今日の臨床サポート

脳静脈血栓症

著者: 橋本洋一郎 熊本市立熊本市民病院

監修: 内山真一郎 国際医療福祉大学臨床医学研究センター

著者校正/監修レビュー済:2021/11/10
参考ガイドライン:
  1. Saposnik G, Barinagarrementeria F, Brown RD, Bushnell CD, Cucchiara B, Cushman M, deVeber G, Ferro JM, Tsai FY, American Heart Association Stroke Council and the Council on Epidemiology and Prevention. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke [Internet]. 2011 Apr 1 [cited 2018 Sep 7];42(4):1158–92. Available from: http://stroke.ahajournals.org/cgi/doi/10.1161/STR.0b013e31820a8364 PMID: 21293023
  1. 日本脳卒中学会:脳卒中治療ガイドライン2021ガイドラインpp225-227
  1. Ferro J, Bousser MG, Canhão P, Coutinho JM, Crassard I, Dentali F, di Minno M, Maino A, Martinelli L, Masuhr F, de Sousa DA, Stam J; for the European Stroke Organization: European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis- endorsed by the European Academy of Neurology. Eur Stroke J 2017; 2(3): 195-221.PMID: 31008314
  1. 日本脳卒中学会/日本血栓止血学会アストラゼネカ社COVID-19ワクチン接種後の血小板減少症を伴う血栓症の診断と治療の手引き・第2版(2021年6月)
患者向け説明資料

概要・推奨   

  1. 脳静脈血栓症は脳梗塞と似て非なる症候を呈する。①進行性に増悪すること②症候の動揺③頭蓋内圧亢進症候やけいれんを伴うことが多いこと④両側性病変に伴う症候が多いこと――などであるため、このような特徴を持つ頭痛は積極的に脳静脈血栓症を検査することが推奨される(推奨度2)。
  1. 脳静脈血栓症はCTやMRIにて診断を行う。特に、MRIのT2*強調画像やSWIとMRV、あるいはCTAでまず診断を行い、必要に応じて脳血管造影を行うことが推奨される(推奨度1)。
  1. 頭痛のみあるいは持続時間の長い症例を除いて、脳静脈血栓症の疑いのある患者では神経画像診断の前にD-dimerの測定が推奨される(推奨度2)。
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  1. 脳静脈血栓症や内臓静脈血栓症を来すCOVID-19にワクチン接種後の血小板減少症を伴う血栓症(TTS)では非ヘパリン性抗凝固薬や免疫グロブリン静注療法等を行う(推奨度2、エビデンスランクO、J)[1]。ヘパリンや低分子ヘパリンは用いない(推奨度4、エビデンスランクO、J)[1]
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:
橋本洋一郎 : 講演料(第一三共株式会社,ファイザー株式会社,バイエル薬品株式会社,大塚製薬株式会社)[2021年]
監修:内山真一郎 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 日本脳卒中学会の脳卒中治療ガイドライン2015が脳卒中治療ガイドライン2021に改訂された。ワルファリンの継続期間と開頭減圧術についての追加記載が行われ、グリセロールの記載が削除された。ただし今までの推奨を変更する必要はない。
  1. 脳静脈血栓症や内臓静脈血栓症を来すCOVID-19にワクチン接種後の血小板減少症を伴う血栓症(TTS)という新たな疾患が登場し、従来の脳静脈血栓症の治療とは違った治療法が必要になった(ヘパリンを中心とする治療法では病態を悪化させる可能性が高く、非ヘパリン性抗凝固薬や免疫グロブリン静注療法等を行う)。

病態・疫学・診察

診断のポイント  
  1. 脳静脈血栓症の臨床症候は多様で、かつ特異的なものがないが、
  1. 頭蓋内圧亢進症候(頭痛、悪心・嘔吐、乳頭浮腫、外転神経麻痺)
  1. 脳局在症候、
  1. 海綿静脈洞症候群
  1. 亜急性脳症
などを呈する。
  1. 頭痛で初発することが多い。その特徴(進行性、症状の動揺があること、臥位で増悪、立位で軽減すること、鎮痛薬の効果が乏しいこと)も知っておく必要がある。
  1. けいれんや局在症候で発症するものもあるが、脳症を来す疾患を鑑別しなければならない場合もある。
  1. 脳梗塞との違いは、
  1. 進行性に増悪すること
  1. 症候の動揺
  1. 頭蓋内圧亢進症候やけいれんを伴うことが多いこと
  1. 両側性病変に伴う症候が多いこと
などである。
  1. 全脳卒中の0.5~1%程度が脳静脈血栓症である(脳静脈血栓症は忘れたころにやって来る!)。
  1. CTで脳静脈の血栓を検出できる場合がある。MRI(特にT2*強調画像やSWI)、MRV(magnetic resonance venography)が行えない場合にはCTV(CT venography)を行う。
  1. MRIでは静脈のflow voidの消失、さらにT2*強調画像での静脈内血栓の描出、MRVでの静脈洞閉塞などにより、脳静脈血栓症の診断を行う。
  1. CTVやMRVで確定できない場合には脳血管造影を行う。
  1. 同時に、原因疾患検索のための検査を行う。経口避妊薬、血栓形成促進効果のある薬剤、妊娠や産褥、感染症(特に中枢神経、副鼻腔、耳、乳様突起を巻き込む)などの一過性の原因(危険因子)、遺伝的血栓性疾患、抗りん脂質抗体症候群、骨髄増殖性疾患、悪性疾患などの全身性の血栓性状態のような永久危険因子の2つに分けられる[2]。成人の脳静脈血栓症の13%は原因不明である。
 
  1. 脳静脈血栓症は脳梗塞と似て非なる症候を呈する。①進行性に増悪すること②症候の動揺③頭蓋内圧亢進症候やけいれんを伴うことが多いこと④両側性病変に伴う症候が多いこと――などであるため、このような特徴を持つ頭痛は積極的に脳静脈血栓症を検査することが推奨される(推奨度2)。<図表>
  1. 脳静脈血栓症の臨床症候は多様で、かつ特異的なものがないが、
  1. 頭蓋内圧亢進症候(頭痛、悪心・嘔吐、乳頭浮腫、外転神経麻痺)
  1. 脳局在症候
  1. 海綿静脈洞症候群
  1. 亜急性脳症
  1. などを呈する[3][4][5]
  1. 頭痛で初発することが多い。その特徴も知っておく必要がある。
  1. けいれんや局在症候で発症するものもあるが、脳症を来す疾患を鑑別しなければならない場合もある。
  1. 脳梗塞との違いは、
  1. 進行性に増悪すること
  1. 症候の動揺
  1. 頭蓋内圧亢進症候やけいれんを伴うことが多いこと
  1. 両側性病変に伴う症候が多いこと
  1. などである。
病歴・診察のポイント  
  1. 血栓・塞栓症の既往歴、家族歴について聴取する。

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11月30日(火)までにお申込みいただくと、
通常12ヵ月の使用期間が2ヶ月延長となり、14ヵ月ご利用いただけるようになります。

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文献 

著者: José M Ferro, Marie-Germaine Bousser, Patrícia Canhão, Jonathan M Coutinho, Isabelle Crassard, Francesco Dentali, Matteo di Minno, Alberto Maino, Ida Martinelli, Florian Masuhr, Diana Aguiar de Sousa, Jan Stam, European Stroke Organization
雑誌名: Eur Stroke J. 2017 Sep;2(3):195-221. doi: 10.1177/2396987317719364. Epub 2017 Jul 21.
Abstract/Text The current proposal for cerebral venous thrombosis guideline followed the Grading of Recommendations, Assessment, Development, and Evaluation system, formulating relevant diagnostic and treatment questions, performing systematic reviews of all available evidence and writing recommendations and deciding on their strength on an explicit and transparent manner, based on the quality of available scientific evidence. The guideline addresses both diagnostic and therapeutic topics. We suggest using magnetic resonance or computed tomography angiography for confirming the diagnosis of cerebral venous thrombosis and not screening patients with cerebral venous thrombosis routinely for thrombophilia or cancer. We recommend parenteral anticoagulation in acute cerebral venous thrombosis and decompressive surgery to prevent death due to brain herniation. We suggest to use preferentially low-molecular weight heparin in the acute phase and not using direct oral anticoagulants. We suggest not using steroids and acetazolamide to reduce death or dependency. We suggest using antiepileptics in patients with an early seizure and supratentorial lesions to prevent further early seizures. We could not make recommendations due to very poor quality of evidence concerning duration of anticoagulation after the acute phase, thrombolysis and/or thrombectomy, therapeutic lumbar puncture, and prevention of remote seizures with antiepileptic drugs. We suggest that in women who suffered a previous cerebral venous thrombosis, contraceptives containing oestrogens should be avoided. We suggest that subsequent pregnancies are safe, but use of prophylactic low-molecular weight heparin should be considered throughout pregnancy and puerperium. Multicentre observational and experimental studies are needed to increase the level of evidence supporting recommendations on the diagnosis and management of cerebral venous thrombosis.

PMID 31008314  Eur Stroke J. 2017 Sep;2(3):195-221. doi: 10.1177/23969・・・
著者: Gustavo Saposnik, Fernando Barinagarrementeria, Robert D Brown, Cheryl D Bushnell, Brett Cucchiara, Mary Cushman, Gabrielle deVeber, Jose M Ferro, Fong Y Tsai, American Heart Association Stroke Council and the Council on Epidemiology and Prevention
雑誌名: Stroke. 2011 Apr;42(4):1158-92. doi: 10.1161/STR.0b013e31820a8364. Epub 2011 Feb 3.
Abstract/Text BACKGROUND: The purpose of this statement is to provide an overview of cerebral venous sinus thrombosis and to provide recommendations for its diagnosis, management, and treatment. The intended audience is physicians and other healthcare providers who are responsible for the diagnosis and management of patients with cerebral venous sinus thrombosis.
METHODS AND RESULTS: Members of the panel were appointed by the American Heart Association Stroke Council's Scientific Statement Oversight Committee and represent different areas of expertise. The panel reviewed the relevant literature with an emphasis on reports published since 1966 and used the American Heart Association levels-of-evidence grading algorithm to rate the evidence and to make recommendations. After approval of the statement by the panel, it underwent peer review and approval by the American Heart Association Science Advisory and Coordinating Committee.
CONCLUSIONS: Evidence-based recommendations are provided for the diagnosis, management, and prevention of recurrence of cerebral venous thrombosis. Recommendations on the evaluation and management of cerebral venous thrombosis during pregnancy and in the pediatric population are provided. Considerations for the management of clinical complications (seizures, hydrocephalus, intracranial hypertension, and neurological deterioration) are also summarized. An algorithm for diagnosis and management of patients with cerebral venous sinus thrombosis is described.

PMID 21293023  Stroke. 2011 Apr;42(4):1158-92. doi: 10.1161/STR.0b013e・・・
著者: K Koopman, M Uyttenboogaart, P C Vroomen, J van der Meer, J De Keyser, G J Luijckx
雑誌名: J Neurol Sci. 2009 Jan 15;276(1-2):66-8. doi: 10.1016/j.jns.2008.08.033. Epub 2008 Sep 26.
Abstract/Text BACKGROUND AND PURPOSE: Cerebral venous thrombosis (CVT) is a rare disease with a variable outcome. The aim of this study was to develop and validate a predictive outcome score for CVT patients.
METHODS: The score was based on the 8 predictive variables of poor outcome (modified Rankin Scale score>2) from the International Study on Cerebral Vein and Dural Sinus Thrombosis: age >37, male, mental status disorder, coma, intracranial hemorrhage, deep CVT, CNS infection, and malignancy. To assign a weighted index (WI), the natural logarithm of the hazard ratio of each variable was calculated, multiplied by 10 and rounded to the nearest integer. The individual score of each patient was the sum of the WI. The validation sample consisted of a retrospective single center cohort of 90 CVT patients.
RESULTS: Sixteen patients (18%) had a poor outcome. The predictive score had an area under the receiver operating characteristic curve of 0.81 (95% CI 0.71-0.90). The cut-off score with the maximum sum of sensitivity and specificity was a score> or =14 with sensitivity of 88% (81%-95%) and specificity of 70% (61%-79%). The predictive value of a score<14 for good outcome was 96% (92%-100%), whereas the predictive value of a score> or =14 for poor outcome was 39% (29%-49%).
CONCLUSIONS: This relatively simple predictive outcome score may be useful in CVT patients. A cut-off score of 14 reliably predicts good outcome, but is less accurate in predicting poor outcome.

PMID 18823637  J Neurol Sci. 2009 Jan 15;276(1-2):66-8. doi: 10.1016/j・・・
著者: K M Einhäupl, A Villringer, W Meister, S Mehraein, C Garner, M Pellkofer, R L Haberl, H W Pfister, P Schmiedek
雑誌名: Lancet. 1991 Sep 7;338(8767):597-600.
Abstract/Text Treatment of sinus venous thrombosis (SVT) is controversial. Although heparin has been used for this condition, many investigators have opposed its use because of the frequent occurrence of intracranial haemorrhage (ICH) and SVT. Therefore we have evaluated anticoagulation with adjusted-dose intravenous heparin for treatment of aseptic SVT in a randomised, blinded (patient and observer), placebo-controlled study in 20 patients (10 heparin, 10 placebo). The clinical course of the two groups, as judged by a newly designed SVT-severity scale, started to differ in favour of the heparin group after 3 days of treatment (p less than 0.05, Mann-Whitney U-test) and the difference remained significant (p less than 0.01) after 8 days of treatment. After 3 months, 8 of the heparin-treated patients had a complete clinical recovery and 2 had slight residual neurological deficits. In the placebo group, only 1 patient had a complete recovery, 6 patients had neurological deficits, and 3 patients died (p less than 0.01, modified Fisher's exact test). An additional retrospective study on the relation between heparin treatment and ICH in SVT patients was based on 102 patients, 43 of whom had an ICH. 27 of these patients were treated with dose-adjusted, intravenous heparin after the ICH. Of these 27 patients, 4 died (mortality 15%), and 14 patients completely recovered. Of the 13 patients that did not receive heparin after ICH, 9 died (mortality 69%) and only 3 patients completely recovered. We conclude that anticoagulation with dose-adjusted intravenous heparin is an effective treatment in patients with SVT and that ICH is not a contraindication to heparin treatment in these patients.

PMID 1679154  Lancet. 1991 Sep 7;338(8767):597-600.
著者: S F de Bruijn, J Stam
雑誌名: Stroke. 1999 Mar;30(3):484-8.
Abstract/Text BACKGROUND AND PURPOSE: Treatment of cerebral sinus thrombosis with heparin is controversial. We conducted a double-blind, placebo-controlled multicenter trial to examine whether anticoagulant treatment improves outcome in patients with sinus thrombosis.
METHODS: Patients were randomized between body weight-adjusted subcutaneous nadroparin (180 anti-factor Xa units/kg per 24 hours) and matching placebo for 3 weeks (double-blind part of trial), followed by 3 months of oral anticoagulants for patients allocated nadroparin (open part). Patients with cerebral hemorrhage caused by sinus thrombosis were also included.
RESULTS: Sixty patients were enrolled, and none were lost to follow-up. In 1 patient the diagnosis proved wrong after randomization. After 3 weeks, 6 of 30 patients (20%) in the nadroparin group and 7 of 29 patients (24%) in the placebo group had a poor outcome, defined as death or Barthel Index score of <15 (risk difference, -4%; 95% CI, -25 to 17%; NS). After 12 weeks, 4 of 30 patients (13%) in the nadroparin group and 6 of 29 (21%) in the placebo group had a poor outcome, defined as death or Oxford Handicap Score of >/=3 (risk difference, -7%; 95% CI, -26% to 12%; NS). There were no new symptomatic cerebral hemorrhages. One patient in the nadroparin group had a major gastrointestinal hemorrhage, and 1 patient in the placebo group died from clinically suspected pulmonary embolism.
CONCLUSIONS: Patients with cerebral sinus thrombosis treated with anticoagulants (low-molecular-weight heparin followed by oral anticoagulation) had a favorable outcome more often than controls, but the difference was not statistically significant. Anticoagulation proved to be safe, even in patients with cerebral hemorrhage.

PMID 10066840  Stroke. 1999 Mar;30(3):484-8.
著者: K Einhäupl, J Stam, M-G Bousser, S F T M De Bruijn, J M Ferro, I Martinelli, F Masuhr, European Federation of Neurological Societies
雑誌名: Eur J Neurol. 2010 Oct;17(10):1229-35. doi: 10.1111/j.1468-1331.2010.03011.x.
Abstract/Text BACKGROUND: Cerebral venous and sinus thrombosis (CVST) is a rather rare disease which accounts for <1% of all strokes. Diagnosis is still frequently overlooked or delayed as a result of the wide spectrum of clinical symptoms and the often subacute or lingering onset. Current therapeutic measures which are used in clinical practice include the use of anticoagulants such as dose-adjusted intravenous heparin or body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH), the use of thrombolysis and symptomatic therapy including control of seizures and elevated intracranial pressure.
METHODS: We searched MEDLINE (National Library of Medicine), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Library to review the strength of evidence to support these interventions and the preparation of recommendations on the therapy of CVST based on the best available evidence. Review articles and book chapters were also included. Recommendations were reached by consensus. Where there was a lack of evidence but consensus was clear we stated our opinion as good practice points.
RESULTS AND CONCLUSIONS: Patients with CVST without contraindications for anticoagulation (AC) should be treated either with body weight-adjusted subcutaneous LMWH or with dose-adjusted intravenous heparin (level B recommendation). Concomitant intracranial haemorrhage (ICH) related to CVST is not a contraindication for heparin therapy. The optimal duration of oral anticoagulant therapy after the acute phase is unclear. Oral AC may be given for 3 months if CVST was secondary to a transient risk factor, for 6-12 months in patients with idiopathic CVST and in those with "mild" thrombophilia, such as heterozygous factor V Leiden or prothrombin G20210A mutation and high plasma levels of factor VIII. Indefinite AC should be considered in patients with recurrent episodes of CVST and in those with one episode of CVST and 'severe' thrombophilia, such as antithrombin, protein C or protein S deficiency, homozygous factor V Leiden or prothrombin G20210A mutation, antiphospholipid antibodies and combined abnormalities (good practice point). There is insufficient evidence to support the use of either systemic or local thrombolysis in patients with CVST. If patients deteriorate despite adequate AC and other causes of deterioration have been ruled out, thrombolysis may be a therapeutic option in selected cases, possibly in those without large ICH and threatening herniation (good practice point). There are no controlled data about the risks and benefits of certain therapeutic measures to reduce an elevated intracranial pressure (with brain displacement) in patients with severe CVST. However, in severe cases with impending herniation craniectomy can be used as a life-saving intervention (good practice point).

© 2010 The Author(s). European Journal of Neurology © 2010 EFNS.
PMID 20402748  Eur J Neurol. 2010 Oct;17(10):1229-35. doi: 10.1111/j.1・・・
著者: J Stam, S F De Bruijn, G DeVeber
雑誌名: Cochrane Database Syst Rev. 2002;(4):CD002005. doi: 10.1002/14651858.CD002005.
Abstract/Text BACKGROUND: Treatment of cerebral sinus thrombosis with anticoagulants has been controversial. Anticoagulants may prevent new venous infarcts, neurologic deterioration, and pulmonary embolism but may also promote haemorrhages.
OBJECTIVES: To review the available evidence regarding the effectiveness and safety of anticoagulant therapy in patients with confirmed cerebral sinus thrombosis.
SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched 18 March 2002). We also searched MEDLINE (1966-Oct 2001), EMBASE (1980-Feb 2002) and the Cochrane Controlled Trials Register (Cochrane Library, 2002 Issue 1) and contacted authors to identify additional published and unpublished studies.
SELECTION CRITERIA: Unconfounded randomised controlled trials in which anticoagulant therapy was compared with placebo or open control in patients with cerebral sinus thrombosis (confirmed by intra-arterial contrast or magnetic resonance angiography).
DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted outcomes for each of the two treatment groups (anticoagulant treatment and control). The outcome data for each patient are analysed in the treatment group to which the patient was originally allocated ('intention to treat' analysis). A weighted estimate of the treatment effects across trials (relative risk, absolute risk reduction) is calculated using the Cochrane statistical software.
MAIN RESULTS: Two small trials involving 79 patients fulfilled the inclusion criteria. One trial (20 patients) examined the efficacy of intravenous, adjusted dose unfractionated heparin. The other trial (59 patients) examined high dose, body weight adjusted, subcutaneous, low-molecular weight heparin (Nadroparin). Anticoagulant therapy was associated with a pooled relative risk of death of 0.33 (95 % CI 0.08 to 1.21) and of death or dependency of 0.46 (95 % CI 0.16 to 1.31). No new symptomatic intracerebral haemorrhages were observed. One major gastro-intestinal haemorrhage occurred after anticoagulant treatment. Two control patients (placebo) had a diagnosis of probable pulmonary embolism (one fatal).
REVIEWER'S CONCLUSIONS: Based upon the limited evidence available, anticoagulant treatment for cerebral sinus thrombosis appeared to be safe and was associated with a potentially important reduction in the risk of death or dependency which did not reach statistical significance.

PMID 12519565  Cochrane Database Syst Rev. 2002;(4):CD002005. doi: 10.・・・
著者: Jonathan Coutinho, Sebastiaan Ftm de Bruijn, Gabrielle Deveber, Jan Stam
雑誌名: Cochrane Database Syst Rev. 2011 Aug 10;(8):CD002005. doi: 10.1002/14651858.CD002005.pub2. Epub 2011 Aug 10.
Abstract/Text BACKGROUND: Treatment of cerebral venous sinus thrombosis with anticoagulants has been controversial. Anticoagulants may prevent new venous infarcts, neurologic deterioration and pulmonary embolism but may also promote haemorrhages.
OBJECTIVES: To assess the effectiveness and safety of anticoagulant therapy in patients with confirmed cerebral venous sinus thrombosis.
SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched August 2010), MEDLINE (1950 to August 2010), EMBASE (1980 to August 2010) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2011 Issue 1). In an effort to identify further published, unpublished and ongoing trials we searched ongoing trials registers and reference lists of relevant articles, and contacted authors.
SELECTION CRITERIA: Unconfounded randomised controlled trials in which anticoagulant therapy was compared with placebo or open control in patients with cerebral venous sinus thrombosis (confirmed by intra-arterial contrast, or venography with magnetic resonance, or venography with computed tomography imaging).
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted outcomes for each of the two treatment groups (anticoagulant treatment and control). The outcome data for each patient were analysed in the treatment group to which the patient was originally allocated (intention-to-treat analysis). We calculated a weighted estimate of the treatment effects across trials (relative risk, absolute risk reduction).
MAIN RESULTS: We included two small trials involving 79 patients. One trial (20 patients) examined the efficacy of intravenous, adjusted dose unfractionated heparin. The other trial (59 patients) examined high dose, body weight adjusted, subcutaneous, low-molecular weight heparin (nadroparin). Anticoagulant therapy was associated with a pooled relative risk of death of 0.33 (95% confidence interval (CI) 0.08 to 1.21) and of death or dependency of 0.46 (95% CI 0.16 to 1.31). The absolute reduction in the risk of death or dependency was 13% (95% CI 30% to -3%). No new symptomatic intracerebral haemorrhages were observed. One major gastro-intestinal haemorrhage occurred after anticoagulant treatment. Two control patients (placebo) had a diagnosis of probable pulmonary embolism (one fatal).
AUTHORS' CONCLUSIONS: Based upon the limited evidence available, anticoagulant treatment for cerebral venous sinus thrombosis appeared to be safe and was associated with a potentially important reduction in the risk of death or dependency which did not reach statistical significance.

PMID 21833941  Cochrane Database Syst Rev. 2011 Aug 10;(8):CD002005. d・・・
著者: D M Wingerchuk, E F Wijdicks, J R Fulgham
雑誌名: Cerebrovasc Dis. 1998 Jan-Feb;8(1):25-30.
Abstract/Text BACKGROUND AND PURPOSE: Anticoagulation (AC) may improve outcome in cerebral venous thrombosis (CVT), even when complicated by pretreatment hemorrhagic infarction (HI). The HI characteristics which affect the decision to initiate AC therapy and its outcome are unknown. We reviewed our experience with AC treatment for patients with CVT and HI.
METHODS: Retrospective study.
RESULTS: Two groups of patients were compared: those who received AC (n = 6) and those who did not (n = 6). Hemorrhage volumes ranged from petechial to large (93 cm3) hematoma with mass effect. Anticoagulated patients received treatment a mean of 11.3 days after symptom onset. Each had exclusively extratemporal HI without midline shift and had stable hemorrhage volumes and clinical status for at least 24 h prior to AC. AC did not increase HI volume or worsen clinical outcome. All 6 non-AC patients had enlarging hematomas. Four of these 6 patients had temporal HI; and two required hematoma resection.
CONCLUSIONS: AC therapy was avoided in CVT patients with HI that were located in the temporal lobe, caused midline shift or were enlarging. AC was safely initiated within several days in clinically stable patients with non-temporal-lobe HI of unchanging volume. We suggest that the location and unchanged volume on serial CT may be important factors influencing the safety of AC therapy in patients with CVT and HI.

PMID 9645978  Cerebrovasc Dis. 1998 Jan-Feb;8(1):25-30.
著者: Patricia Canhão, Filipa Falcão, José M Ferro
雑誌名: Cerebrovasc Dis. 2003;15(3):159-66. doi: 68833.
Abstract/Text BACKGROUND AND PURPOSE: The use of thrombolytics is frequently mentioned in patients with cerebral venous or dural sinus thrombosis (CVDST) who deteriorate despite anticoagulant therapy. The aim of this review was to collect all the published information about their use in CVDST and to assess their efficacy and safety.
METHODS: To find cases of CVDST treated with thrombolytics, we performed a MEDLINE search from 1966 to July 2001, checked all reference lists of studies found and hand searched volumes of 11 journals. Data was extracted by means of a standardised data extraction form. Proportions and 95% confidence intervals (CI) were calculated for outcomes and complications of thrombolytics. Cases were stratified according to variables that may influence the outcome and subgroups were compared by odds ratios and 95% CI.
RESULTS: No randomised clinical trial (RCT) was found. Seventy-two studies (169 patients) were included. Urokinase was the thrombolytic most frequently administered (76%). In the majority of cases the thrombolytic was locally infused in the occluded sinus (88%). At discharge, 10 cases (7%; 95% CI 3-12%) were dependent and 9 cases (5%; 95% CI 2-9%) died. Intracranial haemorrhages occurred in 17% of cases. In 5% they were associated with clinical deterioration. Extracranial haemorrhages occurred in 21%, but only 2% required blood transfusion.
CONCLUSIONS: Thrombolytics appeared to be reasonably safe in CVDST, but its efficacy cannot be assessed from the published data. Considering that CVDST is an uncommon disease, a randomised controlled trial to assess effectiveness and safety of local thrombolytics in cases of CVDST with poor prognosis is difficult but not impossible to undertake, on a multicentre international collaboration trial.

Copyright 2003 S. Karger AG, Basel
PMID 12646773  Cerebrovasc Dis. 2003;15(3):159-66. doi: 68833.
著者: A Ciccone, P Canhão, F Falcão, J M Ferro, R Sterzi
雑誌名: Cochrane Database Syst Rev. 2004;(1):CD003693. doi: 10.1002/14651858.CD003693.pub2.
Abstract/Text BACKGROUND: Treatment of cerebral sinus thrombosis with thrombolytics has been reported in cases with a deteriorating clinical course despite anticoagulant therapy. The rationale of this treatment is to promote rapid recanalisation of the occluded sinus.
OBJECTIVES: To review the available evidence on the efficacy and safety of thrombolysis in confirmed cerebral sinus thrombosis.
SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (March 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2003), MEDLINE (1966 to March 2003), EMBASE (1980 to March 2003), and reference lists of all relevant publications.
SELECTION CRITERIA: We aimed to analyse separately unconfounded randomised controlled trials comparing thrombolytic agent with placebo, or thrombolytic agent with antithrombotic therapy, or thrombolytic agent and antithrombotic with antithrombotic alone, in patients with dural sinus thrombosis (confirmed by MR venography, intra-arterial venography or CT venography).
DATA COLLECTION AND ANALYSIS: Two groups of reviewers independently applied the inclusion criteria.
MAIN RESULTS: No randomised controlled trials were found.
REVIEWER'S CONCLUSIONS: There is currently no available evidence from randomised controlled trials regarding the efficacy or safety of thrombolytic therapy in dural sinus thrombosis. A randomised controlled trial is justified to test this therapy especially in patients predicted to have a poor prognosis.

PMID 14974030  Cochrane Database Syst Rev. 2004;(1):CD003693. doi: 10.・・・
著者: J L Frey, G J Muro, C G McDougall, B L Dean, H K Jahnke
雑誌名: Stroke. 1999 Mar;30(3):489-94.
Abstract/Text BACKGROUND AND PURPOSE: We chose to evaluate the safety and efficacy of combined intrathrombus rtPA and intravenous heparin in cerebral venous thrombosis (CVT).
METHODS: We treated 12 patients with symptoms of 1 to 40 days' duration (eg, headache, somnolence, focal deficits, seizures, and nausea and vomiting). Pretreatment MRI disclosed subtle hemorrhagic venous infarction in 4 patients, obvious hemorrhagic infarction in 2, small parenchymal hemorrhage from recent pallidotomy in 1, and no focal lesion in 5. Magnetic resonance venography and contrast venography identified thrombi in the superior sagittal sinus (SSS) in 3 patients; transverse/sigmoid sinus (TS/SS) in 2; SSS and both TS/SS in 1; SSS and 1 TS/SS in 5; and SSS, 1 TS/SS, and straight sinus in 1 patient. A loading dose of rtPA was instilled throughout the clot at 1 mg/cm, followed by continuous intrathrombus infusion at 1 to 2 mg/h. Intravenous heparin was infused concomitantly.
RESULTS: Flow was restored completely in 6 patients and partially in 3, with a mean rtPA dose of 46 mg (range, 23 to 128 mg) at a mean time of 29 hours (range, 13 to 77 hours). Symptoms improved in these 9 patients concomitantly with flow restoration. Flow could not be restored in 3 patients. In 1 of them, treatment was stopped when little progress had been made, and fibrinogen level dropped to 118 mg/dL. In the other 2 patients, hemorrhagic worsening occurred, and treatment was abbreviated after initial rtPA dosing. In 1 of these, the hematoma was evacuated.
CONCLUSIONS: Our experience with intrathrombus rtPA in conjunction with intravenous heparin in patients with CVT is encouraging. This therapy should probably be regarded as unsafe in patients with obvious hemorrhage. Time to restore flow may be faster than with urokinase (an average of 71 hours has been reported for 29 documented patients). Further evaluation of rtPA with heparin in CVT is warranted.

PMID 10066841  Stroke. 1999 Mar;30(3):489-94.
著者: Seon-Kyu Lee, Maxim Mokin, Steven W Hetts, Johanna T Fifi, Marie-Germaine Bousser, Justin F Fraser, Society of NeuroInterventional Surgery
雑誌名: J Neurointerv Surg. 2018 Aug;10(8):803-810. doi: 10.1136/neurintsurg-2018-013973. Epub 2018 Jun 5.
Abstract/Text
PMID 29871990  J Neurointerv Surg. 2018 Aug;10(8):803-810. doi: 10.113・・・
著者: Adeel Ilyas, Ching-Jen Chen, Daniel M Raper, Dale Ding, Thomas Buell, Panogiotis Mastorakos, Kenneth C Liu
雑誌名: J Neurointerv Surg. 2017 Nov;9(11):1086-1092. doi: 10.1136/neurintsurg-2016-012938. Epub 2017 Feb 17.
Abstract/Text BACKGROUND: Cerebral venous sinus thrombosis (CVST) is an uncommon form of stroke that, when severe, can be a therapeutic challenge. Endovascular mechanical thrombectomy (EMT) techniques have significantly evolved over the past decade, but data regarding the efficacy and safety of EMT for CVST are poorly defined.
OBJECTIVE: To summarize the large number of case series on this relatively rare condition and establish trends in the outcomes of EMT for CVST.
METHODS: A literature review was performed using PubMed and Medline to identify reports of three or more patients with CVST treated with EMT. Baseline and outcomes data, including radiographic resolution, neurological outcome, recurrence, and treatment-related complications, were extracted for analysis.
RESULTS: A total of 17 studies comprising 235 patients treated with EMT were included for analysis. Based on pooled data, 40.2% of patients presented with encephalopathy or coma. Concurrent endovascular thrombolysis was employed in 87.6% of patients. Complete radiographic resolution of CVST was achieved in 69.0% of patients. At follow-up (range 0.5-3.5 years), 34.7% of patients were neurologically intact and the mortality rate was 14.3%. CVST recurrence was evident in 1.2%. Worsening or new intracranial hemorrhage (ICH) occurred in 8.7% of cases. ORs of good outcome (modified Rankin Scale score 0-2) and development of ICH with sole EMT versus concurrent thrombolytic therapy were 1.51 (95% CI 0.29 to 8.15, p=0.61) and 1.15 (95% CI 0.12 to 10.80, p=0.90), respectively.
CONCLUSIONS: EMT is an effective salvage therapy for refractory CVST, with a reasonable safety profile. Chemical thrombolysis, in conjunction with EMT, did not appear to result in additional harm or benefit. Further analysis is warranted to determine predictors of success after EMT for CVST.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
PMID 28213478  J Neurointerv Surg. 2017 Nov;9(11):1086-1092. doi: 10.1・・・
著者: José M Ferro, Isabelle Crassard, Jonathan M Coutinho, Patrícia Canhão, Fernando Barinagarrementeria, Brett Cucchiara, Laurent Derex, Christoph Lichy, Jaime Masjuan, Ayrton Massaro, Gonzalo Matamala, Sven Poli, Mohammad Saadatnia, Erwin Stolz, Miguel Viana-Baptista, Jan Stam, Marie-Germaine Bousser, Second International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT 2) Investigators
雑誌名: Stroke. 2011 Oct;42(10):2825-31. doi: 10.1161/STROKEAHA.111.615393. Epub 2011 Jul 28.
Abstract/Text BACKGROUND AND PURPOSE: Herniation attributable to unilateral mass effect is the major cause of death in cerebral venous thrombosis (CVT). Decompressive surgery may be lifesaving in these patients.
METHODS: Retrospective registry of cases of acute CVT treated with decompressive surgery (craniectomy or hematoma evacuation) in 22 centers and systematic review of all published cases of CVT treated with decompressive surgery. The primary outcome was the score on the modified Rankin Scale (mRS) score at last follow-up, dichotomized between favorable (mRS score, 0-4) and unfavorable outcome (mRS score, 5 or death). Secondary outcomes were complete recovery (mRS score 0-1), independence (mRS score, 0-2), severe dependence (mRS score, 4-5), and death at last available follow-up.
RESULTS: Sixty-nine patients were included and 38 were from the registry. Decompressive craniectomy was performed in 45 patients, hematoma evacuation was performed in 7, and both interventions were performed in 17 patients. At last follow-up (median, 12 months) only 12 (17.4%) had un unfavorable outcome. Twenty-six (37.7%) had mRS score 0 to 1, 39 (56.5%) had mRS score 0 to 2, 4 (5.8%) were alive with mRS score 4 to 5, and 11 (15.9%) patients died. Three of the 9 patients with bilateral fixed pupils recovered completely. Comatose patients were less likely to be independent (mRS score 0-2) than noncomatose patients (45% versus 84%; P=0.003). Patients with bilateral lesions were more likely to have unfavorable outcomes (50% versus 11%; P=0.004) and to die (42% versus 11%; P=0.025).
CONCLUSIONS: In CVT patients with large parenchymal lesions causing herniation, decompressive surgery was lifesaving and often resulted in good functional outcome, even in patients with severe clinical conditions.

PMID 21799156  Stroke. 2011 Oct;42(10):2825-31. doi: 10.1161/STROKEAHA・・・
著者: J Kwan, A Guenther
雑誌名: Cochrane Database Syst Rev. 2006 Jul 19;(3):CD005501. doi: 10.1002/14651858.CD005501.pub2. Epub 2006 Jul 19.
Abstract/Text BACKGROUND: Intracranial venous thrombosis (ICVT) commonly presents with seizures in the acute period, and some patients may develop recurrent seizures in the long term. The prophylactic use of antiepileptic drugs (AEDs) for the management of post-ICVT seizures is controversial and there is currently no consensus on the optimal management of post-ICVT seizures.
OBJECTIVES: To assess the effects of AEDs for the primary and secondary prevention of seizures related to ICVT.(1) Do AEDs reduce the likelihood of seizures in patients who have had an ICVT but have not had a seizure?(2) Do AEDs reduce the likelihood of further seizures in patients who have had an ICVT and at least one seizure?
SEARCH STRATEGY: We aimed to identify relevant studies in the Cochrane Epilepsy Group and Cochrane Stroke Group Trials Registers. We also undertook specialised searches of the Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE, and checked the reference lists of articles retrieved from the searches.
SELECTION CRITERIA: We considered all randomised and quasi-randomised controlled trials in which patients were assigned to a treatment group (that is, receiving at least one AED) or control group (receiving placebo or no drug).
DATA COLLECTION AND ANALYSIS: Both review authors independently screened and assessed the methodological quality of the studies. If studies had been included, then one review author would have extracted the data and the other would have checked the extracted data.
MAIN RESULTS: No relevant studies were found.
AUTHORS' CONCLUSIONS: There is no evidence to support or refute the use of antiepileptic drugs for the primary or secondary prevention of seizures related to intracranial venous thrombosis. Well-designed randomised controlled trials are urgently needed to inform practice.

PMID 16856099  Cochrane Database Syst Rev. 2006 Jul 19;(3):CD005501. d・・・
著者: Gabriel R de Freitas, Julien Bogousslavsky
雑誌名: Front Neurol Neurosci. 2008;23:23-54. doi: 10.1159/0000111259.
Abstract/Text The risk factors for deep venous thrombosis (and for cerebral vein and sinus thrombosis, CVST) differ from those for arterial disease. The risk factors for venous thrombosis are linked to the Virchow triad of stasis of the blood, changes in the vessel wall, and changes in the composition of the blood, especially the first and third of these. Risk factors are usually divided into acquired (e.g. surgery, trauma, pregnancy, puerperium, lupus anticoagulant, malignant disease, and female hormones) and genetic (congenital thrombophilia). However, the separation of genetic and acquired risk factors is somewhat artificial, since they have additive effects and venous thrombosis is often multifactorial. In this review, we discuss acquired risk factors for CVST. These include hormonal changes (e.g. oral contraceptives use, hormone replacement therapy, pregnancy and puerperium), mechanical precipitants (e.g. head trauma, jugular catheterization, surgery, lumbar puncture), local and generalized infections, cancer, acquired prothrombotic states (e.g. hyperhomocysteinemia, nephrotic syndrome), inflammatory diseases (e.g. vaculitis, intestinal inflammatory disease), hematological disorders, neurological diseases (e.g. dural arteriovenous malformations, spontaneous intracranial hypotension), drugs and other situations. However, only some conditions are consistently present in case series, while many appear only in anecdotal reports. Thus, in most situations, a causal link cannot be established. Determining a cause-and-effect relationship is essential for developing preventive, diagnostic, and therapeutic strategies. Therefore, further multicentered, case-controlled studies are crucial for better understanding the pathogenesis of CVST.

PMID 18004052  Front Neurol Neurosci. 2008;23:23-54. doi: 10.1159/0000・・・

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