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A Patient with Deep Cerebral Venous Sinus Thrombosis in whom Neuroendovascular Therapy was Effective
Case Report
A Patient with Deep Cerebral Venous Sinus Thrombosis in whom Neuroendovascular Therapy was Effective Ichiro Deguchi, MD,* Tomohisa Dembo, MD,* Yuji Kato, MD,* Fumitaka Yamane, MD,† Shoichiro Ishihara, MD,† and Norio Tanahashi, MD*
A 63-year-old man presented with aphasia. A computed tomographic scan of the head revealed hemorrhagic infarction in the left temporal lobe. Magnetic resonance venography (MRV) revealed no flow from the straight sinus and left transverse sinus to the sigmoid sinus, indicating cerebral venous sinus thrombosis (CVST). Because of rapidly deteriorating consciousness despite heparin infusion, neuroendovascular therapy was performed, recanalization was achieved, and the level of consciousness improved. In Western countries, neuroendovascular therapy is often aggressively performed in patients with worsening symptoms despite anticoagulation. However, in Japan, such reports are extremely rare. We recommend neuroendovascular therapy for deep CVST resistant to anticoagulant therapy. Key Words: Deep cerebral venous sinus thrombosis—neuroendovascular therapy—resistant to anticoagulant therapy. Ó 2012 by National Stroke Association
Cerebral venous sinus thrombosis (CVST) accounts for 0.5% to 1.0% of all strokes,1 and with the introduction of computed tomographic (CT) and magnetic resonance imaging (MRI) scans and other advances in technology, a considerable number of cases are now being seen in clinical practice. Anticoagulation (AC) is relatively safe for treatment of CVST, even in cases of hemorrhagic infarction, and is usually the first-line treatment. The usefulness of AC has already been well established.1-3 However, even with AC, symptoms continue to progress in a substantial number of patients. In Western From the *Departments of Neurology and Cerebrovascular Medicine; and †Endovascular Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan. Received October 7, 2011; revision received November 17, 2011; accepted November 18, 2011. Address correspondence to Ichiro Deguchi, MD, Saitama International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan. E-mail: ideguchi@saitama-med. ac.jp. 1052-3057/$ - see front matter Ó 2012 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2011.11.007
countries, neuroendovascular therapy (direct intrasinus thrombolysis and mechanical techniques) is now aggressively performed in such cases; in Japan, such case reports are rare.4,5 We report the case of a patient with CVST in whom, because of the deterioration of symptoms despite AC, urgent neuroendovascular intervention was required. The patient had a good outcome without any complications. Along with this case, the indications for endovascular therapy and some of the relevant literature are discussed.
Case Report A 63-year-old man with incoherent speech was admitted to the hospital. A CT scan of his head revealed hemorrhagic infarction of the left temporal lobe, and he was urgently admitted. His medical history was significant for dilated cardiomyopathy (DCM) and atrial fibrillation. Consciousness was impaired (Japanese Coma Scale I-3), and he had fluent spontaneous speech but with verbal paraphasia, jargon, and verbal preservation. There were no other neurologic abnormalities.
Journal of Stroke and Cerebrovascular Diseases, Vol. 21, No. 8 (November), 2012: pp 911.e5-911.e8
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Figure 1. Imaging findings of the head at time of arrival (A-D) and on day 3 (E-H). (A and B) On computed tomography, hemorrhagic infarction in the left temporal lobe and the cord-like high-density area of the left transverse sinus can be seen. (C) Acute hemorrhagic infarction of the left temporal lobe on diffusionweighted imaging. (D) Magnetic resonance angiography reveals occlusion of the right vertebral artery and fenestration in the left vertebral artery. (E and F) Newly appearing hemorrhagic infarction in the left cerebellum and thalamic infarction as seen on computed tomography. (G and H) Magnetic resonance venography reveals poorly depicted left sigmoid sinus–transverse sinus and straight sinus.
Laboratory findings included a normal blood count. Biochemistry tests revealed renal dysfunction and diabetes mellitus. D-dimer was 6.2 mg/mL (normal range ,1.0 mg/mL). Endocrine markers revealed elevated B-type natriuretic peptide (1207 pg/mL; normal range ,18.40 pg/mL). Plain chest radiography revealed cardiomegaly. On echocardiography, left ventricular wall motion was diffusely and severely decreased. Neuroradiologic findings included a CT scan of the head at the time of arrival to the hospital (Figs 1A and B) that revealed extensive hemorrhagic infarction in the left temporal lobe. There was a cord-like, high-density area corresponding to the left transverse sinus. A MRI scan of the head (Fig 1C) revealed hemorrhagic infarction in the left temporal lobe. Magnetic resonance angiography (MRA; Fig 1D) revealed occlusion of the right vertebral artery and fenestration in the left vertebral artery. Because hemorrhagic infarction was initially seen in the vascular territory of the left middle cerebral artery, cardioembolism was suspected. On day 1, edaravone and concentrated glycerin were started. However, on day 3, a CT scan of the head (Figs 1E and 1F) showed new left cerebellar and thalamic infarctions. Magnetic resonance venography (MRV; Figs 1G and 1H) showed poor depiction of veins from the straight sinus and left transverse sinus to the sigmoid sinus. CVST was diagnosed, and on the
same day, continuous infusion of unfractionated heparin (Novo Heparin; 12,000 units/day) was started. To achieve activated partial thromboplastin time from 1.5 to 2.0 times the baseline value, heparin was increased up to 15,000 units per day. On day 6, the patient’s level of consciousness suddenly deteriorated (Japanese Coma Scale III100). Urgent plain head CT revealed a new high-density area in the straight sinus. Blood tests found an abrupt increase in D-dimer (53.8 mg/mL). The sudden deterioration in consciousness was attributed to further thrombus progression in the deep cerebral venous system. This was resistant to AC, and urgent neuroendovascular intervention was performed. On a left internal carotid angiogram, the straight, left transverse, and sigmoid sinuses were occluded (Fig 2A). A 5F guiding catheter was passed from the left sigmoid sinus, through the transverse sinus, and from the confluence of the sinus to the straight sinus; then, after local injection of 60,000 units of urokinase (UK), the thrombus was aspirated. Subsequently, while moving the catheter tip in order through the confluence of the sinus, the transverse sinus, and the sigmoid sinus, a total of 300,000 units of UK was locally injected, and the thrombus was aspirated (Figs 2B and 2D). This resulted in complete recanalization of the straight sinus and partial recanalization of the transverse and sigmoid sinuses (Fig 2C). After treatment,
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Figure 2. Cerebral angiography (A- D) and head magnetic resonance venography (day after treatment; E). (A) Before treatment: Occlusion of the straight sinus and left sigmoid sinus–transverse sinus. (B) Under treatment: Local injection of UK and thrombus aspiration. (C) After treatment: Recanalization of the straight sinus and partial recanalization of the sigmoid sinus–transverse sinus. (D) Red thrombus. (E) Magnetic resonance venography: The straight sinus is depicted, but the left sigmoid sinus–transverse sinus is poorly depicted.
a CT scan of the head revealed no worsening of the hemorrhagic infarction or other hemorrhagic changes. On the day after neuroendovascular intervention, the patient’s consciousness improved to the same level as on hospital admission (Japanese Coma Scale I-3). MRV (Fig 2E) depicted the straight sinus, but the transverse and sigmoid sinuses were poorly depicted. Heparin infusion of 15,000 units per day was continued, and a repeat head CT scan confirmed no worsening of the hemorrhagic infarction. On day 11, oral warfarin was started. For heparin, a prothrombin time/international normalized ratio $2 was confirmed, and on day 17, it was discontinued. D-dimer decreased to 2.76 mg/mL. On day 44, the patient was transferred to a rehabilitation hospital with persistent aphasia and dysphagia. The modified Rankin Score after 90 days was 2.
Discussion In CVST, the safety and efficacy of AC have been shown, with good outcomes in many patients.6,7 However, there have also been cases in which symptoms progress and
outcomes are poor despite heparin treatment. With regard to factors leading to poor outcome despite heparin infusion, Mehraein et al8 reported a relationship with severely impaired consciousness, such as stupor or coma, mean age, and mean intracranial circulation time, while Ferro et al9 reported a particularly strong correlation was found between poor prognosis and coma (Glasgow Coma Scale ,9), thrombosis of the deep cerebral venous system, central nervous system infection, and cancer. The present patient was also initially treated with heparin infusion, but thrombosis progressed to the deep cerebral venous system and, with this, coma (Glasgow Coma Scale ,9) developed. In our patient, the outcome could have been poor with heparin alone. Stam et al10 conducted a prospective study in patients with severe CVST associated with the aforementioned risk factors who were treated with neuroendovascular therapy. They concluded that even in severe CVST, if large infarcts and herniation are absent, then thrombolytic therapy may be effective, although the risk of worsening cerebral hemorrhage remains. Similarly, in the present patient, risk factors for a poor outcome were coma, deep
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venous system thrombosis, but with endovascular therapy, the hemorrhagic infarction did not worsen, and a good outcome was achieved. In CVST, based on the American Heart Association/ American Stroke Association1 and the European Federation of Neurological Societies2 guidelines, endovascular treatment should be considered as 1 option in patients who, despite adequate AC, have worsening symptoms, do not have intracranial hemorrhage or impending herniation from a large hemorrhagic infarction, and have only a mild mass effect. In the Japanese Guidelines for the Management of Stroke,3 in severe cases or cases without improvement despite AC therapy, local fibrinolysis can be attempted. However, other neuroendovascular procedures are not mentioned. With neuroendovascular therapy in CVST, a high recanalization rate and good improvement of neurologic findings can be achieved, but complications such as intracranial hemorrhage have been reported.11-13 Currently, no randomized controlled trials of neuroendovascular therapy have been conducted, and efficacy and safety, including optimal substance, dosage, route (systemic or local), and method of administration (repeated bolus or bolus plus infusion) have not been established. However, in CVST—particularly deep CVST—severely impaired consciousness and poor outcomes often occur.14 Therefore, in patients with deep CVST, neuroendovascular therapy should be considered during the acute period, with careful attention to the timing of intervention.
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References 1. Saposnik G, Barinagarrementeria F, Brown RD Jr, et al. Diagnosis and management of cerebral venous thrombosis: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:1158-1192. 2. Einh€aupl K, Stam J, Bousser MG, et al. EFNS guideline on the treatment of cerebral venous and sinus
13.
14.
thrombosis in adult patients. Eur J Neurol 2010; 17:1229-1235. Shinohara Y, Ogawa A, Suzuki N, et al. Japanese Guidelines for the Management of Stroke—the joint committee on guideline for the management of stroke. Japanese Guidelines for the Management of Stroke 2009; 259-260. Uekusa H, Goto S, Noguchi Y, et al. A case of cerebral sinus thrombosis effectively treated with continuous intravenous local thrombolytic therapy [in Japanese]. NeurosurgEmerg 2006;11:192-199. Ida Y, Irie N, Furuichi S, et al. Recurrent cerebral venous sinus thrombosis in a patient with protein S deficiency [in Japanese]. Noushinkeigekasokuhou 2005;15:166-172. Einh€ aupl KM, Villringer A, Meister W, et al. Heparin treatment in sinus venous thrombosis. Lancet 1991; 338:597-600. de Bruijn SF, Stam J. Randomized, placebo-controlled trial of anticoagulant treatment with low-molecularweight heparin for cerebral sinus thrombosis. Stroke 1999;30:484-488. Mehraein S, Schmidtke K, Villringer A, et al. Heparin treatment in cerebral sinus and venous thrombosis: Patients at risk of fatal outcome. Cerebrovasc Dis 2003; 15:17-21. Ferro JM, Canh~ ao P, Stam J, et al. Prognosis of cerebral vein and dural sinus thrombosis: Results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004;35:664-670. Stam J, Majoie CB, van Delden OM, et al. Endovascular thrombectomy and thrombolysis for severe cerebral sinus thrombosis: A prospective study. Stroke 2008; 39:1487-1490. Horowitz M, Purdy P, Unwin H, et al. Treatment of dural sinus thrombosis using selective catheterization and urokinase. Ann Neurol 1995;38:58-67. Frey JL, Muro GJ, McDougall CG, et al. Cerebral venous thrombosis: combined intrathrombus rtPA and intravenous heparin. Stroke 1999;30:489-494. Kim SY, Suh JH. Direct endovascular thrombolytic therapy for dural sinus thrombosis: Infusion of alteplase. AJNR Am J Neuroradiol 1997;18:639-645. Haley EC Jr, Brashear HR, Barth JT, et al. Deep cerebral venous thrombosis. Clinical, neuroradiological, and neuropsychological correlates. Arch Neurol 1989;46: 337-340.
A Patient with Deep Cerebral Venous Sinus Thrombosis in whom Neuroendovascular Therapy was Effective Ichiro Deguchi, MD,* Tomohisa Dembo, MD,* Yuji Kato, MD,* Fumitaka Yamane, MD,† Shoichiro Ishihara, MD,† and Norio Tanahashi, MD*
A 63-year-old man presented with aphasia. A computed tomographic scan of the head revealed hemorrhagic infarction in the left temporal lobe. Magnetic resonance venography (MRV) revealed no flow from the straight sinus and left transverse sinus to the sigmoid sinus, indicating cerebral venous sinus thrombosis (CVST). Because of rapidly deteriorating consciousness despite heparin infusion, neuroendovascular therapy was performed, recanalization was achieved, and the level of consciousness improved. In Western countries, neuroendovascular therapy is often aggressively performed in patients with worsening symptoms despite anticoagulation. However, in Japan, such reports are extremely rare. We recommend neuroendovascular therapy for deep CVST resistant to anticoagulant therapy. Key Words: Deep cerebral venous sinus thrombosis—neuroendovascular therapy—resistant to anticoagulant therapy. Ó 2012 by National Stroke Association
Cerebral venous sinus thrombosis (CVST) accounts for 0.5% to 1.0% of all strokes,1 and with the introduction of computed tomographic (CT) and magnetic resonance imaging (MRI) scans and other advances in technology, a considerable number of cases are now being seen in clinical practice. Anticoagulation (AC) is relatively safe for treatment of CVST, even in cases of hemorrhagic infarction, and is usually the first-line treatment. The usefulness of AC has already been well established.1-3 However, even with AC, symptoms continue to progress in a substantial number of patients. In Western From the *Departments of Neurology and Cerebrovascular Medicine; and †Endovascular Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan. Received October 7, 2011; revision received November 17, 2011; accepted November 18, 2011. Address correspondence to Ichiro Deguchi, MD, Saitama International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan. E-mail: ideguchi@saitama-med. ac.jp. 1052-3057/$ - see front matter Ó 2012 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2011.11.007
countries, neuroendovascular therapy (direct intrasinus thrombolysis and mechanical techniques) is now aggressively performed in such cases; in Japan, such case reports are rare.4,5 We report the case of a patient with CVST in whom, because of the deterioration of symptoms despite AC, urgent neuroendovascular intervention was required. The patient had a good outcome without any complications. Along with this case, the indications for endovascular therapy and some of the relevant literature are discussed.
Case Report A 63-year-old man with incoherent speech was admitted to the hospital. A CT scan of his head revealed hemorrhagic infarction of the left temporal lobe, and he was urgently admitted. His medical history was significant for dilated cardiomyopathy (DCM) and atrial fibrillation. Consciousness was impaired (Japanese Coma Scale I-3), and he had fluent spontaneous speech but with verbal paraphasia, jargon, and verbal preservation. There were no other neurologic abnormalities.
Journal of Stroke and Cerebrovascular Diseases, Vol. 21, No. 8 (November), 2012: pp 911.e5-911.e8
911.e5
911.e6
I. DEGUCHI ET AL.
Figure 1. Imaging findings of the head at time of arrival (A-D) and on day 3 (E-H). (A and B) On computed tomography, hemorrhagic infarction in the left temporal lobe and the cord-like high-density area of the left transverse sinus can be seen. (C) Acute hemorrhagic infarction of the left temporal lobe on diffusionweighted imaging. (D) Magnetic resonance angiography reveals occlusion of the right vertebral artery and fenestration in the left vertebral artery. (E and F) Newly appearing hemorrhagic infarction in the left cerebellum and thalamic infarction as seen on computed tomography. (G and H) Magnetic resonance venography reveals poorly depicted left sigmoid sinus–transverse sinus and straight sinus.
Laboratory findings included a normal blood count. Biochemistry tests revealed renal dysfunction and diabetes mellitus. D-dimer was 6.2 mg/mL (normal range ,1.0 mg/mL). Endocrine markers revealed elevated B-type natriuretic peptide (1207 pg/mL; normal range ,18.40 pg/mL). Plain chest radiography revealed cardiomegaly. On echocardiography, left ventricular wall motion was diffusely and severely decreased. Neuroradiologic findings included a CT scan of the head at the time of arrival to the hospital (Figs 1A and B) that revealed extensive hemorrhagic infarction in the left temporal lobe. There was a cord-like, high-density area corresponding to the left transverse sinus. A MRI scan of the head (Fig 1C) revealed hemorrhagic infarction in the left temporal lobe. Magnetic resonance angiography (MRA; Fig 1D) revealed occlusion of the right vertebral artery and fenestration in the left vertebral artery. Because hemorrhagic infarction was initially seen in the vascular territory of the left middle cerebral artery, cardioembolism was suspected. On day 1, edaravone and concentrated glycerin were started. However, on day 3, a CT scan of the head (Figs 1E and 1F) showed new left cerebellar and thalamic infarctions. Magnetic resonance venography (MRV; Figs 1G and 1H) showed poor depiction of veins from the straight sinus and left transverse sinus to the sigmoid sinus. CVST was diagnosed, and on the
same day, continuous infusion of unfractionated heparin (Novo Heparin; 12,000 units/day) was started. To achieve activated partial thromboplastin time from 1.5 to 2.0 times the baseline value, heparin was increased up to 15,000 units per day. On day 6, the patient’s level of consciousness suddenly deteriorated (Japanese Coma Scale III100). Urgent plain head CT revealed a new high-density area in the straight sinus. Blood tests found an abrupt increase in D-dimer (53.8 mg/mL). The sudden deterioration in consciousness was attributed to further thrombus progression in the deep cerebral venous system. This was resistant to AC, and urgent neuroendovascular intervention was performed. On a left internal carotid angiogram, the straight, left transverse, and sigmoid sinuses were occluded (Fig 2A). A 5F guiding catheter was passed from the left sigmoid sinus, through the transverse sinus, and from the confluence of the sinus to the straight sinus; then, after local injection of 60,000 units of urokinase (UK), the thrombus was aspirated. Subsequently, while moving the catheter tip in order through the confluence of the sinus, the transverse sinus, and the sigmoid sinus, a total of 300,000 units of UK was locally injected, and the thrombus was aspirated (Figs 2B and 2D). This resulted in complete recanalization of the straight sinus and partial recanalization of the transverse and sigmoid sinuses (Fig 2C). After treatment,
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Figure 2. Cerebral angiography (A- D) and head magnetic resonance venography (day after treatment; E). (A) Before treatment: Occlusion of the straight sinus and left sigmoid sinus–transverse sinus. (B) Under treatment: Local injection of UK and thrombus aspiration. (C) After treatment: Recanalization of the straight sinus and partial recanalization of the sigmoid sinus–transverse sinus. (D) Red thrombus. (E) Magnetic resonance venography: The straight sinus is depicted, but the left sigmoid sinus–transverse sinus is poorly depicted.
a CT scan of the head revealed no worsening of the hemorrhagic infarction or other hemorrhagic changes. On the day after neuroendovascular intervention, the patient’s consciousness improved to the same level as on hospital admission (Japanese Coma Scale I-3). MRV (Fig 2E) depicted the straight sinus, but the transverse and sigmoid sinuses were poorly depicted. Heparin infusion of 15,000 units per day was continued, and a repeat head CT scan confirmed no worsening of the hemorrhagic infarction. On day 11, oral warfarin was started. For heparin, a prothrombin time/international normalized ratio $2 was confirmed, and on day 17, it was discontinued. D-dimer decreased to 2.76 mg/mL. On day 44, the patient was transferred to a rehabilitation hospital with persistent aphasia and dysphagia. The modified Rankin Score after 90 days was 2.
Discussion In CVST, the safety and efficacy of AC have been shown, with good outcomes in many patients.6,7 However, there have also been cases in which symptoms progress and
outcomes are poor despite heparin treatment. With regard to factors leading to poor outcome despite heparin infusion, Mehraein et al8 reported a relationship with severely impaired consciousness, such as stupor or coma, mean age, and mean intracranial circulation time, while Ferro et al9 reported a particularly strong correlation was found between poor prognosis and coma (Glasgow Coma Scale ,9), thrombosis of the deep cerebral venous system, central nervous system infection, and cancer. The present patient was also initially treated with heparin infusion, but thrombosis progressed to the deep cerebral venous system and, with this, coma (Glasgow Coma Scale ,9) developed. In our patient, the outcome could have been poor with heparin alone. Stam et al10 conducted a prospective study in patients with severe CVST associated with the aforementioned risk factors who were treated with neuroendovascular therapy. They concluded that even in severe CVST, if large infarcts and herniation are absent, then thrombolytic therapy may be effective, although the risk of worsening cerebral hemorrhage remains. Similarly, in the present patient, risk factors for a poor outcome were coma, deep
I. DEGUCHI ET AL.
911.e8
venous system thrombosis, but with endovascular therapy, the hemorrhagic infarction did not worsen, and a good outcome was achieved. In CVST, based on the American Heart Association/ American Stroke Association1 and the European Federation of Neurological Societies2 guidelines, endovascular treatment should be considered as 1 option in patients who, despite adequate AC, have worsening symptoms, do not have intracranial hemorrhage or impending herniation from a large hemorrhagic infarction, and have only a mild mass effect. In the Japanese Guidelines for the Management of Stroke,3 in severe cases or cases without improvement despite AC therapy, local fibrinolysis can be attempted. However, other neuroendovascular procedures are not mentioned. With neuroendovascular therapy in CVST, a high recanalization rate and good improvement of neurologic findings can be achieved, but complications such as intracranial hemorrhage have been reported.11-13 Currently, no randomized controlled trials of neuroendovascular therapy have been conducted, and efficacy and safety, including optimal substance, dosage, route (systemic or local), and method of administration (repeated bolus or bolus plus infusion) have not been established. However, in CVST—particularly deep CVST—severely impaired consciousness and poor outcomes often occur.14 Therefore, in patients with deep CVST, neuroendovascular therapy should be considered during the acute period, with careful attention to the timing of intervention.
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4.
5.
6.
7.
8.
9.
10.
11.
12.
References 1. Saposnik G, Barinagarrementeria F, Brown RD Jr, et al. Diagnosis and management of cerebral venous thrombosis: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:1158-1192. 2. Einh€aupl K, Stam J, Bousser MG, et al. EFNS guideline on the treatment of cerebral venous and sinus
13.
14.
thrombosis in adult patients. Eur J Neurol 2010; 17:1229-1235. Shinohara Y, Ogawa A, Suzuki N, et al. Japanese Guidelines for the Management of Stroke—the joint committee on guideline for the management of stroke. Japanese Guidelines for the Management of Stroke 2009; 259-260. Uekusa H, Goto S, Noguchi Y, et al. A case of cerebral sinus thrombosis effectively treated with continuous intravenous local thrombolytic therapy [in Japanese]. NeurosurgEmerg 2006;11:192-199. Ida Y, Irie N, Furuichi S, et al. Recurrent cerebral venous sinus thrombosis in a patient with protein S deficiency [in Japanese]. Noushinkeigekasokuhou 2005;15:166-172. Einh€ aupl KM, Villringer A, Meister W, et al. Heparin treatment in sinus venous thrombosis. Lancet 1991; 338:597-600. de Bruijn SF, Stam J. Randomized, placebo-controlled trial of anticoagulant treatment with low-molecularweight heparin for cerebral sinus thrombosis. Stroke 1999;30:484-488. Mehraein S, Schmidtke K, Villringer A, et al. Heparin treatment in cerebral sinus and venous thrombosis: Patients at risk of fatal outcome. Cerebrovasc Dis 2003; 15:17-21. Ferro JM, Canh~ ao P, Stam J, et al. Prognosis of cerebral vein and dural sinus thrombosis: Results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004;35:664-670. Stam J, Majoie CB, van Delden OM, et al. Endovascular thrombectomy and thrombolysis for severe cerebral sinus thrombosis: A prospective study. Stroke 2008; 39:1487-1490. Horowitz M, Purdy P, Unwin H, et al. Treatment of dural sinus thrombosis using selective catheterization and urokinase. Ann Neurol 1995;38:58-67. Frey JL, Muro GJ, McDougall CG, et al. Cerebral venous thrombosis: combined intrathrombus rtPA and intravenous heparin. Stroke 1999;30:489-494. Kim SY, Suh JH. Direct endovascular thrombolytic therapy for dural sinus thrombosis: Infusion of alteplase. AJNR Am J Neuroradiol 1997;18:639-645. Haley EC Jr, Brashear HR, Barth JT, et al. Deep cerebral venous thrombosis. Clinical, neuroradiological, and neuropsychological correlates. Arch Neurol 1989;46: 337-340.