standardized assessment to determine suitability for inclusion. Studies scoring greater than 50% were included.
RESULTS: Of 103 studies that met initial criteria, 38 scored greater than 50%. CT angiography and MR angiography had accuracies per aneurysm of 89% (95% CI: 87%, 91%) and 90% (95% CI: 87%, 92%), respectively. For US, data were scanty and accuracy was lower, although the CIs overlapped those of CT angiography and MR angiography. Sensitivity was greater for detection of aneurysms larger than 3 mm than for detection of aneurysms 3 mm or smaller-for CT angiography, 96% (95% CI: 94%, 98%) versus 61% (95% CI: 51%, 70%), and for MR angiography, 94% (95% CI: 90%, 97%) versus 38% (95% CI: 25%, 53%). Diagnostic accuracy was similar for anterior and posterior circulation aneurysms.
CONCLUSION: CT angiography and MR angiography depicted aneurysms with an accuracy of about 90%. Most studies were performed in populations with high aneurysm prevalence, which may have introduced bias toward noninvasive examinations.

PMID 11058629  Radiology. 2000 Nov;217(2):361-70. doi: 10.1148/radiolo・・・
著者: Magnetic Resonance Angiography in Relatives of Patients with Subarachnoid Hemorrhage Study Group
雑誌名: N Engl J Med. 1999 Oct 28;341(18):1344-50. doi: 10.1056/NEJM199910283411803.
Abstract/Text BACKGROUND: The first-degree relatives of patients who have subarachnoid hemorrhage from ruptured intracranial aneurysms are themselves at risk for subarachnoid hemorrhage. We studied the benefits and risks of screening for aneurysms in the first-degree relatives of patients with sporadic subarachnoid hemorrhage.
METHODS: We screened 626 first-degree relatives (parents, siblings, or children) of 160 patients with sporadic subarachnoid hemorrhage, from a prospective series of 193 consecutive index patients. Magnetic resonance angiography was the screening tool, and conventional angiography was used as the reference test in subjects thought to have aneurysms. Six months after elective operation, outcome was assessed by means of the modified Rankin scale of neurologic function. This observational study design was combined with a decision-analysis model to estimate the effectiveness of screening. The efficiency of screening was defined by the number of relatives who needed to be screened in order to prevent one subarachnoid hemorrhage.
RESULTS: Aneurysms were found in 25 of 626 first-degree relatives (4.0 percent; 95 percent confidence interval, 2.6 to 5.8 percent). Eighteen underwent surgery, which resulted in a decrease in function in 11 (disabling in 1). Five had aneurysms that were 5 to 11 mm in diameter, 11 had aneurysms that were less than 5 mm, and 2 had both small and medium-sized aneurysms. On average, surgery increased estimated life expectancy by 2.5 years for these 18 subjects (or by 0.9 month per person screened), at the expense of 19 years of decreased function per person. The number of relatives who would need to be screened in order to prevent 1 subarachnoid hemorrhage on a lifetime basis was 149, and 298 would have to be screened in order to prevent 1 fatal subarachnoid hemorrhage.
CONCLUSIONS: Implementation of a screening program for the first-degree relatives of patients with sporadic subarachnoid hemorrhage does not seem warranted at this time, since the resulting slight increase in life expectancy does not offset the risk of postoperative sequelae.

PMID 10536126  N Engl J Med. 1999 Oct 28;341(18):1344-50. doi: 10.1056・・・
著者: Y Yoshimoto, S Wakai
雑誌名: Stroke. 1999 Aug;30(8):1621-7.
Abstract/Text BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) due to aneurysmal rupture is a major cause of cerebrovascular disease-related death. This problem could be eliminated by diagnosis and successful treatment of aneurysms before rupture. Recent developments in high-resolution imaging technology have made screening for unruptured aneurysms possible in the general population. Such screening has become widespread in Japan ("No Dokku, " or brain checkup). As a result, unruptured aneurysms are being identified with increasing frequency. However, the economic implications of treatment decisions for unruptured aneurysms have not been analyzed. Therefore, we performed such an analysis.
METHODS: We used a Markov model to evaluate the cost-effectiveness of screening for asymptomatic, unruptured intracranial aneurysms. The model involved a set of variables describing discrete health states. Each state was assigned a quality of life score and an associated medical cost. A comparison of the expected outcomes was then made between 2 hypothetical cohorts, one receiving screening and the other no screening. A sensitivity analysis was performed by altering the input values within clinically reasonable ranges to reflect uncertainty in the baseline analysis and then assessing the effects on outcomes.
RESULTS: Combining the incremental cost and effectiveness data revealed a cost per quality-adjusted life-year of $7760 for an annual rate of subarachnoid hemorrhage due to unruptured aneurysms (rupture rate) of 0.02; this cost was $39 450 for a rupture rate of 0.01. There was no benefit (negative quality-adjusted life-year benefit) for a rupture rate of 0.005, the rupture rate found in a recently published international cooperative study. The risks of surgery for unruptured aneurysms and the discounting ratio used to assess the impact of timing of costs and benefits on future outcomes also had significant effects on the results. Other variables had little impact on cost-effectiveness.
CONCLUSIONS: The cost-effectiveness of screening for an unruptured aneurysm is highly sensitive to the annual rate of subarachnoid hemorrhage due to unruptured aneurysms. The low annual rupture rate seen in the recent large international cooperative study implies that screening asymptomatic populations to identify and treat unruptured aneurysms would not be cost cost-effective.

PMID 10436111  Stroke. 1999 Aug;30(8):1621-7.
著者: P Mitchell, I D Wilkinson, N Hoggard, M N Paley, D A Jellinek, T Powell, C Romanowski, T Hodgson, P D Griffiths
雑誌名: J Neurol Neurosurg Psychiatry. 2001 Feb;70(2):205-11.
Abstract/Text OBJECTIVES: To measure the sensitivity and specificity of five MRI sequences to subarachnoid haemorrhage.
METHODS: Forty one patients presenting with histories suspicious of subarachnoid haemorrhage (SAH) were investigated with MRI using T1 weighted, T2 weighted, single shot fast spin echo (express), fluid attenuation inversion recovery (FLAIR), and gradient echo T2* sequences, and also by CT. Lumbar puncture was performed in cases where CT was negative for SAH. Cases were divided into acute (scanned within 4 days of the haemorrhage) and subacute (scanned after 4 days) groups.
RESULTS: The gradient echo T2* was the most sensitive sequence, with sensitivities of 94% in the acute phase and 100% in the subacute phase. Next most sensitive was FLAIR with values of 81% and 87% for the acute and subacute phases respectively. Other sequences were considerably less sensitive.
CONCLUSIONS: MRI can be used to detect subacute and acute subarachnoid haemorrhage and has significant advantages over CT in the detection of subacute subarachnoid haemorrhage. The most sensitive sequence was the gradient echo T2*.

PMID 11160469  J Neurol Neurosurg Psychiatry. 2001 Feb;70(2):205-11.
著者: T Ogawa, A Inugami, E Shimosegawa, H Fujita, H Ito, H Toyoshima, S Sugawara, I Kanno, T Okudera, K Uemura
雑誌名: Radiology. 1993 Feb;186(2):345-51. doi: 10.1148/radiology.186.2.8421732.
Abstract/Text Thirty-seven magnetic resonance (MR) examinations were performed at 0.5 T in 33 patients with subarachnoid hemorrhage (SAH) caused by a ruptured aneurysm. Images were obtained 2 hours to 75 days after the ictus. Twenty-four proton-density-weighted (long repetition time [TR], short echo time [TE]) images were obtained in the acute stage (< 72 hours after the ictus) of SAH; SAH was hyperintense to brain parenchyma and cerebrospinal fluid in all cases. The detectability of acute SAH on T1- (short TR, short TE) and T2- (long TR, long TE) weighted images was 36% and 50%, respectively. In the subacute and chronic stages (> 3 days after the ictus), the detectability of SAH on T1-, T2-, and proton-density-weighted images was 73%, 31%, and 83%, respectively. Although computed tomography is still the modality of choice for evaluating acute SAH, the authors emphasize that even acute SAH can be reliably demonstrated with MR imaging with the appropriate parameters.

PMID 8421732  Radiology. 1993 Feb;186(2):345-51. doi: 10.1148/radiolo・・・
著者: Irene C van der Schaaf, Eva H Brilstra, Gabriel J E Rinkel, Patrick M Bossuyt, J van Gijn
雑誌名: Stroke. 2002 Feb;33(2):440-3.
Abstract/Text BACKGROUND AND PURPOSE: The objective of this study was to assess the health-related quality of life and symptoms of anxiety and depression in patients who are aware of the presence of a patent aneurysm or arteriovenous malformation.
METHODS: Participants were retrospectively identified and invited to participate in the study; consenting participants were interviewed in a face-to-face setting by means of 2 questionnaires assessing health-related quality of life (Sickness Impact Profile [SIP] and the MOS Short Form-36 [SF-36]) and psychological state (Hospital Anxiety and Depression Scale [HADS]). We used Student's t test statistics to compare the scores of the study population with the scores of reference populations.
RESULTS: We identified 21 patients, of whom 9 had an aneurysm and 12 had an arteriovenous malformation. Compared with the reference population, these patients had a reduced quality of life for sleep and rest (difference of SIP means, 6.8; 95% CI, 3.1 to 10.5), emotional behavior (10.1; 95% CI, 5.7 to 14.6), mobility (5.4; 95% CI, 2.1 to 8.7), social interactions (5.3; 95% CI, 1.6 to 8.9), and alertness behavior (11.9; 95% CI, 6.2 to 17.5). The SIP psychosocial subscore (7.1; 95% CI, 3.9 to 10.2) and total SIP score (4.7; 95% CI, 2.2 to 7.2) were also significantly impaired. For the SF-36 domains, social functioning was significantly decreased compared with the reference population (8.9; 95% CI, 0.1 to 17.7). HADS scores for depression were similar for patients and the reference population.
CONCLUSIONS: Our study shows that knowledge of harboring an unoccluded untreated intracranial aneurysm or arteriovenous malformation reduces quality of life, most prominently on the psychosocial domains, without leading to substantially raised levels of anxiety and depression.

PMID 11823649  Stroke. 2002 Feb;33(2):440-3.
著者: I C van der Schaaf, M J H Wermer, B K Velthuis, E Buskens, P M M Bossuyt, G J E Rinkel
雑誌名: J Neurol Neurosurg Psychiatry. 2006 Jun;77(6):748-52. doi: 10.1136/jnnp.2005.079194.
Abstract/Text OBJECTIVES: In patients with previous subarachnoid haemorrhage (SAH) undergoing follow up screening, the authors assessed the impact of finding but not treating very small aneurysms by comparing quality of life (QOL), anxiety, and depression between patients with a newly detected aneurysm that was left untreated (cases) and patients with a negative screening (controls) as this should be incorporated in the evaluation of effectiveness of screening.
METHODS: In patients with previous SAH undergoing screening for new aneurysms the authors compared QOL (SF-36, EURO-QOL, and a screening related questionnaire), anxiety, and depression (Hospital Anxiety and Depression Scale (HADS)) between cases and controls. Differences in scores on the SF-36, EURO-QOL, and HADS were assessed with Student's t test and differences in proportions of patients with HADS scores in the pathological range and screening related changes with chi2 analysis. The authors powered the study to detect a moderate, clinically relevant difference.
RESULTS: Thirty five cases and 34 controls were included. Trends for health related QOL, anxiety, depression, and consequences in daily life pointed in the same direction of a less favourable situation for cases but all effects were small, and did not reach statistical significance. On the screenings specific questionnaire, cases more often (but not statistically significant) reported changes in daily life.
CONCLUSIONS: The authors found no major or moderate impact on QOL, anxiety, and depression of the awareness of having an untreated aneurysm, which was detected at screening, although most items showed a trend towards more negative effects for cases. Minor effects on individual level cannot be excluded by this study.

PMID 16705198  J Neurol Neurosurg Psychiatry. 2006 Jun;77(6):748-52. d・・・
著者: J T King, H Yonas, M B Horowitz, A B Kassam, M S Roberts
雑誌名: J Neurol Neurosurg Psychiatry. 2005 Apr;76(4):550-4. doi: 10.1136/jnnp.2004.051649.
Abstract/Text OBJECTIVE: To assess communication between vascular neurosurgeons and their patients with unruptured cerebral aneurysms about treatment options and expected outcomes.
METHODS: Vascular neurosurgeons and their patients with cerebral aneurysms were surveyed immediately following outpatient appointments in a neurosurgery clinic. Data collected included how well the patient understood their aneurysm treatment options, the risks of a poor outcome from various treatments, and the consensus "best" treatment. Patient and neurosurgeon responses were measured using Likert scales, multiple choice questions, and visual analogue scales. Agreement between patient and neurosurgeon was assessed with kappa scores. The Wilcoxon sign rank test was used to compare visual analogue scale responses.
RESULTS: Data for 44 patient-neurosurgeon pairs were collected. Only 61% of patient-neurosurgeon pairs agreed on the best treatment plan for the patient's aneurysm (kappa = 0.51, moderate agreement). Among the neurosurgeons, agreement with their patients ranged from 82% (kappa = 0.77, almost perfect agreement) to 52% (kappa = 0.37, fair agreement). Patients estimated much higher risks of stroke or death from surgical clipping, endovascular embolisation, or no intervention compared with the estimates offered by their neurosurgeons (surgical clipping: patient 36% v neurosurgeon 13%, p<0.001; endovascular embolisation: patient 35% v neurosurgeon 19%, p = 0.040; and no
INTERVENTION: patient 63% v neurosurgeon 25%, p<0.001).
CONCLUSIONS: Following consultation with a vascular neurosurgeon, many patients with cerebral aneurysms have an inaccurate understanding of their aneurysm treatment plan and an exaggerated sense of the risks of aneurysmal disease and treatment.

PMID 15774444  J Neurol Neurosurg Psychiatry. 2005 Apr;76(4):550-4. do・・・
著者: Yasunari Otawara, Kuniaki Ogasawara, Yoshitaka Kubo, Nobuhiko Tomitsuka, Mikio Watanabe, Akira Ogawa, Michiyasu Suzuki, Keiko Yamadate
雑誌名: Surg Neurol. 2004 Jul;62(1):28-31; discussion 31. doi: 10.1016/j.surneu.2003.07.012.
Abstract/Text BACKGROUND: Ruptured intracranial aneurysm is a serious condition with high mortality and morbidity. Patients notified of the presence of the unruptured intracranial aneurysm may become anxious because of the fear of rupture. We prospectively investigated the anxiety of patients with unruptured intracranial aneurysm before and after surgery.
METHODS: Thirty-seven patients with an asymptomatic unruptured intracranial aneurysm were enrolled, 13 men and 24 women aged 32 to 70 years (mean age, 57.2 years), who underwent surgical repair of the aneurysm. The anxiety of patients was assessed one month before and after surgery using the Japanese version of the State-Trait Anxiety Inventory.
RESULTS: The trait anxiety scores, which refer to stable personality factors reflecting the general level of fearfulness, did not change significantly after surgery. In contrast, the state anxiety scores, which refer to transient anxiety that varies according to the situation, decreased significantly after surgery (p = 0.001, paired t test). Only the preoperative high state anxiety scores among the multiple variables were associated with the significant decrease in state anxiety after surgery (p = 0.0183, logistic regression analysis).
CONCLUSIONS: The anxiety of patients with asymptomatic unruptured intracranial aneurysm significantly decreased after surgery. Anxiety of patients with asymptomatic unruptured intracranial aneurysm may deserve attention in deciding whether to treat the aneurysm.

PMID 15226063  Surg Neurol. 2004 Jul;62(1):28-31; discussion 31. doi: ・・・
著者: Akio Morita
雑誌名: Rinsho Shinkeigaku. 2002 Nov;42(11):1188-90.
Abstract/Text Information technology has been introduced in the medical field recently, and has become an essential tool for medical research in many aspects. Japanese Neurosurgical Society has been conducting a national study on the outcome of unruptured cerebral aneurysms (UCA) using on-line registration system. In this report, the author reports preliminary outcome of this study and discuss the usefulness and limits of studies using such technology. This study is a prospective cohort study and enrolled patients are cases with newly diagnosed UCA after Jan. 1,2001. So far, we have collected data of 2979 new patients (3667 aneurysms) with UCA registered from 385 institutions. Seventy five percent of the institutions sent data through the online registration. On-line registration system made data collection from all over the country very quick and easy. Analyzing such data could be achieved with minimal cost and time. Such study design can eliminate the handicap of geographic distance and can be applied for international studies. On the other hand, such system does not suit complicated study or rare disease. And On-line study design requires special consideration on various scenario and uniformity in assessing inclusion, procedure and outcome.

PMID 12784702  Rinsho Shinkeigaku. 2002 Nov;42(11):1188-90.
著者: F P Wirth, E R Laws, D Piepgras, R M Scott
雑誌名: Neurosurgery. 1983 May;12(5):507-11. doi: 10.1227/00006123-198305000-00005.
Abstract/Text A 6-year retrospective analysis of incidental intracranial aneurysm surgery was conducted at 12 medical centers (1975-1981). The surgical facilities and techniques were comparable at the institutions surveyed. From a total of 1671 aneurysms operated upon, 119 in 107 patients were unruptured and were discovered incidentally. Among these 107 patients, there was no operative mortality. Operative morbidity occurred in 7 cases (6.5%). Surgical treatment of large aneurysms in less accessible locations incurred the greatest operative morbidity. Presenting symptoms of cerebral ischemia seemed to be associated with increased operative morbidity, whereas repair of aneurysms incidental to other ruptured aneurysms had a uniformly low morbidity. These surgical results compare favorably with the risks of hemorrhage from unruptured intracranial aneurysms as defined by recent reports. The low morbidity without mortality supports a recommendation for surgical management of incidental aneurysms in the anterior circulation at centers equipped for modern aneurysm surgery.

PMID 6866231  Neurosurgery. 1983 May;12(5):507-11. doi: 10.1227/00006・・・
著者: T W Raaymakers, G J Rinkel, M Limburg, A Algra
雑誌名: Stroke. 1998 Aug;29(8):1531-8.
Abstract/Text BACKGROUND AND PURPOSE: Greater availability and improvement of neuroradiological techniques have resulted in more frequent detection of unruptured aneurysms. Because prognosis of subarachnoid hemorrhage is still poor, preventive surgery is increasingly considered as a therapeutic option. Elective surgery requires reliable data on its risks. Therefore, we performed a meta-analysis on the mortality and morbidity of surgery for unruptured intracranial aneurysms.
METHODS: Through Medline and additional searches by hand, we retrieved studies on clipping of unruptured (additional, symptomatic, or incidental) aneurysms published from 1966 through June 1996. Two authors independently extracted data. We used weighted linear regression for data analysis.
RESULTS: We included 61 studies that involved 2460 patients (57% female; mean age, 50 years) and at least 2568 unruptured aneurysms (27% >25 mm, 30% located in the posterior circulation). Mortality was 2.6% (95% confidence interval [CI], 2.0% to 3.3%). Permanent morbidity occurred in 10.9% (95% CI, 9.6% to 12.2%) of patients. Postoperative mortality was significantly lower in more recent years for nongiant aneurysms and aneurysms with an anterior location; the last 2 characteristics were also associated with a significantly lower morbidity.
CONCLUSIONS: In studies published between 1966 and 1996 on clipping of unruptured aneurysms, mortality was 2.6% and morbidity was 10.9%. In calculating the pros and cons of preventive surgery, these proportions should be taken into account.

PMID 9707188  Stroke. 1998 Aug;29(8):1531-8.
著者: J T King, H A Glick, T J Mason, E S Flamm
雑誌名: J Neurosurg. 1995 Sep;83(3):403-12. doi: 10.3171/jns.1995.83.3.0403.
Abstract/Text Cost-effectiveness analysis uses both economic and clinical outcomes data to evaluate treatment options. In this era of economic constraints on health care, treatments that are not cost-effective will increasingly be denied public and private insurance reimbursement. The authors used mathematical modeling techniques to assess the cost-effectiveness of elective surgery for the treatment of asymptomatic, unruptured, intracranial aneurysms. Input values for the Markov model used in this study were determined from both the literature and clinical judgment. Direct medical costs for hospitalization and physician fees were derived from Medicare cost reports and resource-based relative-value units, expressed in 1992 U.S. dollars. Costs and benefits were discounted at an annual rate of 5%. Using baseline model assumptions for a 50-year-old patient, elective aneurysm surgery provides an average of 0.88 additional quality-adjusted life years (QALYs) compared with nonsurgical treatment. However, prompt elective surgery ($23,300) costs more than expectant management ($2100), in which only patients whose aneurysms rupture incur treatment costs. Combining the outcomes and cost data, the incremental cost-effectiveness of elective aneurysm surgery is $24,200 per QALY, which is comparable to other accepted medical or surgical interventions, such as total knee arthroplasty ($15,200/QALY) or antihypertensive therapy in a 50-year-old patient ($29,800/QALY). Prompt elective surgery for asymptomatic, unruptured, intracranial aneurysms is recommended as a cost-effective use of medical resources provided: 1) surgical morbidity and mortality remain at reported levels; 2) the patient has a life expectancy of at least 13 additional years; and 3) the patient experiences a decrease in quality of life from knowingly living with an unruptured aneurysm.

PMID 7666214  J Neurosurg. 1995 Sep;83(3):403-12. doi: 10.3171/jns.19・・・
著者: Yasunari Otawara, Kuniaki Ogasawara, Akira Ogawa, Keiko Yamadate
雑誌名: Stroke. 2005 Jan;36(1):142-3. doi: 10.1161/01.STR.0000149925.36914.4e. Epub 2004 Nov 29.
Abstract/Text BACKGROUND AND PURPOSE: This prospective study investigated whether surgery for unruptured intracranial aneurysms (UIAs) affects cognitive function and cerebral blood flow (CBF).
METHODS: Cognitive tests using the Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale, Rey-Osterrieth Complex Figure test, and CBF measurements using single-photon emission computed tomography were performed before and after surgery for UIAs in 44 patients < or =70 years of age.
RESULTS: Group-rate analysis showed the verbal intelligence quotient (IQ), performance IQ, full-scale IQ, and recall trial scores of the Rey-Osterrieth Complex Figure test all increased significantly after surgery, whereas the Wechsler Memory Scale and copy trial scores of the Rey-Osterrieth Complex Figure test were not significantly different. Event-rate analysis demonstrated that no patient showed impaired cognition. There was no significant difference between CBF before and after surgery.
CONCLUSIONS: Surgical repair for UIAs does not impair cognition or CBF in patients without postoperative restrictions in lifestyle.

PMID 15569864  Stroke. 2005 Jan;36(1):142-3. doi: 10.1161/01.STR.00001・・・
著者: T W Raaymakers
雑誌名: J Neurol Neurosurg Psychiatry. 2000 May;68(5):571-6.
Abstract/Text OBJECTIVES: To assess outcome after elective treatment for unruptured intracranial aneurysms.
METHODS: Of 193 consecutive patients with subarachnoid haemorrhage 626 first degree relatives (parents, siblings, children) were screened with magnetic resonance angiography. Subsequently, 18 relatives underwent elective angiography and operation. Outcome was assessed in terms of impairments (neurological examination), disabilities (Barthel index), handicaps (Rankin scale), and quality of life (sickness impact profile (SIP) and short form-36 (SF-36)) 3 months and 1 year after operation; it was compared with baseline measurements.
RESULTS: Before angiography all patients had a normal neurological examination, optimal Barthel and Rankin scores, and a quality of life similar to that in a reference population. Three months postoperatively five patients (28%; 95% confidence interval (95% CI) 10-54%) had neurological impairments (one after angiography), two (11%; 95% CI 1-35%) had a decrease in Barthel index, and 15 (83%; 95% CI 59-96%) had suboptimal Rankin scores (none was dependent in daily living). Quality of life (SIP and SF-36) was reduced for most domains. After 1 year, five patients still had neurological impairments, all had an optimal Barthel index, and eight (47%; 95% CI 23-72%) had suboptimal Rankin scores. Quality of life returned to baseline levels for all SIP and most SF-36 domains.
CONCLUSIONS: Treatment of unruptured aneurysms has a considerable short term negative impact on functional health and quality of life in most patients, despite the low rate of impairments. Outcome improves markedly but not completely within 1 year after operation.

PMID 10766885  J Neurol Neurosurg Psychiatry. 2000 May;68(5):571-6.
著者: Eva H Brilstra, Gabriel J E Rinkel, Yolanda van der Graaf, Menno Sluzewski, Rob J Groen, Rob T H Lo, Cornelis A F Tulleken
雑誌名: Cerebrovasc Dis. 2004;17(1):44-52. doi: 10.1159/000073897. Epub 2003 Oct 3.
Abstract/Text BACKGROUND: Relatively high rates of complications occur after operation for unruptured intracranial aneurysms. Published data on endovascular treatment suggest lower rates of complications. We measured the impact of treatment of unruptured aneurysms by clipping or coiling on functional health, quality of life, and the level of anxiety and depression.
METHODS: In three centres, we prospectively collected data on patients with an unruptured aneurysm who were treated by clipping or coiling. Treatment assignment was left to the discretion of the treating physicians. Before, 3 and 12 months after treatment, we used standardised questionnaires to assess functional health (Rankin Scale score), quality of life (SF-36, EuroQol), and the level of anxiety and depression (Hospital Anxiety and Depression Scale).
RESULTS: Nineteen patients were treated by coiling and 32 by clipping. In the surgical group, 4 patients (12%) had a permanent complication; 36 of all 37 aneurysms (97%) were successfully clipped. Three months after operation, quality of life was worse than before operation; 12 months after operation, it had improved but had not completely returned to baseline levels. Scores for depression were higher than in the general population. In the endovascular group, no complications with permanent deficits occurred; 16 of 19 aneurysms (84%) were occluded by more than 90%. One patient died from rupture of the previously coiled aneurysm. In the others, quality of life after 3 months and after 1 year was similar to that before treatment.
CONCLUSIONS: In the short term, operation of patients with an unruptured aneurysm has a considerable impact on functional health and quality of life. After 1 year, recovery occurs but it is incomplete. Coil embolisation does not affect functional health and quality of life.

Copyright 2004 S. Karger AG, Basel
PMID 14530637  Cerebrovasc Dis. 2004;17(1):44-52. doi: 10.1159/0000738・・・
著者: Shigeo Yamashiro, Toru Nishi, Kazunari Koga, Tomoaki Goto, Masatomo Kaji, Daisuke Muta, Jun-ichi Kuratsu, Shodo Fujioka
雑誌名: J Neurol Neurosurg Psychiatry. 2007 May;78(5):497-500. doi: 10.1136/jnnp.2006.098871. Epub 2006 Dec 18.
Abstract/Text OBJECTIVE: To compare the preoperative and postoperative health-related quality of life (QOL) and psychological state of patients with asymptomatic unruptured intracranial aneurysms (ICAs) who underwent elective surgery.
METHODS: Out of 67 patients who underwent neck clipping of ICAs, we assessed the QOL of 61 patients using Short Form-36 (SF-36); their psychological state was rated on the Hospital Anxiety and Depression Scale (HADS) before, 3 months, and 1 and 3 years after treatment.
RESULTS: The preoperative mean scores for each of the eight SF-36 domains except bodily pain were significantly lower in the study population than in the reference population. 14 (20.9%) patients experienced surgical complications defined as neurological deterioration and/or abnormal CT findings within 30 days of the operation. Despite some complications, the QOL of all operated patients returned to the mean level of the reference population 3 years after treatment. At 3 months after surgery, the scores for psychosocial activities and general health perception were transiently below the preoperative levels. According to the HADS, the patients experienced mild anxiety before the operation; it disappeared by the third postoperative month.
CONCLUSIONS: Preoperatively, patients with unruptured ICAs reported a significantly decreased QOL. It further declined transiently after elective surgery, but it returned to the mean level recorded for the reference population within 3 years. Our findings suggest that these patients derived significant QOL benefits from their surgery. Hence subjective QOL issues should be considered in deciding whether treatment-related risks and their natural history, such as their potential rupture, warrant surgery of asymptomatic unruptured ICAs.

PMID 17178825  J Neurol Neurosurg Psychiatry. 2007 May;78(5):497-500. ・・・
著者: John Thornton, Gerard M Debrun, Victor A Aletich, Qasim Bashir, Fady T Charbel, James Ausman
雑誌名: Neurosurgery. 2002 Feb;50(2):239-49; discussion 249-50.
Abstract/Text OBJECTIVE: The success of endovascular treatment of intracranial aneurysms with Guglielmi detachable coils (GDCs) is dependent on the long-term exclusion of the aneurysm from the circulation. We reviewed our experience with the long-term angiographic follow-up monitoring of aneurysms that had been treated with GDCs.
METHODS: All patients whose aneurysms had been treated with GDCs between January 1995 and August 1999 and who subsequently underwent follow-up angiography at 6 months or more were included in this study. We reviewed all of the angiographic findings, to determine the percentage of aneurysm occlusion on the initial angiograms and on the last available follow-up angiograms. The categories of aneurysm occlusion used were 100%, >or=95%, and less than 95% occlusion.
RESULTS: One hundred thirty patients with 141 aneurysms underwent 143 endovascular coiling procedures and subsequently underwent angiographic follow-up monitoring of 6 months or more. There were 102 female and 28 male patients. The mean angiographic follow-up period was 16.7 months (range, 6-62 mo). The initial rates of occlusion were 100% for 56 aneurysms (39%), >or=95% for 65 aneurysms (46%), and less than 95% for 22 aneurysms (15%). Recurrence of one aneurysm (1.8%) was observed. Of the 87 aneurysms that were incompletely occluded initially, there was progressive thrombosis in 40 (46%), stable neck remnants in 23 (26%), and enlargement of the residual neck in 24 (28%). The final occlusion rates, determined on the last available angiograms, were 100% for 88 aneurysms (61%), >or=95% for 31 aneurysms (22%), and less than 95% for 24 aneurysms (17%). No patient experienced repeat or new subarachnoid hemorrhage more than 6 months after the initial treatment.
CONCLUSION: Late angiographic follow-up monitoring of aneurysms that have been treated with GDCs demonstrates the durability of the treatment. Aneurysms with large residual neck remnants were subjected to further treatment, whereas aneurysms with small residual neck remnants remain under observation.

PMID 11844258  Neurosurgery. 2002 Feb;50(2):239-49; discussion 249-50.・・・
著者: Jean-Philippe Cottier, Aurore Bleuzen-Couthon, Sophie Gallas, Catherine B Vinikoff-Sonier, Philippe Bertrand, Florence Domengie, Laurent Barantin, Denis Herbreteau
雑誌名: AJNR Am J Neuroradiol. 2003 Oct;24(9):1797-803.
Abstract/Text BACKGROUND AND PURPOSE: Three-dimensional time-of-flight (TOF) MR angiography has been evaluated in the follow-up of intracranial aneurysms treated with Guglielmi detachable coils (GDCs) with good results. Some of the studies used contrast material in addition to the 3D TOF MR technique and others did not. We assessed the usefulness of contrast material with 3D TOF MR angiography by comparing this sequence before and after contrast material injection.
METHODS: Fifty-eight patients harboring a total of 71 cerebral aneurysms previously treated with GDCs were included in the prospective study. MR angiography (at 1.5 T) was performed with a 3D TOF sequence before and after injection of gadolinium-based contrast material. Features evaluated were presence and size of a neck remnant, parent and adjacent vessel patency, and venous overlap. Digital subtraction angiography was the standard of reference.
RESULTS: Comparison of the techniques showed a good agreement in the detection of residual flow. Six cases of small residual neck were not detected with either the 3D TOF or the contrast-enhanced 3D TOF sequence. In one case of giant aneurysm, the extent of recanalization was more evident after contrast material administration. The use of contrast material did not help to show the parent and adjacent arteries. Venous overlap on contrast-enhanced 3D TOF angiograms did not affect image interpretation.
CONCLUSION: In this series, the use of intravenous contrast material did not improve the ability of 3D TOF MR angiography to depict the presence of residual or recurrent aneurysms previously treated with endovascular coiling. In one giant aneurysm, use of intravenous contrast material did result in improved visualization of a residual aneurysm.

PMID 14561605  AJNR Am J Neuroradiol. 2003 Oct;24(9):1797-803.
著者: Mike Clarke
雑誌名: Neuroradiology. 2008 Aug;50(8):653-64. doi: 10.1007/s00234-008-0411-9. Epub 2008 Jun 17.
Abstract/Text Systematic reviews of systematic reviews identify good quality reviews of earlier studies of medical conditions. This article describes a systematic review of systematic reviews performed to investigate factors that might influence the risk of rupture of an intracranial aneurysm. It exemplifies the technique of this type of research and reports the finding of a specific study. The annual incidence of subarachnoid haemorrhage resulting from the rupture of intracranial aneurysms is estimated to be nine per 100,000. A large proportion of people who have this bleed, will die or remain dependent on the care of others for some time. Reliable knowledge about the risks of subarachnoid haemorrhage in different populations will help in planning, screening and prevention strategies and in predicting the prognosis of individual patients. If the necessary data were available in the identified reviews, an estimate for the numerical relationship between a particular characteristic and the risk of subarachnoid haemorrhage was included in this report. The identification of eligible systematic reviews relied mainly on the two major bibliographic databases of the biomedical literature: PubMed and EMBASE. These were searched in 2006, using specially designed search strategies. Approximately 2,000 records were retrieved and each of these was checked carefully against the eligibility criteria for this systematic review. These criteria required that the report be a systematic review of studies assessing the risk of subarachnoid haemorrhage in patients known to have an unruptured intracranial aneurysm or of studies that had investigated the characteristics of people who experienced a subarachnoid haemorrhage without previously being known to have an unruptured aneurysm. Reports which included more than one systematic review were eligible and each of these reviews was potentially eligible. The quality of each systematic review was assessed. In this review, 16 separate reports were identified, including a total of 46 eligible systematic reviews. These brought together research studies for 24 different risk factors. This has shown that the following factors appear to be associated with a higher risk of subarachnoid haemorrhage: being a woman, older age, posterior circulation aneurysms, larger aneurysms, previous symptoms, "non-white" ethnicity, hypertension, low body mass index, smoking and alcohol consumption of more than 150 g per week. The following factors appear to be associated with a lower risk of subarachnoid haemorrhage: high cholesterol, diabetes and use of hormone replacement therapy.

PMID 18560819  Neuroradiology. 2008 Aug;50(8):653-64. doi: 10.1007/s00・・・
著者: Andrew Molyneux, Richard Kerr, Irene Stratton, Peter Sandercock, Mike Clarke, Julia Shrimpton, Rury Holman, International Subarachnoid Aneurysm Trial (ISAT) Collaborative Group
雑誌名: Lancet. 2002 Oct 26;360(9342):1267-74.
Abstract/Text BACKGROUND: Endovascular detachable coil treatment is being increasingly used as an alternative to craniotomy and clipping for some ruptured intracranial aneurysms, although the relative benefits of these two approaches have yet to be established. We undertook a randomised, multicentre trial to compare the safety and efficacy of endovascular coiling with standard neurosurgical clipping for such aneurysms judged to be suitable for both treatments.
METHODS: We enrolled 2143 patients with ruptured intracranial aneurysms and randomly assigned them to neurosurgical clipping (n=1070) or endovascular treatment by detachable platinum coils (n=1073). Clinical outcomes were assessed at 2 months and at 1 year with interim ascertainment of rebleeds and death. The primary outcome was the proportion of patients with a modified Rankin scale score of 3-6 (dependency or death) at 1 year. Trial recruitment was stopped by the steering committee after a planned interim analysis. Analysis was per protocol.
FINDINGS: 190 of 801 (23.7%) patients allocated endovascular treatment were dependent or dead at 1 year compared with 243 of 793 (30.6%) allocated neurosurgical treatment (p=0.0019). The relative and absolute risk reductions in dependency or death after allocation to an endovascular versus neurosurgical treatment were 22.6% (95% CI 8.9-34.2) and 6.9% (2.5-11.3), respectively. The risk of rebleeding from the ruptured aneurysm after 1 year was two per 1276 and zero per 1081 patient-years for patients allocated endovascular and neurosurgical treatment, respectively.
INTERPRETATION: In patients with a ruptured intracranial aneurysm, for which endovascular coiling and neurosurgical clipping are therapeutic options, the outcome in terms of survival free of disability at 1 year is significantly better with endovascular coiling. The data available to date suggest that the long-term risks of further bleeding from the treated aneurysm are low with either therapy, although somewhat more frequent with endovascular coiling.

PMID 12414200  Lancet. 2002 Oct 26;360(9342):1267-74.
著者: H E Westerlaan, A M van der Vliet, J M Hew, L C Meiners, J D M Metzemaekers, J J A Mooij, M Oudkerk
雑誌名: Neuroradiology. 2005 Aug;47(8):622-9. doi: 10.1007/s00234-005-1395-3. Epub 2005 Jun 28.
Abstract/Text The purpose of this study was to evaluate time-of-flight magnetic resonance angiography (MRA) in the follow-up of intracranial aneurysms treated with Guglielmi detachable coils (GDCs). From January 1998 to January 2002 27 MRA and intra-arterial digital subtraction angiography (IADSA) examinations were analyzed for residual aneurysms and arterial patency following GDC placement. A total number of 33 intracranial aneurysms was analyzed, including 18 located in the posterior circulation. The MRA analysis was based on source images in combination with maximum intensity projections. The IADSA was used as the reference standard. Two aneurysms were excluded from evaluation, because of susceptibility artefacts from other aneurysms, which were clipped. Sensitivity and positive predictive values of MRA in revealing residual aneurysms were, respectively, 89% and 80%. Specificity in ruling out remnant necks and residual flow around coils was, respectively, 91% and 97%, with a negative predictive value of, respectively, 95% and 100%. Specificity and negative predictive value of MRA for arterial occlusion were, respectively, 87% and 100% for the parent arteries and, respectively, 85% and 100% for the adjacent arteries. MRA is a reliable diagnostic tool in the follow-up of GDC treatment, and it may replace IADSA in excluding residual flow around coils and aneurysmal necks and in ruling out arterial occlusion.

PMID 15983772  Neuroradiology. 2005 Aug;47(8):622-9. doi: 10.1007/s002・・・
著者: J P Cottier, A Bleuzen-Couthon, S Gallas, C B Vinikoff-Sonier, P Bertrand, F Domengie, L Barantin, D Herbreteau
雑誌名: Neuroradiology. 2003 Nov;45(11):818-24. doi: 10.1007/s00234-003-1109-7. Epub 2003 Oct 8.
Abstract/Text All patients with aneurysms treated with Guglielmi detachable coils (GDC) are undergo angiography to assess long-term stability of aneurysm exclusion or to show recurrence of the aneurysm sac, which may require further treatment. We prospectively compared the plain-film appearance of the coil-mass, 3D time-of-flight MR angiography (TOF MRA) and digital subtraction angiography (DSA) for the detection of aneurysm recanalisation during follow-up. We studied 60 patients with 74 intracranial aneurysms treated with Guglielmi detachable coils. We used the unsubtracted image of the angiograms performed at the completion of any embolisation procedure and at follow-up as the plain radiographs. Recanalisation was considered if loosening, compaction or reorientation of the coil mass was apparent. TOF MRA was performed to assess the presence and size of a neck remnant. DSA was regarded as the definitive investigation. Comparison of the techniques showed good agreement as regards aneurysm recanalisation. MRA was more accurate than plain radiography and could replace DSA for long term follow- up. The initial follow-up examination should, however, include both modalities. In cases of contraindications or limitations to MRA, the interval between follow-up angiographic examinations could be increased if there is no change in the plain-film coil-mass appearances.

PMID 14534768  Neuroradiology. 2003 Nov;45(11):818-24. doi: 10.1007/s0・・・
著者: Jean Raymond, François Guilbert, Alain Weill, Stavros A Georganos, Louis Juravsky, Anick Lambert, Julie Lamoureux, Miguel Chagnon, Daniel Roy
雑誌名: Stroke. 2003 Jun;34(6):1398-403. doi: 10.1161/01.STR.0000073841.88563.E9. Epub 2003 May 29.
Abstract/Text BACKGROUND AND PURPOSE: Our aim in this study was to assess the incidence and determining factors of angiographic recurrences after endovascular treatment of aneurysms.
METHODS: A retrospective analysis of all patients with selective endosaccular coil occlusion of intracranial aneurysms prospectively collected from 1992 to 2002 was performed. There were 501 aneurysms in 466 patients (mean+/-SD age, 54.20+/-12.54 years; 74% female). Aneurysms were acutely ruptured (54.1%) or unruptured (45.9%). Mean+/-SD aneurysm size was 9.67+/-5.91 mm with a 4.31+/-1.97-mm neck. The most frequent sites were basilar bifurcation (27.7%) and carotid ophthalmic (18.0%) aneurysms. Recurrences were subjectively divided into minor and major (ideally necessitating re-treatment). The most significant predictors of angiographic recurrence were determined by logistic regression. These results were confirmed by chi2, t tests, or ANOVAs followed, when appropriate, by Tukey's contrasts.
RESULTS: Short-term (< or =1 year) follow-up angiograms were available in 353 aneurysms (70.5%) and long-term (>1 year) follow-up angiograms, in 277 (55%), for a total of 383 (76.5%) followed up. Recurrences were found in 33.6% of treated aneurysms that were followed up and that appeared at a mean+/-SD time of 12.31+/-11.33 months after treatment. Major recurrences presented in 20.7% and appeared at a mean of 16.49+/-15.93 months. Three patients (0.8%) bled during a mean clinical follow-up period of 31.32+/-24.96 months. Variables determined to be significant predictors (P<0.05) of a recurrence included aneurysm size > or =10 mm, treatment during the acute phase of rupture, incomplete initial occlusions, and duration of follow-up.
CONCLUSIONS: Long-term monitoring of patients treated by endosaccular coiling is mandatory.

PMID 12775880  Stroke. 2003 Jun;34(6):1398-403. doi: 10.1161/01.STR.00・・・
著者: Yuichi Murayama, Yih Lin Nien, Gary Duckwiler, Y Pierre Gobin, Reza Jahan, John Frazee, Neil Martin, Fernando Viñuela
雑誌名: J Neurosurg. 2003 May;98(5):959-66. doi: 10.3171/jns.2003.98.5.0959.
Abstract/Text OBJECT: The authors report on their 11 years' experience with embolization of cerebral aneurysms using Guglielmi Detachable Coil (GDC) technology and on the attendant anatomical and clinical outcomes.
METHODS: Since December 1990, 818 patients harboring 916 aneurysms were treated with GDC embolization at University of California at Los Angeles Medical Center. For comparative purposes, the patients were divided into two groups: Group A included their initial 5 years' experience with 230 patients harboring 251 aneurysms and Group B included the later 6 years' experience with 588 patients harboring 665 aneurysms. Angiographically demonstrated complete occlusion was achieved in 55% of aneurysms and a neck remnant was displayed in 35.4% of lesions. Incomplete embolization was performed in 3.5% of aneurysms, and in 5% occlusion was attempted unsuccessfully. A comparison between the two groups revealed a higher complete embolization rate in patients in Group B compared with that in Group A patients (56.8 and 50.2%, respectively). The overall morbidity/mortality rate was 9.4%. Angiographic follow ups were obtained in 53.4% of cases of aneurysms, and recanalization was exhibited in 26.1% of aneurysms in Group A and 17.2% of those in Group B. The overall recanalization rate was 20.9%. Note that recanalization was related to the size of the dome and neck of the aneurysm. Overall incidence of delayed aneurysm rupture was 1.6%, a rate that improved in the past 5 years to 0.5%. Ten of 12 delayed ruptures occurred in large or giant aneurysms.
CONCLUSIONS: The clinical and postembolization outcomes in patients treated with the GDC system have improved in the past 5 years. Aneurysm recanalization, however, is still a major limitation of current GDC therapy. Follow-up angiography is mandatory after GDC embolization of cerebral aneurysms. Further technical and device improvements are mandatory to overcome current GDC limitations.

PMID 12744354  J Neurosurg. 2003 May;98(5):959-66. doi: 10.3171/jns.20・・・
著者: K Tsutsumi, K Ueki, M Usui, S Kwak, T Kirino
雑誌名: Stroke. 1998 Dec;29(12):2511-3.
Abstract/Text BACKGROUND AND PURPOSE: The neck clipping of cerebral aneurysms is a well-established treatment for subarachnoid hemorrhage (SAH) caused by aneurysmal rupture. However, it is still unclear how great a risk of recurrence patients with a successfully treated aneurysm carry over a long-term period.
METHODS: Of 425 patients with SAH surgically treated in Aizu Chuou Hospital from 1976 to 1994, 220 cases meeting the following criteria were studied: (1) all aneurysms detected by 3- or 4-vessel cerebral angiography were clipped, (2) complete obliteration of aneurysm(s) was confirmed by postoperative angiography, and (3) the patient survived >3 years. All patients were traced until January 1998 for recurrent SAH or death. The mean follow-up period was 9.9 (range, 3 to 21) years.
RESULTS: Six patients (2.7%) had recurrent SAH, each with an interval ranging from 3 to 17 years (mean, 11 years) since the original treatment. In addition, 2 patients were found to have regrowth of the originally operated aneurysms. The cumulative recurrence rate of SAH, calculated using the Kaplan-Meier method, was 2.2% at 10 years and 9. 0% at 20 years after the original treatment.
CONCLUSIONS: The recurrence rate was considerably higher than the previously reported risk of SAH in the normal population, and the rate increased with time. These data indicate that patients with ruptured cerebral aneurysms still carry higher risks for SAH in a long-term period, even after complete obliteration of the aneurysm, and that periodic examination to detect recurrent aneurysms may be indicated for such patients.

PMID 9836760  Stroke. 1998 Dec;29(12):2511-3.
著者: C A David, A G Vishteh, R F Spetzler, M Lemole, M T Lawton, S Partovi
雑誌名: J Neurosurg. 1999 Sep;91(3):396-401. doi: 10.3171/jns.1999.91.3.0396.
Abstract/Text OBJECT: This study was undertaken to evaluate the long-term angiographic outcome of surgically treated aneurysms, which is unknown. Specifically, the incidence of recurrent aneurysms, the fate of residual necks, and the de novo formation of aneurysms were evaluated.
METHODS: One hundred two patients (80 females and 22 males; mean age 49 years; range 12-78 years) harboring a total of 167 aneurysms underwent late follow-up angiography; 160 aneurysms were surgically treated. Late angiographic follow-up review was obtained at a mean of 4.4 +/- 1.6 years postsurgery (range 2.6-9.7 years). Late follow-up angiography revealed two recurrent aneurysms (1.5%) of 135 clipped aneurysms without residua. Of 12 aneurysms with known residua, there were eight "dog-ear" residua, of which two (25%) enlarged. One hemorrhage was noted, yielding a hemorrhage risk of 1.9% per year. A second subgroup with broad-based residua revealed dramatic regrowth in three of four cases. Eight de novo aneurysms were found in six patients, for an annual risk of 1.8% per year. A history of multiple aneurysms was associated with de novo aneurysm formation (p = 0.049, chi-square analysis).
CONCLUSIONS: This study confirms the long-term efficacy of aneurysm clip ligation. In addition, the authors found there is a small but significant risk of de novo aneurysm formation, particularly in patients with multiple aneurysms. Most residual aneurysm rests appear to remain stable, although a subset may enlarge or rupture. These findings support the rationale for late angiographic follow-up review in patients with aneurysms.

PMID 10470813  J Neurosurg. 1999 Sep;91(3):396-401. doi: 10.3171/jns.1・・・

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