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脳動静脈奇形

著者: 新谷祐貴1) 東京大学医学部附属病院 脳神経外科

著者: 斉藤延人2) 東京大学 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:2021/06/30
患者向け説明資料

概要・推奨   

  1. 脳動静脈奇形、もしくは脳動静脈奇形に起因する脳卒中が疑われた場合、頭部CTMRIで頭蓋内精査を行う。
  1. 脳動静脈奇形と診断した場合、血管撮影を行い、重症度評価を行うことが治療方針決定上重要となる。
  1. 脳動静脈奇形と診断した場合、出血予防目的の治療の必要性を検討する。治療適応は、年齢や重症度から予想される出血リスクと治療に伴う合併症リスクを比較し決定する。
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必
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:
新谷祐貴 : 特に申告事項無し[2021年]
斉藤延人 : 特に申告事項無し[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、下記について加筆修正を行った。
  1. 脳卒中治療ガイドライン2015[追補2019]より、未破裂脳動静脈奇形に対する治療方針をupdateした。
  1. 未破裂脳動静脈奇形に対する多施設共同前向きランダム化比較試験(ARUBA study)の最終結果報告(2020年)を追加した。
  1. その他、新たな知見を交えてminor updateした。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 脳動静脈奇形(arteriovenous malformation、AVM)は、脳実質内の拡張した動脈と静脈からなる先天性の異常集塊であり、このナイダスと呼ばれる脆弱な血管塊を介して直接静脈へと還流する脳動静脈シャントが病変の主体である。
 
脳動静脈奇形の代表的なシェーマ

動脈(赤)からナイダスに注いだ血管が拡張した静脈(青)に流入する。

出典

img1:  花北俊哉先生ご提供
 
 
 
  1. この動静脈吻合のため、特に静脈側に過大な圧負荷がかかり静脈は不完全な弾性板を伴って拡張し、出血の原因となる。
  1. AVMは、人口10万人あたり年間1~2人に発生する先天性疾患と考えられており、40歳未満の若年者で最も多く発症する。発症形式としては、約50%がクモ膜下出血や脳内出血などの出血で発症し、20~25%はけいれん発作を契機に、15%程度は慢性頭痛の精査にて発見される。
  1. 非出血発症AVMの場合、年間出血率は1.7~2.2%程度である。初回出血による死亡率は10~30%、重篤な神経学的合併症を伴う確率は10~20%あるとされている。
  1. 出血発症AVMでは、初回出血後に再出血を起こす危険性が、出血後1年間は6~17%と高くなり、その後は再び2~3%/年の出血率に低下する。
  1. 若年者に多く発症する疾患であるため、生命をも左右しかねない出血の予防が治療の主な目的となり、治療適応は、年齢から予想される出血に伴う危険性と治療に伴う合併症の可能性を比較したうえで決定される。
 
  1. 疫学、予後に関するエビデンスOG(参考文献:[1][2][3][4]
  1. 生涯出血率は、近似式で(105-年齢)%で表されるとされる。
  1. 出血発症例の年間出血率は出血後最初の1年で6~17.8%と高く、その後通常の出血率に低下する。
  1. 非出血発症例では、自然歴での出血率は出血発症例よりも有意に低いとされる。
  1. 出血発症例では、出血後最初の1年間は出血率が上昇する。
  1. わが国で行われたYamadaらの報告では、年間出血率は未出血群が3.12%、出血群の年間出血率は6.8%で、最初の1年が15.42%で、その後年々低下し、5年以後は1.72%であった。
  1. grade4,5の自然歴に関しては、年間1.1%と低いとする報告と10.5%と高いとする報告もある。
問診・診察のポイント  
  1. 出血性発症の場合はクモ膜下出血を併発することもあり、頭痛を含めた病歴の聴取が必要である。本人は自覚していないが、視野欠損などを認める場合もあり、一般的な脳神経所見に沿った神経所見診察を行う。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: Juha A Hernesniemi, Reza Dashti, Seppo Juvela, Kristjan Väärt, Mika Niemelä, Aki Laakso
雑誌名: Neurosurgery. 2008 Nov;63(5):823-9; discussion 829-31. doi: 10.1227/01.NEU.0000330401.82582.5E.
Abstract/Text OBJECTIVE: Long-term follow-up studies in patients with brain arteriovenous malformations (AVM) have yielded contradictory results regarding both risk factors for rupture and annual rupture rate. We performed a long-term follow-up study in an unselected, consecutive patient population with AVMs admitted to the Department of Neurosurgery at Helsinki University Central Hospital between 1942 and 2005.
METHODS: Patients with untreated AVMs were followed from admission until death, occurrence of AVM rupture, initiation of treatment, or until the end of 2005. Patients with at least 1 month of follow-up were included in further analysis. Annual and cumulative incidence rates of AVM rupture as well as several potential risk factors for rupture were analyzed using Kaplan-Meier life table analyses and Cox proportional hazards regression models.
RESULTS: We identified 238 patients with a mean follow-up period of 13.5 years (range, 1 month-53.1 years). The average annual risk of hemorrhage from AVMs was 2.4%. The risk was highest during the first 5 years after diagnosis, decreasing thereafter. Risk factors predicting subsequent AVM hemorrhage in univariate analysis were young age, previous rupture, deep and infratentorial locations, and exclusively deep venous drainage. Previous rupture, large AVM size, and infratentorial and deep locations were independent risk factors according to multivariate models.
CONCLUSION: According to this long-term follow-up study, AVMs with previous rupture and large size, as well as with infratentorial and deep locations have the highest risk of subsequent hemorrhage. This risk is highest during the first few years after diagnosis but remains significant for decades.

PMID 19005371  Neurosurgery. 2008 Nov;63(5):823-9; discussion 829-31. ・・・
著者: Shigeki Yamada, Yasushi Takagi, Kazuhiko Nozaki, Ken-ichiro Kikuta, Nobuo Hashimoto
雑誌名: J Neurosurg. 2007 Nov;107(5):965-72. doi: 10.3171/JNS-07/11/0965.
Abstract/Text OBJECT: The aim of this study was to identify the natural history of untreated cerebral arteriovenous malformations (AVMs) and the risk factors for subsequent hemorrhage after an initial AVM diagnosis.
METHODS: The authors studied 305 consecutive patients with AVMs at the Kyoto University Hospital between 1983 and 2005. These patients were followed up until the first subsequent hemorrhage, the start of any treatment, or the end of 2005. Possible risk factors that were investigated included age at initial diagnosis, sex, type of initial presentation, size and location of the AVM nidus, and the venous drainage pattern. Subsequent hemorrhage occurred in 26 patients from the hemorrhagic group during 380 patient-years, and in 16 patients from the nonhemorrhagic group during 512 patient-years.
RESULTS: The annual bleeding rate in the hemorrhagic group was 6.84% after the initial hemorrhage; however, that rate decreased in the first 5 years (15.42% in the first year, 5.32% in the subsequent 4 years, and 1.72% in more than 5 years). In the nonhemorrhagic group (annual bleeding rate of 3.12%), the patients initially presenting with headaches (annual bleeding rate of 6.48%) or asymptomatic presentations (annual bleeding rate of 6.44%) had a higher risk for subsequent hemorrhage. Conversely, those patients presenting with seizures (annual bleeding rate of 2.20%) or neurological deficits (annual bleeding rate of 1.73%) had a lower risk. A significantly increased risk (p < 0.05) of rebleeding was found among children (hazard ratio [HR] = 2.69), females (HR = 2.93), or patients with deep-seated AVMs (HR = 3.07).
CONCLUSIONS: Children, females, and patients with deep-seated AVMs had a threefold increased risk of rebleeding after an initial cerebral AVM. This increased risk was highest in the first year after the initial hemorrhage, and thereafter gradually decreased.

PMID 17977268  J Neurosurg. 2007 Nov;107(5):965-72. doi: 10.3171/JNS-0・・・
著者: Alexander X Halim, S Claiborne Johnston, Vineeta Singh, Charles E McCulloch, John P Bennett, Achal S Achrol, Stephen Sidney, William L Young
雑誌名: Stroke. 2004 Jul;35(7):1697-702. doi: 10.1161/01.STR.0000130988.44824.29. Epub 2004 May 27.
Abstract/Text BACKGROUND AND PURPOSE: Accurate estimates for risk and rates of intracranial hemorrhage (ICH) in the natural course of patients harboring brain arteriovenous malformation (BAVM) are needed to provide a quantitative basis for planning clinical trials to evaluate interventional strategies and to help guide practice management.
METHODS: We identified patients with BAVM at the Kaiser Permanente Northern California health maintenance organization and documented their clinical course. The influences of age at diagnosis, gender, race-ethnicity, ICH at presentation, venous draining pattern, and BAVM size on ICH subsequent to presentation were studied using the multivariate Cox proportional hazards model and Kaplan-Meier curves.
RESULTS: We identified 790 patients with BAVM (51% female; 63% white; mean age+/-SD at diagnosis: 38+/-19 years) between 1961 and 2001. Patients who presented with ICH experienced a higher rate of subsequent ICH than those who presented without ICH under multivariate analysis (hazard ratio, 3.6; 95% CI, 1.1 to 11.9; P<0.032). The effect was similar across race-ethnicity and gender. This difference in ICH rates was greatest in the first year (7% versus 3% per year) and converged over time. The effect of subsequent ICH on functional status was similar to that of the initial ICH.
CONCLUSIONS: Presentation with ICH was the most important predictor of future ICH, confirming previous studies. Future ICH had similar impact on functional outcome as incident ICH. Intervention to prevent ICH would be of potentially greater benefit to patients presenting with ICH, although the advantage decreases over time.

PMID 15166396  Stroke. 2004 Jul;35(7):1697-702. doi: 10.1161/01.STR.00・・・
著者: D Kondziolka, M R McLaughlin, J R Kestle
雑誌名: Neurosurgery. 1995 Nov;37(5):851-5. doi: 10.1227/00006123-199511000-00001.
Abstract/Text We present a simple risk prediction formula for arteriovenous malformation hemorrhage. Natural history studies have shown an annual risk of hemorrhage of 2 to 4% for patients with brain arteriovenous malformations. Although decision analysis programs and biostatistical models are available to predict long-term risks of hemorrhage, we hypothesized that there was varying knowledge regarding the use of such programs within the general neurosurgical community. To obtain information on the current use of risk data, we performed a survey of neurosurgeons at national meetings in 1988 and 1994. Neurosurgeons were asked to define the risk for arteriovenous malformation hemorrhage in the young adult patient over a 20- to 30-year period, given a 3 or 4% annual risk of hemorrhage. A wide range of answers was obtained (1-100% risk), and many different methods of calculation were used. The use of the multiplicative law of probability formula requires only knowledge of patient age and annual hemorrhage risk. Risk of hemorrhage = 1 - (risk of no hemorrhage) expected years of remaining life. The assumptions pertaining to this multiplicative formula include a constant yearly risk of hemorrhage and the independent behavior of all years of observation. We calculated the predictions of risk of hemorrhage across all age groups, as modified by published survival data. We think the use of this formula is justified by published natural history data across different ages and populations and that it is a simple and reasonable alternative to other methods of calculation.

PMID 8559331  Neurosurgery. 1995 Nov;37(5):851-5. doi: 10.1227/000061・・・
著者: R F Spetzler, N A Martin
雑誌名: J Neurosurg. 1986 Oct;65(4):476-83. doi: 10.3171/jns.1986.65.4.0476.
Abstract/Text An important factor in making a recommendation for treatment of a patient with arteriovenous malformation (AVM) is to estimate the risk of surgery for that patient. A simple, broadly applicable grading system that is designed to predict the risk of morbidity and mortality attending the operative treatment of specific AVM's is proposed. The lesion is graded on the basis of size, pattern of venous drainage, and neurological eloquence of adjacent brain. All AVM's fall into one of six grades. Grade I malformations are small, superficial, and located in non-eloquent cortex; Grade V lesions are large, deep, and situated in neurologically critical areas; and Grade VI lesions are essentially inoperable AVM's. Retrospective application of this grading scheme to a series of surgically excised AVM's has demonstrated its correlation with the incidence of postoperative neurological complications. The application of a standardized grading scheme will enable a comparison of results between various clinical series and between different treatment techniques, and will assist in the process of management decision-making.

PMID 3760956  J Neurosurg. 1986 Oct;65(4):476-83. doi: 10.3171/jns.19・・・
著者: Robert F Spetzler, Francisco A Ponce
雑誌名: J Neurosurg. 2011 Mar;114(3):842-9. doi: 10.3171/2010.8.JNS10663. Epub 2010 Oct 8.
Abstract/Text OBJECT: The authors propose a 3-tier classification for cerebral arteriovenous malformations (AVMs). The classification is based on the original 5-tier Spetzler-Martin grading system, and reflects the treatment paradigm for these lesions. The implications of this modification in the literature are explored.
METHODS: Class A combines Grades I and II AVMs, Class B are Grade III AVMs, and Class C combines Grades IV and V AVMs. Recommended management is surgery for Class A AVMs, multimodality treatment for Class B, and observation for Class C, with exceptions to the latter including recurrent hemorrhages and progressive neurological deficits. To evaluate whether combining grades is warranted from the perspective of surgical outcomes, the 3-tier system was applied to 1476 patients from 7 surgical series in which results were stratified according to Spetzler-Martin grades.
RESULTS: Pairwise comparisons of individual Spetzler-Martin grades in the series analyzed showed the fewest significant differences (p < 0.05) in outcomes between Grades I and II AVMs and between Grades IV and V AVMs. In the pooled data analysis, significant differences in outcomes were found between all grades except IV and V (p = 0.38), and the lowest relative risks were found between Grades I and II (1.066) and between Grades IV and V (1.095). Using the pooled data, the predictive accuracies for surgical outcomes of the 5-tier and 3-tier systems were equivalent (receiver operating characteristic curve area 0.711 and 0.713, respectively).
CONCLUSIONS: Combining Grades I and II AVMs and combining Grades IV and V AVMs is justified in part because the differences in surgical results between these respective pairs are small. The proposed 3-tier classification of AVMs offers simplification of the Spetzler-Martin system, provides a guide to treatment, and is predictive of outcome. The revised classification not only simplifies treatment recommendations; by placing patients into 3 as opposed to 5 groups, statistical power is markedly increased for series comparisons.

PMID 20932095  J Neurosurg. 2011 Mar;114(3):842-9. doi: 10.3171/2010.8・・・
著者: Michael T Lawton, UCSF Brain Arteriovenous Malformation Study Project
雑誌名: Neurosurgery. 2003 Apr;52(4):740-8; discussion 748-9.
Abstract/Text OBJECTIVE: To analyze surgical results for the highly variable Spetzler-Martin Grade III arteriovenous malformations (AVMs), to demonstrate that outcomes vary among the different types of Grade III lesions, and to introduce a simple modification of the grading scale that might improve its usefulness for these AVMs.
METHODS: In a consecutive series of 174 brain AVMs resected from 174 patients during a period of 4.8 years, 76 AVMs (45.2%) were Grade III. There were 35 small AVMs (S1V1E1) (46.1%), 14 medium/deep AVMs (S2V1E0) (18.4%), and 27 medium/eloquent AVMs (S2V0E1) (35.5%). No large Grade III AVM (S3V0E0) was treated.
RESULTS: Complete AVM resection was accomplished for 74 patients (surgical obliteration rate, 97.4%). Three patients (3.9%) experienced permanent, treatment-associated, neurological morbidity, and three patients died (surgical mortality rate, 3.9%). Good outcomes (Rankin scale scores of CONCLUSION: Grade III AVMs are a heterogeneous group, with each type possessing different surgical risks, and the Spetzler-Martin grading scale should be modified accordingly. Grade III- AVMs (S1V1E1) have a surgical risk similar to that of low-grade AVMs and can be safely treated with microsurgical resection. Grade III+ AVMs (S2V0E1) have a surgical risk similar to that of high-grade AVMs and are best managed conservatively. Grade III AVMs (S2V1E0) have intermediate surgical risks and require judicious selection for surgery. Grade III* AVMs (S3V0E0) are either exceedingly rare, with a surgical risk that is unclear, or theoretical lesions with no clinical relevance.

PMID 12657169  Neurosurgery. 2003 Apr;52(4):740-8; discussion 748-9.
著者: Mahesh V Jayaraman, Mary L Marcellus, Huy M Do, Steven D Chang, Jarrett K Rosenberg, Gary K Steinberg, Michael P Marks
雑誌名: Stroke. 2007 Feb;38(2):325-9. doi: 10.1161/01.STR.0000254497.24545.de. Epub 2006 Dec 28.
Abstract/Text BACKGROUND AND PURPOSE: We sought to examine the prospective annual risk of hemorrhage in patients harboring Spetzler-Martin grades IV and V arteriovenous malformations (AVMs) before and after initiation of treatment.
METHODS: Medical records of 61 consecutive patients presenting with Spetzler-Martin grades IV and V AVMs were retrospectively reviewed for demographics, angiographic features, presenting symptom(s), and time of all hemorrhage events, before or after treatment initiation. Pretreatment hemorrhage rates (excluding hemorrhages at presentation) and posttreatment rates were subsequently calculated. Modified Rankin Scale (mRS) scores before and after treatment were recorded.
RESULTS: The annual pretreatment hemorrhage rate for all patients was 10.4% per year (95% CI, 2.2 to 15.4%), 13.9% (95% CI, 3.5 to 22.1%) in patients with hemorrhagic presentation and 7.3% (2.6 to 14.3%) in patients with nonhemorrhagic presentation. Posttreatment hemorrhage rates were 6.1% per year (95% CI, 2.5 to 13.2%) for all patients, 5.6% (95% CI, 2.1 to 11.8%) for patients presenting with hemorrhage and 6.4% (95% CI, 1.6 to 10.1%) in patients with nonhemorrhagic presentation. A noninferiority test showed that the posttreatment hemorrhage rate was less than or equal to the pretreatment hemorrhage rate (P<0.0001), with some indication that the reduction was greatest in patients with hemorrhagic presentation. Of the 62 patients, 51 (82%) had an mRS score of 0 to 2 before treatment, and 47 (76%) had an mRS score of 0 to 2 at the last follow-up after treatment.
CONCLUSIONS: The annual rate of hemorrhage in grades IV and V AVMs is higher in this series than reported for all AVMs, which may reflect some referral bias in this single-center study. Nevertheless, initiation of treatment does not appear to increase the rate of subsequent hemorrhage. Treatment for these lesions may be warranted, given their poor natural history.

PMID 17194881  Stroke. 2007 Feb;38(2):325-9. doi: 10.1161/01.STR.00002・・・
著者: Patrick P Han, Francisco A Ponce, Robert F Spetzler
雑誌名: J Neurosurg. 2003 Jan;98(1):3-7. doi: 10.3171/jns.2003.98.1.0003.
Abstract/Text OBJECT: In this study the authors quantified a subgroup of patients with Spetzler-Martin Grades IV and V arteriovenous malformations (AVMs) recommended for complete, partial, or no treatment, and calculated the retrospective hemorrhage rate for these lesions.
METHODS: Between July 1997 and May 2000, 73 consecutive patients with Grades IV and V AVMs were evaluated prospectively by the cerebrovascular team at Barrow Neurological Institute. Treatment recommendations given to the patients or referring physicians were classified as complete treatment, partial treatment, and no treatment. Retrospectively, the hemorrhage rates associated with these treatment groups were also calculated. In the prospective portion of the study (the intention-to-treat analysis), no treatment of the AVM, was recommended for 55 patients (75%) and partial treatment was recommended for seven patients (10%). Aneurysms associated with an AVM were obliterated by surgical or endovascular treatment in seven patients (10%), and complete surgical removal was recommended for four patients (5%). The overall hemorrhage rate for Grades IV and V AVMs was 1.5% per year. The annual risk of hemorrhage was 10.4% among patients who previously had received incomplete treatment, compared with patients without previous treatment.
CONCLUSIONS: The hemorrhage risk of 1.5% per year, which was associated with Grades IV and V AVMs appears to be lower than that reported for Grades I through III AVMs. The authors recommend that no treatment be given for most Grades IV and V AVMs. No evidence indicates that partial treatment of an AVM reduces a patient's risk of hemorrhage. In fact, partial treatment may worsen the natural history of an AVM. The authors do not support palliative treatment of AVMs, except in the specific circumstances of arterial or intranidal aneurysms or progressive neurological deficits related to vascular steal. Complete treatment is warranted for patients with progressive neurological deficits caused by hemorrhage of the AVM. This selection process plays a significant role in the relatively low combined morbidity and mortality rates for Grade IV and Grade V AVMs (17 and 22%, respectively) reported by the cerebrovascular group in both retrospective and prospective studies.

PMID 12546345  J Neurosurg. 2003 Jan;98(1):3-7. doi: 10.3171/jns.2003.・・・
著者: Aki Laakso, Reza Dashti, Seppo Juvela, Puchong Isarakul, Mika Niemelä, Juha Hernesniemi
雑誌名: Neurosurgery. 2011 Feb;68(2):372-7; discussion 378. doi: 10.1227/NEU.0b013e3181ffe931.
Abstract/Text BACKGROUND: Treatment of Spetzler-Martin Grade IV and V brain arteriovenous malformations (ie, high-grade AVMs) carries a high risk of morbidity and even mortality. However, little is known about the behavior of these lesions if left untreated.
OBJECTIVE: To investigate the natural history of patients with high-grade AVMs.
METHODS: Patients with untreated high-grade AVMs admitted to our center between 1952 and 2005 were followed from admission until death, AVM rupture, or initiation of treatment. Rates of rupture and various risk factors were analyzed using Kaplan-Meier life table analyses and Cox proportional hazards models. Functional outcome was assessed 1 year after possible AVM rupture using the Glasgow Outcome Scale.
RESULTS: Sixty-three patients with a mean follow-up time of 11.0 years (range, 1 month to 39.6 years) were identified. Twenty-three patients (37%) experienced a subsequent rupture. The average annual rate of rupture was 3.3%. In patients with hemorrhagic presentation, the annual rate was 6.0%, compared to 1.1% in patients with unruptured AVMs (P = .001, log-rank test; hazard ratio, 5.09 [1.40-18.5, 95% CI]; P = .013, multivariate Cox regression model). One year after the first subsequent rupture, 6 patients (26%) had died, and 9 (39%) had moderate or severe disability.
CONCLUSION: Untreated high grade AVMs presenting with hemorrhage have a significant risk of subsequent rupture, and their rupture carries a higher risk of case fatality and permanent morbidity than AVMs in general. The risks associated with their treatment should be appraised in light of perilous natural history.

PMID 21135742  Neurosurgery. 2011 Feb;68(2):372-7; discussion 378. doi・・・
著者: C S Ogilvy, P E Stieg, I Awad, R D Brown, D Kondziolka, R Rosenwasser, W L Young, G Hademenos, Special Writing Group of the Stroke Council, American Stroke Association
雑誌名: Stroke. 2001 Jun;32(6):1458-71.
Abstract/Text
PMID 11387517  Stroke. 2001 Jun;32(6):1458-71.
著者: Christian Stapf
雑誌名: Acta Neurochir Suppl. 2010;107:83-5. doi: 10.1007/978-3-211-99373-6_13.
Abstract/Text A Randomized Trial of Unruptured Brain AVMs is a multidisciplinary international randomized controlled clinical trial including 800 adult patients with the diagnosis of an unruptured brain AVM. Patients willing to participate are randomly assigned to either best possible invasive therapy (endovascular, neurosurgical, and/or radiation therapy) or medical management without intervention. The study protocol does not modify any routine treatment strategies in either arm. Patients will be followed for a minimum of 5 years and a maximum of 10 years from randomization.The primary outcome measure is the composite endpoint of death from any cause or stroke (clinically symptomatic hemorrhage or infarction confirmed by imaging). The secondary outcome measure is long-term clinical status by Rankin Scale, NIHSS, SF-36, and EuroQol.Patient enrollment was successfully started in 2007. Participating sites currently include multidisciplinary treatment centers in North and South America, Australasia, and Europe (including Australia, Austria, Brazil, Canada, Finland, France, Germany, Italy, Netherlands, Spain, South Korea, Switzerland, UK, and the USA).The trial is sponsored and monitored by the US NIH/NINDS (NCT00389181).

PMID 19953376  Acta Neurochir Suppl. 2010;107:83-5. doi: 10.1007/978-3・・・
著者: J P Mohr, Michael K Parides, Christian Stapf, Ellen Moquete, Claudia S Moy, Jessica R Overbey, Rustam Al-Shahi Salman, Eric Vicaut, William L Young, Emmanuel Houdart, Charlotte Cordonnier, Marco A Stefani, Andreas Hartmann, Rüdiger von Kummer, Alessandra Biondi, Joachim Berkefeld, Catharina J M Klijn, Kirsty Harkness, Richard Libman, Xavier Barreau, Alan J Moskowitz, international ARUBA investigators
雑誌名: Lancet. 2014 Feb 15;383(9917):614-21. doi: 10.1016/S0140-6736(13)62302-8. Epub 2013 Nov 20.
Abstract/Text BACKGROUND: The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations (ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy.
METHODS: Adult patients (≥18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1:1 ratio, with random permuted block design [block size 2, 4, or 6], stratified by clinical site) to medical management with interventional therapy (ie, neurosurgery, embolisation, or stereotactic radiotherapy, alone or in combination) or medical management alone (ie, pharmacological therapy for neurological symptoms as needed). Patients, clinicians, and investigators are aware of treatment assignment. The primary outcome is time to the composite endpoint of death or symptomatic stroke; the primary analysis is by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389181.
FINDINGS: Randomisation was started on April 4, 2007, and was stopped on April 15, 2013, when a data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health recommended halting randomisation because of superiority of the medical management group (log-rank Z statistic of 4·10, exceeding the prespecified stopping boundary value of 2·87). At this point, outcome data were available for 223 patients (mean follow-up 33·3 months [SD 19·7]), 114 assigned to interventional therapy and 109 to medical management. The primary endpoint had been reached by 11 (10·1%) patients in the medical management group compared with 35 (30·7%) in the interventional therapy group. The risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group (hazard ratio 0·27, 95% CI 0·14-0·54). No harms were identified, other than a higher number of strokes (45 vs 12, p<0·0001) and neurological deficits unrelated to stroke (14 vs 1, p=0·0008) in patients allocated to interventional therapy compared with medical management.
INTERPRETATION: The ARUBA trial showed that medical management alone is superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain arteriovenous malformations followed up for 33 months. The trial is continuing its observational phase to establish whether the disparities will persist over an additional 5 years of follow-up.
FUNDING: National Institutes of Health, National Institute of Neurological Disorders and Stroke.

Copyright © 2014 Elsevier Ltd. All rights reserved.
PMID 24268105  Lancet. 2014 Feb 15;383(9917):614-21. doi: 10.1016/S014・・・
著者: Jay P Mohr, Jessica R Overbey, Andreas Hartmann, Rüdiger von Kummer, Rustam Al-Shahi Salman, Helen Kim, H Bart van der Worp, Michael K Parides, Marco A Stefani, Emmanuel Houdart, Richard Libman, John Pile-Spellman, Kirsty Harkness, Charlotte Cordonnier, Ellen Moquete, Alessandra Biondi, Catharina J M Klijn, Christian Stapf, Alan J Moskowitz, ARUBA co-investigators
雑誌名: Lancet Neurol. 2020 Jul;19(7):573-581. doi: 10.1016/S1474-4422(20)30181-2.
Abstract/Text BACKGROUND: In A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA), randomisation was halted at a mean follow-up of 33·3 months after a prespecified interim analysis showed that medical management alone was superior to the combination of medical management and interventional therapy in preventing symptomatic stroke or death. We aimed to study whether these differences persisted through 5-years' follow-up.
METHODS: ARUBA was a non-blinded, randomised trial done at 39 clinical centres in nine countries. Adults (age ≥18 years) diagnosed with an unruptured brain arteriovenous malformation, who had never undergone interventional therapy, and were considered by participating clinical centres to be suitable for intervention to eradicate the lesion, were eligible for inclusion. Patients were randomly assigned (1:1) by a web-based data collection system, stratified by clinical centre in a random permuted block design with block sizes of two, four, and six, to medical management alone or with interventional therapy (neurosurgery, embolisation, or stereotactic radiotherapy, alone or in any combination, sequence, or number). Although patients and investigators at a given centre were not masked to treatment assignment, investigators at other centres and those in the clinical coordinating centre were not informed of assignment or outcomes at any of the centres. The primary outcome was time to death or symptomatic stroke confirmed by imaging, assessed by a neurologist at each centre not involved in the management of participants' care, and monitored by an independent committee using an adaptive approach with interim analyses. Enrolment began on April 4, 2007, and was halted on April 15, 2013, after which follow-up continued until July 15, 2015. All analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00389181.
FINDINGS: Of 1740 patients screened, 226 were randomly assigned to medical management alone (n=110) or medical management plus interventional therapy (n=116). During a mean follow-up of 50·4 months (SD 22·9), the incidence of death or symptomatic stroke was lower with medical management alone (15 of 110, 3·39 per 100 patient-years) than with medical management with interventional therapy (41 of 116, 12·32 per 100 patient-years; hazard ratio 0·31, 95% CI 0·17 to 0·56). Two patients in the medical management group and four in the interventional therapy group (two attributed to intervention) died during follow-up. Adverse events were observed less often in patients allocated to medical management compared with interventional therapy (283 vs 369; 58·97 vs 78·73 per 100 patient-years; risk difference -19·76, 95% CI -30·33 to -9·19).
INTERPRETATION: After extended follow-up, ARUBA showed that medical management alone remained superior to interventional therapy for the prevention of death or symptomatic stroke in patients with an unruptured brain arteriovenous malformation. The data concerning the disparity in outcomes should affect standard specialist practice and the information presented to patients. The even longer-term risks and differences between the two therapeutic approaches remains uncertain.
FUNDING: National Institute of Neurological Disorders and Stroke for the randomisation phase and Vital Projects Fund for the follow-up phase.

Copyright © 2020 Elsevier Ltd. All rights reserved.
PMID 32562682  Lancet Neurol. 2020 Jul;19(7):573-581. doi: 10.1016/S14・・・
著者: Dale Ding, Robert M Starke, Hideyuki Kano, David Mathieu, Paul Huang, Douglas Kondziolka, Caleb Feliciano, Rafael Rodriguez-Mercado, Luis Almodovar, Inga S Grills, Danilo Silva, Mahmoud Abbassy, Symeon Missios, Gene H Barnett, L Dade Lunsford, Jason P Sheehan
雑誌名: Stroke. 2016 Feb;47(2):342-9. doi: 10.1161/STROKEAHA.115.011400. Epub 2015 Dec 10.
Abstract/Text BACKGROUND AND PURPOSE: The benefit of intervention for patients with unruptured cerebral arteriovenous malformations (AVMs) was challenged by results demonstrating superior clinical outcomes with conservative management from A Randomized Trial of Unruptured Brain AVMs (ARUBA). The aim of this multicenter, retrospective cohort study is to analyze the outcomes of stereotactic radiosurgery for ARUBA-eligible patients.
METHODS: We combined AVM radiosurgery outcome data from 7 institutions participating in the International Gamma Knife Research Foundation. Patients with ≥12 months of follow-up were screened for ARUBA eligibility criteria. Favorable outcome was defined as AVM obliteration, no postradiosurgery hemorrhage, and no permanently symptomatic radiation-induced changes. Adverse neurological outcome was defined as any new or worsening neurological symptoms or death.
RESULTS: The ARUBA-eligible cohort comprised 509 patients (mean age, 40 years). The Spetzler-Martin grade was I to II in 46% and III to IV in 54%. The mean radiosurgical margin dose was 22 Gy and follow-up was 86 months. AVM obliteration was achieved in 75%. The postradiosurgery hemorrhage rate during the latency period was 0.9% per year. Symptomatic and permanent radiation-induced changes occurred in 11% and 3%, respectively. The rates of favorable outcome, adverse neurological outcome, permanent neurological morbidity, and mortality were 70%, 13%, 5%, and 4%, respectively.
CONCLUSIONS: Radiosurgery may provide durable clinical benefit in some ARUBA-eligible patients. On the basis of the natural history of untreated, unruptured AVMs in the medical arm of ARUBA, we estimate that a follow-up duration of 15 to 20 years is necessary to realize a potential benefit of radiosurgical intervention for conservative management in unruptured patients with AVM.

© 2015 American Heart Association, Inc.
PMID 26658441  Stroke. 2016 Feb;47(2):342-9. doi: 10.1161/STROKEAHA.11・・・
著者: W Caleb Rutledge, Adib A Abla, Jeffrey Nelson, Van V Halbach, Helen Kim, Michael T Lawton
雑誌名: Neurosurg Focus. 2014 Sep;37(3):E8. doi: 10.3171/2014.7.FOCUS14242.
Abstract/Text OBJECT: Management of unruptured arteriovenous malformations (AVMs) is controversial. In the first randomized trial of unruptured AVMs (A Randomized Trial of Unruptured Brain Arteriovenous Malformations [ARUBA]), medically managed patients had a significantly lower risk of death or stroke and had better outcomes. The University of California, San Francisco (UCSF) was one of the participating ARUBA sites. While 473 patients were screened for eligibility, only 4 patients were enrolled in ARUBA. The purpose of this study is to report the treatment and outcomes of all ARUBA-eligible patients at UCSF.
METHODS: The authors compared the treatment and outcomes of ARUBA-eligible patients using prospectively collected data from the UCSF brain AVM registry. Similar to ARUBA, they compared the rate of stroke or death in observed and treated patients and used the modified Rankin Scale to grade outcomes.
RESULTS: Of 74 patients, 61 received an intervention and 13 were observed. Most treated patients had resection with or without preoperative embolization (43 [70.5%] of 61 patients). One of the 13 observed patients died after AVM hemorrhage. Nine of the 61 treated patients had a stroke or died. There was no significant difference in the rate of stroke or death (HR 1.34, 95% CI 0.12-14.53, p = 0.81) or clinical impairment (Fisher's exact test, p > 0.99) between observed and treated patients.
CONCLUSIONS: The risk of stroke or death and degree of clinical impairment among treated patients was lower than reported in ARUBA. The authors found no significant difference in outcomes between observed and treated ARUBA-eligible patients at UCSF. Results in ARUBA-eligible patients managed outside that trial led to an entirely different conclusion about AVM intervention, due to the primary role of surgery, judicious surgical selection with established outcome predictors, and technical expertise developed at high-volume AVM centers.

PMID 25175446  Neurosurg Focus. 2014 Sep;37(3):E8. doi: 10.3171/2014.7・・・
著者: Shunya Hanakita, Masahiro Shin, Tomoyuki Koga, Hiroshi Igaki, Nobuhito Saito
雑誌名: Stroke. 2016 May;47(5):1247-52. doi: 10.1161/STROKEAHA.116.013132. Epub 2016 Apr 12.
Abstract/Text BACKGROUND AND PURPOSE: A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) indicated the superiority of medical management in reducing the risks for strokes and other neurological deficits over observation alone. The aim of our study was to verify the rationale for stereotactic radiosurgery (SRS) for small unruptured arteriovenous malformation.
METHODS: A retrospective review was performed for 292 patients with unruptured arteriovenous malformations referred for SRS. The risks for cerebral hemorrhages were statistically compared before and after SRS.
RESULTS: Of the 292 patients in whom arteriovenous malformation was found unruptured at initial diagnosis, 17 sustained hemorrhages in the period between the diagnosis and the initial therapeutic intervention (annual bleeding rate, 2.1%; 95% confidence interval [CI], 1.2%-3.4%). Of the remaining 275 patients, 240 were initially treated with SRS, and 16 sustained a hemorrhage after SRS (annual bleeding rate, 1.1%; 95% CI, 0.6%-1.8%), but only 2 sustained a hemorrhage after angiographic obliteration (annual bleeding rate, 0.3%; 95% CI, 0.04%-1.2%). Comparing the risk of hemorrhage between the periods before and after SRS, a 53% risk reduction was achieved after SRS (hazard ratio, 0.47; 95% CI, 0.24-0.94; P=0.03), and 85% reduction was achieved after angiographic obliteration (hazard ratio, 0.15; 95% CI, 0.02-0.53; P=0.002).
CONCLUSIONS: SRS can significantly reduce the risk of stroke in the patients with small unruptured arteriovenous malformations. To definitively determine the clinical benefits of SRS, a longer follow-up will be necessary. However, based on our results, we can recommend SRS for patients who face a latent risk for stroke from this intractable vascular disease.

© 2016 American Heart Association, Inc.
PMID 27073242  Stroke. 2016 May;47(5):1247-52. doi: 10.1161/STROKEAHA.・・・
著者: A Hartmann, J Pile-Spellman, C Stapf, R R Sciacca, A Faulstich, J P Mohr, H C Schumacher, H Mast
雑誌名: Stroke. 2002 Jul;33(7):1816-20.
Abstract/Text BACKGROUND AND PURPOSE: Independently assessed data on frequency, severity, and determinants of neurological deficits after endovascular treatment of brain arteriovenous malformations (AVMs) are scarce.
METHODS: From the prospective Columbia AVM Study Project, 233 consecutive patients with brain AVM receiving > or =1 endovascular treatments were analyzed. Neurological impairment was assessed by a neurologist using the Rankin Scale before and after completed endovascular therapy. Multivariate logistic regression models were used to identify demographic, clinical, and morphological predictors of treatment-related neurological deficits. The analysis included the components used in the Spetzler-Martin risk score for AVM surgery (AVM size, venous drainage pattern, and eloquence of AVM location).
RESULTS: The 233 patients were treated with 545 endovascular procedures. Mean follow-up time was 9.6 months (SD, 18.1 months). Two hundred patients (86%) experienced no change in neurological status after treatment, and 33 patients (14%) showed treatment-related neurological deficits. Of the latter, 5 (2%) had persistent disabling deficits (Rankin score >2), and 2 (1%) died. Increasing patient age [odds ratio (OR), 1.04; 95% confidence interval (CI), 1.01 to 1.08], number of embolizations (OR, 1.41; 95% CI, 1.16 to 1.70), and absence of a pretreatment neurological deficit (OR, 4.55; 95% CI, 1.03 to 20.0) were associated with new neurological deficits. None of the morphological AVM characteristics tested predicted treatment complications.
CONCLUSIONS: From independent neurological assessment and prospective data collection, our findings suggest a low rate of disabling treatment complications in this center for endovascular brain AVM treatment. Risk predictors for endovascular treatment differ from those for AVM surgery.

PMID 12105359  Stroke. 2002 Jul;33(7):1816-20.
著者: Carlos J Ledezma, Brian L Hoh, Bob S Carter, Johnny C Pryor, Christopher M Putman, Christopher S Ogilvy
雑誌名: Neurosurgery. 2006 Apr;58(4):602-11; discussion 602-11. doi: 10.1227/01.NEU.0000204103.91793.77.
Abstract/Text OBJECTIVE: Embolization is an important therapeutic modality in the multidisciplinary management of arteriovenous malformations (AVM); however, prior series have reported a wide variability in overall complication rates caused by embolization (10-50% neurological deficit, 1-4% mortality). In this study, we reviewed our experience with AVM embolization and analyzed factors that might predict complications and clinical outcomes after AVM embolization.
METHODS: We analyzed our combined neurovascular unit's results with AVM embolization from 1993 to 2004 for the following outcomes measures: 1) clinically significant complications, 2) technical complications without clinical sequelae, 3) discharge Glasgow Outcome Scale score, and 4) death. To determine embolization efficacy, we analyzed perioperative blood transfusion and rate of AVM obliteration. Univariate and multivariate analyses were performed for patient age, sex, history of rupture, history of seizure, associated aneurysms, AVM size, deep venous drainage, eloquent location, Spetzler-Martin grade, number of embolization stages, number of pedicles embolized, and primary treatment modality.
RESULTS: Over an 11 year period, 295 embolization procedures (761 pedicles embolized) were performed in 168 patients with embolization as the primary treatment modality (n = 16) or as an adjunct to surgery (n = 124) or radiosurgery (n = 28). There were a total of 27 complications in this series, of which 11 were clinically significant (6.5% of patients, 3.7% per procedure), and 16 were technical complications (9.5% of patients, 5.4% per procedure). Excellent or good outcomes (Glasgow Outcome Scale > or = 4) were observed in 152 (90.5%) patients. Unfavorable outcomes (Glasgow Outcome Scale 1-3) as a direct result of embolization were both 3.0% at discharge and at follow-up, with a 1.2% embolization-related mortality. In the 124 surgical patients, 96.8% had complete AVM obliteration after initial resection, and 31% received perioperative transfusion (mean 1.4 units packed red blood cells per surgical patient). Predictors of unfavorable outcome caused by embolization by univariate analysis were deep venous drainage (P < 0.05), Spetzler-Martin Grade III to V (P < 0.05), and periprocedural hemorrhage (P < 0.0001) and by multivariate analysis were Spetzler-Martin III to V (odds ratio 10.6, P = 0.03) and periprocedural hemorrhage (odds ratio 17, P = 0.004).
CONCLUSION: In a single-center, retrospective, nonrandomized study, 90.5% of patients had excellent or good outcomes after AVM embolization, with a complication rate lower than previously reported. Spetzler-Martin grade III to V and periprocedural hemorrhage were the most important predictive factors in determining outcome after embolization.

PMID 16575323  Neurosurgery. 2006 Apr;58(4):602-11; discussion 602-11.・・・
著者: Charles S Haw, Karel terBrugge, Robert Willinsky, George Tomlinson
雑誌名: J Neurosurg. 2006 Feb;104(2):226-32. doi: 10.3171/jns.2006.104.2.226.
Abstract/Text OBJECT: The goal of this study was to determine the rates of mortality and morbidity associated with the embolization of arteriovenous malformations (AVMs) of the brain and to analyze the factors related to embolization-related complications.
METHODS: The University of Toronto Brain Vascular Malformation Study Group database was reviewed. Three hundred six patients underwent 513 embolization sessions between November 1984 and September 2002. The combined rate of death and any permanent disabling neurological deficit was 3.9% per patient. Location of the AVM in an eloquent part of the brain, presence of a fistula, and a venous deposition of glue were related to complications. A clinically important reduction in the rate of death and disabling morbidity occurred in the second half of the study period.
CONCLUSIONS: Embolization of AVMs in the brain is associated with low overall rates of mortality and disabling morbidity.

PMID 16509496  J Neurosurg. 2006 Feb;104(2):226-32. doi: 10.3171/jns.2・・・
著者: Isil Saatci, Serdar Geyik, Kivilcim Yavuz, H Saruhan Cekirge
雑誌名: J Neurosurg. 2011 Jul;115(1):78-88. doi: 10.3171/2011.2.JNS09830. Epub 2011 Apr 8.
Abstract/Text OBJECT: The purpose of this study was to present the authors' clinical experience and long-term angiographic and clinical follow-up results in 350 patients with brain arteriovenous malformations (AVMs) treated using prolonged intranidal Onyx injection with a very slow "staged" reflux technique described by the authors.
METHODS: Three hundred and fifty consecutive patients with brain AVMs treated using Onyx between 1999 and 2008 and in whom definitive status for endovascular treatment was reached are presented. There were 206 (59%) male and 144 (41%) female patients, with a mean age of 34 years. There were 607 endovascular sessions performed. Onyx was the only agent used for intranidal injections in all patients, but in 42 patients high-concentration N-butyl cyanoacrylate glue was used adjunctively to close high-flow direct arteriovenous intra- or perinidal fistulas, or when a feeding vessel or nidus perforation and/or dissection occurred.
RESULTS: Angiographically confirmed obliteration was achieved in 179 patients (51%) with only endovascular treatment; 1 patient died due to intracranial hemorrhage after the treatment. Twenty-two patients underwent resection, and 136 patients were sent to radiosurgery after endovascular treatment. In 4 patients embolization therapy was discontinued, and 5 additional patients refused the suggested complementary surgery. In all 178 surviving patients who had angiographically confirmed AVM obliteration by embolization alone, 1-8 years of control angiography (mean 47 months) confirmed stable obliteration, except for 2 patients in whom a very small recruitment was noted in the 1st year on control angiography studies, despite initial apparent total obliteration (recanalization rate 1.1%). In the entire series, 5 patients died; the mortality rate was 1.4%. The permanent morbidity rate was 7.1%.
CONCLUSIONS: With the prolonged intranidal injection technique described herein, Onyx allows the practitioner to achieve higher rates of anatomical cures compared with the cure rates obtained previously with other embolic agents. More importantly, due to this technique's much more effective intranidal penetration, it allows high-grade AVMs to be made radiosurgically treatable in a group of patients for whom there has been no treatment alternative.

PMID 21476804  J Neurosurg. 2011 Jul;115(1):78-88. doi: 10.3171/2011.2・・・
著者: Masahiro Shin, Keisuke Maruyama, Hiroki Kurita, Shunsuke Kawamoto, Masao Tago, Atsuro Terahara, Akio Morita, Keisuke Ueki, Kintomo Takakura, Takaaki Kirino
雑誌名: J Neurosurg. 2004 Jul;101(1):18-24. doi: 10.3171/jns.2004.101.1.0018.
Abstract/Text OBJECT: A large number of clinical studies have been made on treatment outcomes of radiosurgery for arteriovenous malformations (AVMs), but the reported obliteration rates following this treatment vary significantly, perhaps reflecting the different methods and timings of the imaging studies used.
METHODS: The authors retrospectively analyzed their experience with gamma knife surgery in 400 patients with AVMs (follow-up period 1-135 months, median 65 months), with special reference to the imaging modality used in each case. The calculated obliteration rates varied from 68.2 to 92%, depending on imaging modality and timing of evaluation. When only unquestionable imaging data such as demonstrations of a residual nidus on computerized tomography (CT) or magnetic resonance (MR) images or findings on angiograms were used in the calculation, the obliteration rates were 72% at 3 years and 87.3% at 5 years. Factors leading to a better obliteration rate were previous hemorrhage (p = 0.0084), smaller nidus (p = 0.0023), and higher radiation dose to the lesion's margin (p = 0.0495), as determined in a multivariate analysis. Factors leading to an earlier obliteration of the nidus were male sex (p = 0.0001), previous hemorrhage (p = 0.0039), smaller nidus diameter (p = 0.0006), and dose planning using angiography alone (p = 0.0201).
CONCLUSIONS: After the introduction of CT and MR images into dose planning, the conformity and selectivity of dosimetry improved remarkably, although the latency intervals until obliteration were prolonged. Imaging outcomes for AVMs should be evaluated using data provided by longer follow-up periods. The timing of additional treatments for residual AVMs should be decided cautiously, considering the size of the AVM, the patient age and sex, and the history of hemorrhage before radiosurgery.

PMID 15255246  J Neurosurg. 2004 Jul;101(1):18-24. doi: 10.3171/jns.20・・・
著者: Keisuke Maruyama, Nobutaka Kawahara, Masahiro Shin, Masao Tago, Junji Kishimoto, Hiroki Kurita, Shunsuke Kawamoto, Akio Morita, Takaaki Kirino
雑誌名: N Engl J Med. 2005 Jan 13;352(2):146-53. doi: 10.1056/NEJMoa040907.
Abstract/Text BACKGROUND: Angiography shows that stereotactic radiosurgery obliterates most cerebral arteriovenous malformations after a latency period of a few years. However, the effect of this procedure on the risk of hemorrhage is poorly understood.
METHODS: We performed a retrospective observational study of 500 patients with malformations who were treated with radiosurgery with use of a gamma knife. The rates of hemorrhage were assessed during three periods: before radiosurgery, between radiosurgery and the angiographic documentation of obliteration of the malformation (latency period), and after angiographic obliteration.
RESULTS: Forty-two hemorrhages were documented before radiosurgery (median follow-up, 0.4 year), 23 during the latency period (median follow-up, 2.0 years), and 6 after obliteration (median follow-up, 5.4 years). As compared with the period between diagnosis and radiosurgery, the risk of hemorrhage decreased by 54 percent during the latency period (hazard ratio, 0.46; 95 percent confidence interval, 0.26 to 0.80; P=0.006) and by 88 percent after obliteration (hazard ratio, 0.12; 95 percent confidence interval, 0.05 to 0.29; P<0.001). The risk was significantly reduced during the period after obliteration, as compared with the latency period (hazard ratio, 0.26; 95 percent confidence interval, 0.10 to 0.68; P=0.006). The reduction was greater among patients who presented with hemorrhage than among those without hemorrhage at presentation and similar in analyses that took into account the delay in confirming obliteration by means of angiography and analyses that excluded data obtained during the first year after diagnosis.
CONCLUSIONS: Radiosurgery significantly decreases the risk of hemorrhage in patients with cerebral arteriovenous malformations, even before there is angiographic evidence of obliteration. The risk of hemorrhage is further reduced, although not eliminated, after obliteration.

Copyright 2005 Massachusetts Medical Society.
PMID 15647577  N Engl J Med. 2005 Jan 13;352(2):146-53. doi: 10.1056/N・・・
著者: Tomoyuki Koga, Masahiro Shin, Atsuro Terahara, Nobuhito Saito
雑誌名: Neurosurgery. 2011 Jul;69(1):45-51; discussion 51-2. doi: 10.1227/NEU.0b013e31821421d1.
Abstract/Text BACKGROUND: Arteriovenous malformations (AVMs) in the brainstem yield a high risk of hemorrhage. Although stereotactic radiosurgery (SRS) is accepted, because of high surgical morbidity and mortality, outcomes are still unclear.
OBJECTIVE: We previously reported the early results of SRS for brainstem AVMs. Here, we obtained data from a longer follow-up for a larger number of patients and present precise outcomes based on the latest follow-up data.
METHODS: Forty-four patients with brainstem AVMs were treated by SRS. Outcomes such as the rates of obliteration, hemorrhage after treatment, and adverse effects were retrospectively analyzed.
RESULTS: The annual hemorrhage rate before SRS was 17.5%. The mean follow-up period after SRS was 71 months (range, 2-168 months). The actuarial obliteration rate confirmed by angiography was 52% at 5 years. Factors associated with higher obliteration rate were previous hemorrhage (P = .048) and higher margin dose (P = .048). For patients treated with a margin dose of ≥ 18 Gy, the obliteration rate was 71% at 5 years. Persistent worsening of neurological symptoms was observed in 5%. The annual hemorrhage rate after SRS was 2.4%. Four patients died of rebleeding, and disease-specific survival rate was 86% at 10 years after treatment.
CONCLUSION: Nidus obliteration must be achieved for brainstem AVMs because they possibly cause lethal hemorrhage even after SRS. Treatment with a high margin dose is desirable to obtain favorable outcomes for these lesions. Additional treatment should be considered for an incompletely obliterated nidus.

PMID 21368695  Neurosurgery. 2011 Jul;69(1):45-51; discussion 51-2. do・・・
著者: Tomoyuki Koga, Masahiro Shin, Keisuke Maruyama, Atsuro Terahara, Nobuhito Saito
雑誌名: Neurosurgery. 2010 Aug;67(2):398-403. doi: 10.1227/01.NEU.0000371989.90956.6F.
Abstract/Text BACKGROUND: Arteriovenous malformations (AVMs) in the thalamus carry a high risk of hemorrhage. Although stereotactic radiosurgery (SRS) is widely accepted because of the high surgical morbidity and mortality of these lesions, precise long-term outcomes are largely unknown.
OBJECTIVE: To review our experience with SRS for thalamic AVMs based on the latest follow-up data.
METHODS: Forty-eight patients with thalamic AVMs were treated by SRS using the Leksell Gamma Knife and were followed. Long-term outcomes including the obliteration rate, hemorrhage after treatment, and adverse effects were retrospectively analyzed.
RESULTS: The annual hemorrhage rate before SRS was 14%. The mean follow-up period after SRS was 66 months (range 6-198 months). The actuarial obliteration rate confirmed by angiography was 82% at 5 years after treatment, and the annual hemorrhage rate after SRS was 0.36%. Factors associated with higher obliteration rates were previous hemorrhage (P = .004) and treatment using new planning software (P = .001). Persistent worsening of neurological symptoms was observed in 17% and more frequently seen in patients who were treated using older planning software (P = .04) and a higher margin dose (P = .02). The morbidity rate for patients who received treatment planned using new software with a margin dose not more than 20 Gy was 12%.
CONCLUSION: SRS for thalamic AVMs achieved a high obliteration rate and effectively decreased the risk of hemorrhage, with less morbidity compared with other modalities. Longer follow-up to evaluate the risk of delayed complications and the effort to minimize the morbidity is necessary.

PMID 20644425  Neurosurgery. 2010 Aug;67(2):398-403. doi: 10.1227/01.N・・・
著者: Hirotaka Hasegawa, Shunya Hanakita, Masahiro Shin, Takehiro Sugiyama, Mariko Kawashima, Wataru Takahashi, Masaaki Shojima, Osamu Ishikawa, Hirofumi Nakatomi, Nobuhito Saito
雑誌名: World Neurosurg. 2018 Aug;116:e556-e565. doi: 10.1016/j.wneu.2018.05.038. Epub 2018 May 14.
Abstract/Text OBJECTIVE: Stereotactic radiosurgery is widely used to treat brain arteriovenous malformation; however, detailed information on late radiation-induced complications (LRICs) is scarce. The goal of the present study was to characterize the incidence, risk factors, and clinical outcomes of LRICs based on our long-term follow-up data.
METHODS: The outcomes of consecutive patients who underwent stereotactic radiosurgery for arteriovenous malformations at our institution in 1990-2010 were analyzed. Cyst formation/encapsulated hematoma (CF/EH) and radiation-induced tumor were defined as LRICs. Cumulative incidence rates were calculated using the Kaplan-Meier method. Risk factors for CF/EH were analyzed using a Cox proportional hazard model.
RESULTS: A total of 581 patients with mean and median follow-up periods of 11.8 and 10.1 years, respectively (range, 2.0-26.7 years), were analyzed. CF/EH was observed in 30 patients (5.2%). The median time to progression was 11.8 years (range, 1.9-23.9 years). Cumulative incidence rates were 0.8%, 2.8%, 7.6%, and 9.7% at 5, 10, 15, and 20 years, respectively. A multivariate analysis showed that lobar location and maximal diameter ≥22 mm were significant risk factors for CF/EH. Overall, the functional outcomes were mild, moderate, and severe/fatal in 26 (87%), 1 (3%), and 3 (10%) patients, respectively. Radiation-induced tumor was confirmed in only 1 patient (0.17%).
CONCLUSIONS: An increased nidus size and lobar location are risk factors for CF/EH. Although the CF/EH incidence is low, some LRICs develop after long periods. Extended follow-up is warranted, particularly of patients with risk factors.

Copyright © 2018 Elsevier Inc. All rights reserved.
PMID 29772363  World Neurosurg. 2018 Aug;116:e556-e565. doi: 10.1016/j・・・

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