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Geographically Remote Cerebral Venous Sinus Thrombosis in Patients with Intracranial Tumors
Original Article
Geographically Remote Cerebral Venous Sinus Thrombosis in Patients with Intracranial Tumors Daniel M.S. Raper1, Alicia M. Zukas2, David Schiff1,2, Ashok R. Asthagiri1
Cerebral venous sinus thrombosis (CVST) related to intracranial tumors has most commonly been recognized as an operative complication related to local operative factors such as retraction or direct venous injury. CVST may also be caused by tumor-related factors such as local mass effect but rarely occurs geographically remote from the site of the tumor. We report 6 cases treated at our institution of intracranial supratentorial tumors associated with CVST. In each case, the CVST was remote from the surgical site. In 3 cases CVST was noted at the time of resection, and 3 cases occurred in a delayed fashion. Each case is discussed in detail, and the utility of intraoperative magnetic resonance imaging in the early diagnosis of this complication is highlighted.
INTRODUCTION
C
erebral venous sinus thrombosis (CVST) is a rare, though recognized, complication of intracranial tumor resection and various chemotherapeutic agents. With modern imaging methods, including intraoperative magnetic resonance imaging (MRI), the ability to detect even small intracranial venous sinus filling defects has improved substantially. CVST can be a direct complication of tumor compression (or invasion) on a sinus, or from surgical manipulation requisite for adequate exposure (as in the case retrosigmoid approaches for vestibular schwannoma, or superior sagittal sinus exposure and retraction during interhemispheric approaches to the third ventricle).1 However, CVST that is remote from the site of the tumor has not been reported and remains a diagnostic and therapeutic
challenge. We report 6 cases of intracranial tumor associated with geographically remote CVST treated at our institution. These cases highlight the variety of circumstances in which intracranial tumors may be associated with CVST unrelated to surgical manipulation or local compression. METHODS We performed a retrospective review of selected patients presenting at our institution with intracranial tumors between March 2008 and November 2015. Patient and clinic records, as well as imaging reports, operative notes, and the Institutional Review Boardeapproved Neuro-Oncology patient database, were reviewed to identify patients who had a diagnosis of CVST and intracranial tumors. Patients with cerebellopontine angle tumors who developed CVST of the ipsilateral sigmoid sinus, those with parasagittal or parafalcine meningiomas who developed superior sagittal sinus thrombosis, or those in whom the CVST was judged to be a direct surgical complication, due to manipulation of a sinus or direct brain retraction, were not included. There were 6 documented cases of CVST remote from the site of the tumor. Inpatient and outpatient medical charts and imaging were reviewed for patient and tumor characteristics, pathologic details, intraoperative findings, complications, and outcomes (Table 1). The study was approved by the local institutional review board. Tumor Workup, Imaging, and Treatment Tumor workup included MRI, performed according to institutional protocol with precontrast and postcontrast 3D volumetric imaging. Intraoperative MRI was used in certain intracranial tumor resections performed after 2010. In cases of suspected or confirmed CVST, contrast-enhanced magnetic resonance venography was performed. Repeat imaging was performed at the treating neuro-oncologist’s discretion, usually at 3 and 6 months
Key words Cerebral venous sinus thrombosis - Glioblastoma - Intraoperative MRI - Neuro-oncology - Surgery
From the Departments of 1Neurosurgery and 2Neurology, Division of Neuro-Oncology, University of Virginia, Charlottesville, Virginia, USA
Abbreviations and Acronyms CVST: Cerebral venous sinus thrombosis DVT: Deep vein thrombosis MRI: Magnetic resonance imaging US: Ultrasound
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To whom correspondence should be addressed: Ashok R. Asthagiri [E-mail: [email protected]] Citation: World Neurosurg. (2017) 98:555-562. http://dx.doi.org/10.1016/j.wneu.2016.11.084
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Table 1. Patient, Tumor and Venous Sinus Thrombosis Characteristics Patient
Age
Sex
Tumor Location
Pathology Glioblastoma
CVST Location Left transverse, sigmoid
Treatment
1
21
F
Right frontal
Enoxaparin
2
61
M
Right frontal
Glioblastoma
Left transverse, sigmoid
Enoxaparin
3
32
M
Right lateral ventricle
Pilocytic astrocytoma
Bilateral transverse, sigmoid
Tinzaparin
4
75
M
Left frontal
Atypical meningioma (WHO II)
Left sigmoid
Warfarin
5
60
M
Left parietal
PCNSL
Right transverse, sigmoid, IJ
Dalteparin
6
21
M
Right frontal
Oligodendroglioma
Superior sagittal sinus
Fondaparinux
CVST, cerebral venous sinus thrombosis; F, female; M, male; WHO, World Health Organization; PCNSL, primary central nervous system lymphoma; IJ, internal jugular.
after discovery of the sinus thrombosis, unless clinical deterioration mandated earlier imaging. Each patient was managed with input from a multidisciplinary team. Advice on anticoagulation medication and duration was provided through consultation with the hematology service. In the case of Patient 2, the sinus thrombosis was felt to be most likely due to tumor-related factors and no systemic coagulopathy workup was performed. Otherwise, all patients underwent a coagulopathy workup including serotonin release assay for heparin-induced thrombocytopenia. The coagulopathy workup did not reveal systemic coagulopathy in any case in our series. Operative Details Stereotactic neuronavigation was used to plan a craniotomy over the tumor site in each case. The patients with frontal tumors were positioned supine, with the head turned away from the tumor, and a shoulder bump if necessary. Patient 5, who had a parietal lesion, was positioned supine, with head in neutral position and neck flexed, for the stereotactic biopsy. Patient 3, who had a lateral ventricular tumor, underwent an occipital approach and was positioned prone. Care was taken in each case to avoid compression of the contralateral internal and external jugular veins due to head turning. Fluid balance was maintained with infusion of crystalloid concomitant with intraoperative blood loss and urine output by the anesthesiology team. In no case was an internal or external jugular line placed perioperatively. RESULTS Case Series Patient 1. A 21-year-old right-handed female presented to the hospital with a week-long history of worsening headache, facial numbness, and diplopia. She had no prior medical history and was not taking the oral contraceptive pill. She was found to have a large, cystic right frontal tumor (Figure 1). Preoperative imaging did not reveal any evidence of intracranial venous thrombosis. She was taken for surgical resection of a glioblastoma with intraoperative MRI guidance. The bone flap was positioned laterally over the right frontal lobe, and the superior sagittal sinus was not exposed. Intraoperative MRI demonstrated evidence of left transverse sinus thrombosis, extending into the left sigmoid sinus and jugular bulb. She was started on prophylactic subcutaneous heparin on postoperative day 1 and
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on therapeutic anticoagulation with a heparin infusion on postoperative day 6. Deep vein thrombosis (DVT) ultrasound (US) performed at this time demonstrated no evidence of DVT. A full hypercoagulability workup, including antiphospholipid studies, was negative. A computed tomographic venogram (CTV) demonstrated improved filling of the left jugular bulb, and she was transitioned to therapeutic enoxaparin (1 mg/kg subcutaneous [SQ] twice daily) with a plan to continue for at least 3e6 months. Patient 2. A 61-year-old right-handed male with no prior thromboembolic history presented to the clinic with headache and progressive mental slowness. MRI demonstrated a large, right frontal, contrast-enhancing lesion, and he was recommended for surgical resection (Figure 2). Preoperative MRI with fiducial markers was performed the evening before surgery, and the patient was taken for a right frontal craniotomy and resection of a glioblastoma with intraoperative MRI guidance. Due to the large size and position in the medial portion of the frontal lobe, the anterior portion of the superior sagittal sinus was exposed during the surgical approach. Intraoperative imaging revealed left transverse and sigmoid sinus thrombosis, with extension into the left internal jugular vein, which was seen in retrospect on the preoperative imaging. The patient was started on subcutaneous heparin on postoperative day 1, which was switched to therapeutic heparin infusion on postoperative day 3. This was transitioned to warfarin after he became therapeutic. The patient was discharged after routine postoperative care, and a screening lower extremity US was negative for DVT. His warfarin was switched to enoxaparin due to difficulty controlling his international normalized ratio, and follow-up imaging 12 months postoperatively revealed a stable, chronic, nonocclusive thrombus in the left transverse and sigmoid sinuses. He continues on enoxaparin (1 mg/kg SQ twice daily) 14 months postoperatively. Patient 3. A 32-year-old right-handed male with no prior history of thromboembolism presented to an outside hospital with a severalweek history of headache, nausea, vomiting, and ataxia. He was found to have a contrast-enhancing tumor in the right lateral ventricle. He initially underwent a craniotomy and biopsy at another hospital, via a transcortical occipital approach, which was nondiagnostic. The biopsy was complicated by superior sagittal sinus and internal jugular vein thrombosis. Operative details and
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Figure 1. (A) 21-year-old female with a right frontal cystic glioblastoma. Preoperative imaging (B) reveals patency of bilateral transverse sinuses. Intraoperative magnetic resonance imaging (C, D) reveals left transverse and sigmoid sinus thrombosis (arrow). The patient was treated with therapeutic anticoagulation with enoxaparin. An interim computed tomography performed 2 weeks after initiation of anticoagulation (E) revealed hyperdensity in the left sigmoid sinus consistent with residual thrombus (black arrow).
positioning were not available for review from the outside institution. He was referred to our institution for further management. A repeat MRI demonstrated irregular bilateral transverse and sigmoid sinuses, with filling defects in bilateral internal jugular veins consistent with venous thromboses. The patient underwent a subtotal resection of a World Health Organization grade I pilocytic astrocytoma. The surgical approach was a re-do right occipital craniotomy, with the bone flap positioned superior to the transverse sinus and lateral to the superior sagittal sinus, neither of which were exposed during the surgery. His postoperative course was complicated by recurrent DVTs, although an extensive workup for primary hypercoagulable disorder was negative. At last follow-up, 2 years after his surgery, he continues on tinzaparin, a direct Xa inhibitor, due to refractory thromboses despite warfarin and low-molecular-weight heparin. Follow-up MRI demonstrated no residual transverse, sigmoid, or internal jugular vein thromboses.
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Patient 4. A 75-year-old right-handed male with no past medical history, including no prior history of DVT or pulmonary embolus, presented to the hospital with the acute onset of aphasia and was found to have a large left frontal tumor (Figure 3). At presentation, he was also found to be in atrial fibrillation with a rapid ventricular rate. He was started on antiepileptic medication with improvement in his aphasia and taken for surgical resection. He underwent a left frontal craniotomy, which did not extend to the superior sagittal sinus medially. A subtotal resection of a World Health Organization grade II atypical meningioma was performed, with the use of intraoperative MRI. Preoperative and immediate postoperative imaging revealed no evidence of CVST. The cardiology service recommended initiating warfarin therapy postoperatively for stroke prevention in the setting of newly diagnosed atrial fibrillation, and this was planned for 2 weeks after discharge. However, at his follow-up appointment he was noted to have a swollen calf and was found to have a right lower
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Figure 2. (A) 61-year-old male with a right frontal glioblastoma. Preoperative imaging (B) demonstrates left transverse and sigmoid sinus thrombosis (arrows). Intraoperative magnetic resonance imaging
extremity DVT and subacute bilateral pulmonary emboli without hemodynamic instability. A full hypercoagulable workup was negative. He was started on a course of fondaparinux (7.5 mg SQ daily), which was switched to warfarin and then discontinued after 3 months of treatment by the hematology team. On routine follow-
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(C) re-demonstrates the left transverse and sigmoid sinus thrombosis (arrows). Follow-up imaging 12 months postoperatively reveals the improved appearance of the sinus thrombosis.
up imaging at 6 months postoperatively, MRI demonstrated a new nonocclusive thrombus in the left sigmoid and distal transverse sinuses He restarted and continues on warfarin with duration of treatment to be guided by imaging evidence of resolution of this thrombus.
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ORIGINAL ARTICLE DANIEL M.S. RAPER ET AL.
Figure 3. (A, B) 75-year-old male with a 5 6 cm right frontal meningioma underwent subtotal surgical resection, followed by Gamma Knife radiosurgery. Immediate postoperative imaging (C) reveals patency
Patient 5. A 60-year-old right-handed male with a history of liver transplantation for nonalcoholic steatohepatitis, on chronic immunosuppressive therapy, but without prior thromboembolic history, presented with a seizure and was found to have a ringenhancing lesion in the left postcentral gyrus. He underwent biopsy of this lesion, which was consistent with a diffuse large B-cell primary central nervous system lymphoma. He underwent rituximab therapy and subsequently radiation therapy upon radiographic progression. He developed leg cramping and was found to have a left lower extremity DVT, which was treated with a 6-month course of dalteparin 10,000 units SQ daily and completely
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of the bilateral transverse and sigmoid sinuses (arrow). Routine postoperative imaging at 6 months (D) reveals nonocclusive thrombus in the left distal transverse and sigmoid sinuses.
resolved on follow-up lower extremity ultrasound. Twenty-eight months after surgery and 19 months after completion of radiation therapy, he presented to the hospital with a week-long history of headache, which had acutely worsened the day before presentation. He underwent MRI and magnetic resonance venography, which demonstrated acute thrombus in the right transverse and sigmoid sinuses, extending into the right internal jugular vein. The patient was started on intravenous heparin and transitioned to dalteparin (15,000 units subcutaneous daily). Subsequent imaging up to 5 months later demonstrated stable, chronic thrombus, and he was continued indefinitely on dalteparin 10,000 units daily.
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However, the patient experienced progressive contrast enhancement in bilateral periventricular regions, seizures, and progressive weakness and eventually expired 9 months after diagnosis of the sinus thrombosis. Patient 6. A 21-year-old right-handed male with no prior medical history presented with a seizure and was found to have a nonenhancing right frontal lobe intra-axial tumor. He underwent a right frontal craniotomy, which did not extend to the superior sagittal sinus, and resection of a grade II oligodendroglioma. This was observed for 56 months, until radiographic progression occurred, which was then treated with temozolomide for a further 38 months. Due to ongoing seizures and radiographic progression, he underwent a second right frontal craniotomy and resection, which revealed grade III oligodendroglioma. Again, the superior sagittal sinus was not exposed by the craniotomy. He underwent proton beam radiation with concurrent temozolomide for the following 4 months. Fifteen months later, he had clinical and radiographic progression and was treated with bevacizumab, panobinostat, and vorinostat. During an admission a month later, he had right leg pain and a lower extremity US demonstrated a chronic DVT. He was initially treated with heparin but developed thrombocytopenia. Although a workup for heparin-induced thrombocytopenia was negative, he was started on fondaparinux. A routine follow-up brain MRI performed 2 months later (18 months after his last surgery) demonstrated superior sagittal sinus thrombus and a related subacute right frontal intraparenchymal hemorrhage. In retrospect, the superior sagittal sinus thrombosis had been present at a scan 3 months earlier and likely antedated the initiation of anticoagulation for his DVT. He was maintained on fondaparinux (7.5 mg SQ daily). Three years later, he was taken for a stereotactic biopsy due to concern for radiographic progression, and anticoagulation was temporarily held perioperatively. Three months later, MRI showed a small right temporal hemorrhage, which resolved on subsequent CT. A repeat lower extremity DVT US was stable, and at this time his fondaparinux was stopped. DISCUSSION CVST is considered a relatively rare clinical entity, although the precise incidence is unknown. Due to the wide range of clinical
presentation and severity, diagnosis and initiation of necessary treatment may be delayed. CVST causes symptoms via venous hypertension and resultant cerebral edema and can cause a range of symptoms from headache to seizures and coma.2,3 Risk factors for CVST include prothrombotic conditions, pregnancy and oral contraceptive use, infection, surgical manipulation, and cancer.1,4,5 CVST has been associated with leukemias1,5-13 and other hematologic malignancies.6 CVST specifically associated with brain tumors has been rarely reported,14 even though DVT may be seen in up to 30% of patients with high-grade gliomas.7 A summary of these cases is shown in Table 2. There has been a case report of a patient with glioblastoma who developed CVST after radiotherapy, temozolomide, and bevacizumab therapy.17 A patient with a recurrent oligoastrocytoma developed fatal massive brain edema from widespread intraoperative sinus thrombosis.5 Two cases of CVST associated with leptomeningeal carcinomatosis secondary to lung adenocarcinoma, both occurring after radiation therapy, have been reported.5,9 CVST that is geographically remote from the site of the tumor itself has not been specifically addressed in the neurosurgical literature. We present a heterogeneous series of patients, which is a consequence of the rarity of this clinical entity. However, certain similarities and differences may be highlighted. Of the 6 patients in our series, 3 were discovered in a delayed fashion and 3 in the acute perioperative period, although one in this last category had preoperative CVST that was discovered at operation. Apart from headaches, which may be multifactorial, none of the patients in our series were symptomatic from their CVST. Furthermore, no patient was found to have a hypercoagulable disorder or other underlying systemic prothrombotic state. Among the patients developing delayed CVST, 1 was likely associated with new-onset atrial fibrillation, 1 with chemotherapy, and 1 possibly with radiation therapy. The heterogeneity of the presentation, timing, and response to therapy is dependent on individual patient history, intraoperative findings, severity of thrombosis, and response to initial anticoagulation therapy. CVST occurring remote from the surgical site, and in a delayed fashion after surgery (or biopsy, as in the case of Patient 5 in our series), is less likely to be directly related to surgical than patient- and tumor-related factors. Postoperative chemotherapy or
Table 2. Previously Reported Cases of Cerebral Venous Sinus Thrombosis Author & Year
Age Sex
Holzmann, 20155
Tumor Location
Pathology
CVST Location
29
F
Multiple metastases Lung Adenocarcinoma
NR
15
Redhu, 2013
62
F
Suprasellar
Meningioma
SSS, straight
Vargo, 201116
25
F
R temporal
Anaplastic astrocytoma SSS, bilateral transverse
Kozasa, 20136
55
M
R frontal lobe
Oligoastrocytoma
SSS, straight
64
F
Leptomeningeal carcinomatosis
Lung Adenocarcinoma
SSS, transverse, sigmoid
Oda, 2014
9
Time from Surgery
RT CT
14 months
Yes Yes Death 17 months after diagnosis
Outcome
Intraoperative No No Death postoperative day 2 7 weeks
Yes Yes Remains on LMWH 14 months postoperatively
Intraoperative No No Death NA
Yes Yes Stable 10 months after WBRT on warfarin
CVST, cerebral venous sinus thrombosis; RT, randomized trial; CT, controlled trial; F, female; NR, not reported; SSS, superior sagittal sinus; LMWH, low-molecular-weight heparin; M, male; WBRT, whole brain radiotherapy.
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REMOTE CVST IN PATIENTS WITH INTRACRANIAL TUMORS
radiation therapy, depending on the field and dosage, may be a predisposing factor to the development of CVST.5,16,18 This is a likely contributor to the development of CVST in Patient 6 in our series, as he developed this complication shortly after treatment with bevacizumab, panobinostat, and vorinostat. As further illustrated by Patient 6 in our series, the implication of CVST may significantly complicate the ongoing management of patients with supratentorial tumors. Guidelines for the diagnosis and management of CVST that recommend treatment with adjusted-dose unfractionated heparin or weight-based low-molecular-weight heparin as a first line (Class I; level of evidence B) have been published.19 This recommendation is based on 2 randomized, placebo-controlled trials supporting the use of heparin for CVST.20,21 For brain tumor patients, the need for anticoagulation must be balanced with often multiple intracranial procedures, as well as the risk of hemorrhage from medications such as bevacizumab. Close collaboration with a hematologist experienced in the management of these complex patients is essential. When seen perioperatively, venous sinus thrombosis is more commonly a direct consequence of surgical manipulation or the surgical approach. When parasagittal or falcine meningiomas cause mass effect on the superior sagittal sinus or invade it directly, the sinus may become occluded. When this is a consequence of tumor infiltration and/or compression, the pathogenesis is usually prolonged over a number of years and the occlusion may be asymptomatic. However, if it is a consequence of surgical manipulation, an acute and symptomatic sinus thrombosis may result.17 CVST may also be associated with the placement of central venous catheters, although not applicable in any cases in this series. Venous sinus thrombosis has been associated with the retrosigmoid approach for cerebellopontine angle tumors.4 Exposed dural sinus wall, in combination with heat from the surgical drill, over an extended period, is the most common cause of sinus thrombosis. In addition, the emissary vein, which drains into the sigmoid sinus, is encountered in the surgical approach and occlusion with prothrombotic material such as FloSeal (Baxter, Deerfield, Illinois, USA) may result in sinus thrombosis. Our current series highlights the utility of intraoperative MRI, which in 1 case provided a diagnosis of early CVST (Patient 2) and in another confirmed a previously missed preoperative finding (Patient 4). Although it is a rare occurrence, close attention should
REFERENCES 1. Beslow LA, Abend NS, Smith SE. Cerebral sinus venous thrombosis complicated by cerebellar hemorrhage in a child with acute promyelocytic leukemia. J Child Neurol. 2009;24:110-114. 2. Coutinho JM, Stam J, Canhão P, Barinagarrementeria F, Bousser MG, Ferro JM, et al. Cerebral venous thrombosis in the absence of headache. Stroke. 2015;46:245-247. 3. Thorell SE, Parry-Jones AR, Punter M, Hurford R, Thachil J. Cerebral venous thrombosis—a primer for the haematologist. Blood Rev. 2015;29:45-50. 4. Hannawi Y, Bershad E, Suarez J, Shaltoni H, Yoshor D, Venkatasubba Rao C. Post surgical
be paid to intraoperative images including postcontrast imaging through the sigmoid sinuses. It is our practice to discuss the findings of the intraoperative MRI with an attending neuroradiologist before closure for all cases involving this imaging modality. The management of early postoperative CVST is complicated by the risk of postoperative hemorrhage and wound healing issues. Though no evidence-based guidelines exist, treatment of CVST with full-dose anticoagulation appears to reduce the incidence of death and severe morbidity.22,23 A recent small series of lateral sinus thromboses after posterior fossa surgery, treated with anticoagulation, did not observe increased incidence of intracranial hemorrhage.24 Our anecdotal experience has been to proceed with therapeutic anticoagulation by postoperative day 3 or earlier depending on the severity of the thrombosis and the presumed risk of postoperative bleeding, but an individualized treatment decision must be made, carefully weighing risks and benefits of early postoperative anticoagulation. Luckily no patient in our series experienced symptoms related to their sinus thrombosis. In asymptomatic cases, although we err on the side of formal anticoagulation, the ideal treatment algorithm has not been evaluated. Close collaboration with hematology colleagues is necessary to weigh the risks and benefits in each individual case. CONCLUSIONS Cerebral venous sinus thrombosis may be associated with intracranial tumors in either the acute or late postoperative periods. Intraoperative MRI offers a useful tool to diagnose early CVST, which has important consequences for early postoperative anticoagulation treatment planning. Although rare, CVST may occur remotely from the site of low- and high-grade intracranial tumors, indicating that even benign intracranial neoplasms may induce a systemic prothrombotic state. However, the true incidence of this phenomenon remains unclear, and a prospective study to assess this issue may be warranted. While it is clear that CVST can cause significant morbidity, the clinical significance of asymptomatic imaging findings and necessity of treatment remain topics of debate. Guidelines have not been formulated for the ideal treatment in these asymptomatic cases, but close collaboration with a hematologist is recommended to fully consider the risks and benefits of therapeutic anticoagulation.
cerebral venous sinus thrombosis: a rare surgical complication and challenging management case (abstract). Neurology. 2012;78. P06.260. 5. Holzmann K, Kropfmüller R, Schinko H, Bogner S, Fellner F, Arzt W, et al. Lung cancer in pregnancy. Wien Klin Wochenschr. 2015;127:639-644. 6. Kozasa Y, Takaseya H, Koga Y, Hiraki T, Mishima Y, Niiyama S, et al. A case of delayed emergence from anesthesia caused by postoperative brain edema associated with unexpected cerebral venous sinus thrombosis. J Anesth. 2013; 27:764-767. 7. Li HK, Harding V, Williamson R, Blagden S, Gabra H, Agarwal R. Cerebral sinus thrombosis
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and leptomeningeal carcinomatosis in a patient with ovarian cancer. J Clin Oncol. 2012;30:e19-e20. 8. Mazzoleni S, Putti MC, Simioni P, Sainati L, Tormene D, Manara R, et al. Early cerebral sinovenous thrombosis in a child with acute lymphoblastic leukemia carrying the prothrombin G20210A variant: a case report and review of the literature. Blood Coagul Fibrinolysis. 2005;16: 43-49. 9. Oda N, Sakugawa M, Bessho A, Horiuchi T, Hosokawa S, Toyota Y, et al. Cerebral venous sinus thrombosis concomitant with leptomeningeal carcinomatosis, in a patient with epidermal growth factor receptor-mutated lung cancer. Oncol Lett. 2014;8:2489-2492.
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10. Raizer JJ, DeAngelis LM. Cerebral sinus thrombosis diagnosed by MRI and MR venography in cancer patients. Neurology. 2000;54: 1222-1226. 11. Ranta S, Tuckuviene R, Mäkipernaa A, Albertsen BK, Frisk T, Tedgård U, et al. Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia—a multicentre study from the Nordic Society of Paediatric Haematology and Oncology. Br J Haematol. 2015;168: 547-552.
REMOTE CVST IN PATIENTS WITH INTRACRANIAL TUMORS
16. Vargo JA, Snelling BM, Ghareeb ER, John K, Frame JN, Schmidt JH, et al. Dural venous sinus thrombosis in anaplastic astrocytoma following concurrent temozolomide and focal brain radiotherapy plus bevacizumab. J Neurooncol. 2011;104: 595-598. 17. Raza SM, Gallia GL, Brem H, Weingart JD, Long DM, Olivi A. Perioperative and long-term outcomes from the management of parasagittal meningiomas invading the superior sagittal sinus. Neurosurgery. 2010;67:885.
12. Song L, Lu H, Chang C, Li X, Zhang Z. Cerebral venous and sinus thrombosis in a patient with acute promyelocytic leukemia during all-trans retinoic acid induction treatment. Blood Coagul Fibrinolysis. 2014;25:773-776.
18. Lee KR, Subrayan V, Win MM, Fadhilah Mohamad N, Patel D. ATRA-induced cerebral sinus thrombosis. J Thromb Thrombolysis. 2014;38: 87-89.
13. Wang TY, Yen HJ, Hung GY, Hsieh MY, Tang RB. A rare complication in a child undergoing chemotherapy for acute lymphoblastic leukemia: superior sagittal sinus thrombosis. J Chin Med Assoc. 2011;74:183-187.
19. Saposnik G, Barinagarrementeria F, Brown RD, Bushnell CD, Cucchiara B, Cushman M, 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.
14. Pan E, Tsai JS, Mitchell SB. Retrospective study of venous thromboembolic and intracerebral hemorrhagic events in glioblastoma patients. Anticancer Res. 2009;29:4309-4313. 15. Redhu S, Mohd Abdul M, Pandey P, Devaragudi TS. Distant cerebral venous sinus thrombosis in meningioma surgery: a rare complication. Neurol India. 2013;61:180-181.
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low-molecular-weight heparin for cerebral sinus thrombosis. Stroke. 1999;30:484-488. 22. Coutinho JM, de Bruijn SF, deVeber G, Stam J. Anticoagulation for cerebral venous sinus thrombosis. Stroke. 2012;43:e41-e42. 23. Coutinho JM, Seelig R, Bousser MG, Canhao P, Ferro JM, Stam J. Treatment variations in cerebral venous thrombosis: an international survey. Cerebrovasc Dis. 2011;32:298-300. 24. Apra C, Kotbi O, Turc G, Corns R, Pages M, Souillard-Scemama R, et al. Presentation and management of lateral sinus thrombosis following posterior fossa surgery [e-pub ahead of print]. J Neurosurg. 2016:1-9; http://dx.doi.org/ 10.3171/2015.11.JNS151881.
Conflict of interest statement: The authors report no conflict of interest exists concerning the materials or methods used in this study or the findings specified in this paper. Received 23 September 2016; accepted 15 November 2016
20. Einhaupl KM, Villringer A, Meister W, Mehraein S, Garner C, Pellkofer M, et al. Heparin treatment in sinus venous thrombosis. Lancet. 1991;338:597-600.
Citation: World Neurosurg. (2017) 98:555-562. http://dx.doi.org/10.1016/j.wneu.2016.11.084
21. de Bruijn SF, Stam J. Randomized, placebocontrolled trial of anticoagulant treatment with
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Geographically Remote Cerebral Venous Sinus Thrombosis in Patients with Intracranial Tumors Daniel M.S. Raper1, Alicia M. Zukas2, David Schiff1,2, Ashok R. Asthagiri1
Cerebral venous sinus thrombosis (CVST) related to intracranial tumors has most commonly been recognized as an operative complication related to local operative factors such as retraction or direct venous injury. CVST may also be caused by tumor-related factors such as local mass effect but rarely occurs geographically remote from the site of the tumor. We report 6 cases treated at our institution of intracranial supratentorial tumors associated with CVST. In each case, the CVST was remote from the surgical site. In 3 cases CVST was noted at the time of resection, and 3 cases occurred in a delayed fashion. Each case is discussed in detail, and the utility of intraoperative magnetic resonance imaging in the early diagnosis of this complication is highlighted.
INTRODUCTION
C
erebral venous sinus thrombosis (CVST) is a rare, though recognized, complication of intracranial tumor resection and various chemotherapeutic agents. With modern imaging methods, including intraoperative magnetic resonance imaging (MRI), the ability to detect even small intracranial venous sinus filling defects has improved substantially. CVST can be a direct complication of tumor compression (or invasion) on a sinus, or from surgical manipulation requisite for adequate exposure (as in the case retrosigmoid approaches for vestibular schwannoma, or superior sagittal sinus exposure and retraction during interhemispheric approaches to the third ventricle).1 However, CVST that is remote from the site of the tumor has not been reported and remains a diagnostic and therapeutic
challenge. We report 6 cases of intracranial tumor associated with geographically remote CVST treated at our institution. These cases highlight the variety of circumstances in which intracranial tumors may be associated with CVST unrelated to surgical manipulation or local compression. METHODS We performed a retrospective review of selected patients presenting at our institution with intracranial tumors between March 2008 and November 2015. Patient and clinic records, as well as imaging reports, operative notes, and the Institutional Review Boardeapproved Neuro-Oncology patient database, were reviewed to identify patients who had a diagnosis of CVST and intracranial tumors. Patients with cerebellopontine angle tumors who developed CVST of the ipsilateral sigmoid sinus, those with parasagittal or parafalcine meningiomas who developed superior sagittal sinus thrombosis, or those in whom the CVST was judged to be a direct surgical complication, due to manipulation of a sinus or direct brain retraction, were not included. There were 6 documented cases of CVST remote from the site of the tumor. Inpatient and outpatient medical charts and imaging were reviewed for patient and tumor characteristics, pathologic details, intraoperative findings, complications, and outcomes (Table 1). The study was approved by the local institutional review board. Tumor Workup, Imaging, and Treatment Tumor workup included MRI, performed according to institutional protocol with precontrast and postcontrast 3D volumetric imaging. Intraoperative MRI was used in certain intracranial tumor resections performed after 2010. In cases of suspected or confirmed CVST, contrast-enhanced magnetic resonance venography was performed. Repeat imaging was performed at the treating neuro-oncologist’s discretion, usually at 3 and 6 months
Key words Cerebral venous sinus thrombosis - Glioblastoma - Intraoperative MRI - Neuro-oncology - Surgery
From the Departments of 1Neurosurgery and 2Neurology, Division of Neuro-Oncology, University of Virginia, Charlottesville, Virginia, USA
Abbreviations and Acronyms CVST: Cerebral venous sinus thrombosis DVT: Deep vein thrombosis MRI: Magnetic resonance imaging US: Ultrasound
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To whom correspondence should be addressed: Ashok R. Asthagiri [E-mail: [email protected]] Citation: World Neurosurg. (2017) 98:555-562. http://dx.doi.org/10.1016/j.wneu.2016.11.084
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Table 1. Patient, Tumor and Venous Sinus Thrombosis Characteristics Patient
Age
Sex
Tumor Location
Pathology Glioblastoma
CVST Location Left transverse, sigmoid
Treatment
1
21
F
Right frontal
Enoxaparin
2
61
M
Right frontal
Glioblastoma
Left transverse, sigmoid
Enoxaparin
3
32
M
Right lateral ventricle
Pilocytic astrocytoma
Bilateral transverse, sigmoid
Tinzaparin
4
75
M
Left frontal
Atypical meningioma (WHO II)
Left sigmoid
Warfarin
5
60
M
Left parietal
PCNSL
Right transverse, sigmoid, IJ
Dalteparin
6
21
M
Right frontal
Oligodendroglioma
Superior sagittal sinus
Fondaparinux
CVST, cerebral venous sinus thrombosis; F, female; M, male; WHO, World Health Organization; PCNSL, primary central nervous system lymphoma; IJ, internal jugular.
after discovery of the sinus thrombosis, unless clinical deterioration mandated earlier imaging. Each patient was managed with input from a multidisciplinary team. Advice on anticoagulation medication and duration was provided through consultation with the hematology service. In the case of Patient 2, the sinus thrombosis was felt to be most likely due to tumor-related factors and no systemic coagulopathy workup was performed. Otherwise, all patients underwent a coagulopathy workup including serotonin release assay for heparin-induced thrombocytopenia. The coagulopathy workup did not reveal systemic coagulopathy in any case in our series. Operative Details Stereotactic neuronavigation was used to plan a craniotomy over the tumor site in each case. The patients with frontal tumors were positioned supine, with the head turned away from the tumor, and a shoulder bump if necessary. Patient 5, who had a parietal lesion, was positioned supine, with head in neutral position and neck flexed, for the stereotactic biopsy. Patient 3, who had a lateral ventricular tumor, underwent an occipital approach and was positioned prone. Care was taken in each case to avoid compression of the contralateral internal and external jugular veins due to head turning. Fluid balance was maintained with infusion of crystalloid concomitant with intraoperative blood loss and urine output by the anesthesiology team. In no case was an internal or external jugular line placed perioperatively. RESULTS Case Series Patient 1. A 21-year-old right-handed female presented to the hospital with a week-long history of worsening headache, facial numbness, and diplopia. She had no prior medical history and was not taking the oral contraceptive pill. She was found to have a large, cystic right frontal tumor (Figure 1). Preoperative imaging did not reveal any evidence of intracranial venous thrombosis. She was taken for surgical resection of a glioblastoma with intraoperative MRI guidance. The bone flap was positioned laterally over the right frontal lobe, and the superior sagittal sinus was not exposed. Intraoperative MRI demonstrated evidence of left transverse sinus thrombosis, extending into the left sigmoid sinus and jugular bulb. She was started on prophylactic subcutaneous heparin on postoperative day 1 and
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on therapeutic anticoagulation with a heparin infusion on postoperative day 6. Deep vein thrombosis (DVT) ultrasound (US) performed at this time demonstrated no evidence of DVT. A full hypercoagulability workup, including antiphospholipid studies, was negative. A computed tomographic venogram (CTV) demonstrated improved filling of the left jugular bulb, and she was transitioned to therapeutic enoxaparin (1 mg/kg subcutaneous [SQ] twice daily) with a plan to continue for at least 3e6 months. Patient 2. A 61-year-old right-handed male with no prior thromboembolic history presented to the clinic with headache and progressive mental slowness. MRI demonstrated a large, right frontal, contrast-enhancing lesion, and he was recommended for surgical resection (Figure 2). Preoperative MRI with fiducial markers was performed the evening before surgery, and the patient was taken for a right frontal craniotomy and resection of a glioblastoma with intraoperative MRI guidance. Due to the large size and position in the medial portion of the frontal lobe, the anterior portion of the superior sagittal sinus was exposed during the surgical approach. Intraoperative imaging revealed left transverse and sigmoid sinus thrombosis, with extension into the left internal jugular vein, which was seen in retrospect on the preoperative imaging. The patient was started on subcutaneous heparin on postoperative day 1, which was switched to therapeutic heparin infusion on postoperative day 3. This was transitioned to warfarin after he became therapeutic. The patient was discharged after routine postoperative care, and a screening lower extremity US was negative for DVT. His warfarin was switched to enoxaparin due to difficulty controlling his international normalized ratio, and follow-up imaging 12 months postoperatively revealed a stable, chronic, nonocclusive thrombus in the left transverse and sigmoid sinuses. He continues on enoxaparin (1 mg/kg SQ twice daily) 14 months postoperatively. Patient 3. A 32-year-old right-handed male with no prior history of thromboembolism presented to an outside hospital with a severalweek history of headache, nausea, vomiting, and ataxia. He was found to have a contrast-enhancing tumor in the right lateral ventricle. He initially underwent a craniotomy and biopsy at another hospital, via a transcortical occipital approach, which was nondiagnostic. The biopsy was complicated by superior sagittal sinus and internal jugular vein thrombosis. Operative details and
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Figure 1. (A) 21-year-old female with a right frontal cystic glioblastoma. Preoperative imaging (B) reveals patency of bilateral transverse sinuses. Intraoperative magnetic resonance imaging (C, D) reveals left transverse and sigmoid sinus thrombosis (arrow). The patient was treated with therapeutic anticoagulation with enoxaparin. An interim computed tomography performed 2 weeks after initiation of anticoagulation (E) revealed hyperdensity in the left sigmoid sinus consistent with residual thrombus (black arrow).
positioning were not available for review from the outside institution. He was referred to our institution for further management. A repeat MRI demonstrated irregular bilateral transverse and sigmoid sinuses, with filling defects in bilateral internal jugular veins consistent with venous thromboses. The patient underwent a subtotal resection of a World Health Organization grade I pilocytic astrocytoma. The surgical approach was a re-do right occipital craniotomy, with the bone flap positioned superior to the transverse sinus and lateral to the superior sagittal sinus, neither of which were exposed during the surgery. His postoperative course was complicated by recurrent DVTs, although an extensive workup for primary hypercoagulable disorder was negative. At last follow-up, 2 years after his surgery, he continues on tinzaparin, a direct Xa inhibitor, due to refractory thromboses despite warfarin and low-molecular-weight heparin. Follow-up MRI demonstrated no residual transverse, sigmoid, or internal jugular vein thromboses.
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Patient 4. A 75-year-old right-handed male with no past medical history, including no prior history of DVT or pulmonary embolus, presented to the hospital with the acute onset of aphasia and was found to have a large left frontal tumor (Figure 3). At presentation, he was also found to be in atrial fibrillation with a rapid ventricular rate. He was started on antiepileptic medication with improvement in his aphasia and taken for surgical resection. He underwent a left frontal craniotomy, which did not extend to the superior sagittal sinus medially. A subtotal resection of a World Health Organization grade II atypical meningioma was performed, with the use of intraoperative MRI. Preoperative and immediate postoperative imaging revealed no evidence of CVST. The cardiology service recommended initiating warfarin therapy postoperatively for stroke prevention in the setting of newly diagnosed atrial fibrillation, and this was planned for 2 weeks after discharge. However, at his follow-up appointment he was noted to have a swollen calf and was found to have a right lower
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Figure 2. (A) 61-year-old male with a right frontal glioblastoma. Preoperative imaging (B) demonstrates left transverse and sigmoid sinus thrombosis (arrows). Intraoperative magnetic resonance imaging
extremity DVT and subacute bilateral pulmonary emboli without hemodynamic instability. A full hypercoagulable workup was negative. He was started on a course of fondaparinux (7.5 mg SQ daily), which was switched to warfarin and then discontinued after 3 months of treatment by the hematology team. On routine follow-
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(C) re-demonstrates the left transverse and sigmoid sinus thrombosis (arrows). Follow-up imaging 12 months postoperatively reveals the improved appearance of the sinus thrombosis.
up imaging at 6 months postoperatively, MRI demonstrated a new nonocclusive thrombus in the left sigmoid and distal transverse sinuses He restarted and continues on warfarin with duration of treatment to be guided by imaging evidence of resolution of this thrombus.
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Figure 3. (A, B) 75-year-old male with a 5 6 cm right frontal meningioma underwent subtotal surgical resection, followed by Gamma Knife radiosurgery. Immediate postoperative imaging (C) reveals patency
Patient 5. A 60-year-old right-handed male with a history of liver transplantation for nonalcoholic steatohepatitis, on chronic immunosuppressive therapy, but without prior thromboembolic history, presented with a seizure and was found to have a ringenhancing lesion in the left postcentral gyrus. He underwent biopsy of this lesion, which was consistent with a diffuse large B-cell primary central nervous system lymphoma. He underwent rituximab therapy and subsequently radiation therapy upon radiographic progression. He developed leg cramping and was found to have a left lower extremity DVT, which was treated with a 6-month course of dalteparin 10,000 units SQ daily and completely
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of the bilateral transverse and sigmoid sinuses (arrow). Routine postoperative imaging at 6 months (D) reveals nonocclusive thrombus in the left distal transverse and sigmoid sinuses.
resolved on follow-up lower extremity ultrasound. Twenty-eight months after surgery and 19 months after completion of radiation therapy, he presented to the hospital with a week-long history of headache, which had acutely worsened the day before presentation. He underwent MRI and magnetic resonance venography, which demonstrated acute thrombus in the right transverse and sigmoid sinuses, extending into the right internal jugular vein. The patient was started on intravenous heparin and transitioned to dalteparin (15,000 units subcutaneous daily). Subsequent imaging up to 5 months later demonstrated stable, chronic thrombus, and he was continued indefinitely on dalteparin 10,000 units daily.
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However, the patient experienced progressive contrast enhancement in bilateral periventricular regions, seizures, and progressive weakness and eventually expired 9 months after diagnosis of the sinus thrombosis. Patient 6. A 21-year-old right-handed male with no prior medical history presented with a seizure and was found to have a nonenhancing right frontal lobe intra-axial tumor. He underwent a right frontal craniotomy, which did not extend to the superior sagittal sinus, and resection of a grade II oligodendroglioma. This was observed for 56 months, until radiographic progression occurred, which was then treated with temozolomide for a further 38 months. Due to ongoing seizures and radiographic progression, he underwent a second right frontal craniotomy and resection, which revealed grade III oligodendroglioma. Again, the superior sagittal sinus was not exposed by the craniotomy. He underwent proton beam radiation with concurrent temozolomide for the following 4 months. Fifteen months later, he had clinical and radiographic progression and was treated with bevacizumab, panobinostat, and vorinostat. During an admission a month later, he had right leg pain and a lower extremity US demonstrated a chronic DVT. He was initially treated with heparin but developed thrombocytopenia. Although a workup for heparin-induced thrombocytopenia was negative, he was started on fondaparinux. A routine follow-up brain MRI performed 2 months later (18 months after his last surgery) demonstrated superior sagittal sinus thrombus and a related subacute right frontal intraparenchymal hemorrhage. In retrospect, the superior sagittal sinus thrombosis had been present at a scan 3 months earlier and likely antedated the initiation of anticoagulation for his DVT. He was maintained on fondaparinux (7.5 mg SQ daily). Three years later, he was taken for a stereotactic biopsy due to concern for radiographic progression, and anticoagulation was temporarily held perioperatively. Three months later, MRI showed a small right temporal hemorrhage, which resolved on subsequent CT. A repeat lower extremity DVT US was stable, and at this time his fondaparinux was stopped. DISCUSSION CVST is considered a relatively rare clinical entity, although the precise incidence is unknown. Due to the wide range of clinical
presentation and severity, diagnosis and initiation of necessary treatment may be delayed. CVST causes symptoms via venous hypertension and resultant cerebral edema and can cause a range of symptoms from headache to seizures and coma.2,3 Risk factors for CVST include prothrombotic conditions, pregnancy and oral contraceptive use, infection, surgical manipulation, and cancer.1,4,5 CVST has been associated with leukemias1,5-13 and other hematologic malignancies.6 CVST specifically associated with brain tumors has been rarely reported,14 even though DVT may be seen in up to 30% of patients with high-grade gliomas.7 A summary of these cases is shown in Table 2. There has been a case report of a patient with glioblastoma who developed CVST after radiotherapy, temozolomide, and bevacizumab therapy.17 A patient with a recurrent oligoastrocytoma developed fatal massive brain edema from widespread intraoperative sinus thrombosis.5 Two cases of CVST associated with leptomeningeal carcinomatosis secondary to lung adenocarcinoma, both occurring after radiation therapy, have been reported.5,9 CVST that is geographically remote from the site of the tumor itself has not been specifically addressed in the neurosurgical literature. We present a heterogeneous series of patients, which is a consequence of the rarity of this clinical entity. However, certain similarities and differences may be highlighted. Of the 6 patients in our series, 3 were discovered in a delayed fashion and 3 in the acute perioperative period, although one in this last category had preoperative CVST that was discovered at operation. Apart from headaches, which may be multifactorial, none of the patients in our series were symptomatic from their CVST. Furthermore, no patient was found to have a hypercoagulable disorder or other underlying systemic prothrombotic state. Among the patients developing delayed CVST, 1 was likely associated with new-onset atrial fibrillation, 1 with chemotherapy, and 1 possibly with radiation therapy. The heterogeneity of the presentation, timing, and response to therapy is dependent on individual patient history, intraoperative findings, severity of thrombosis, and response to initial anticoagulation therapy. CVST occurring remote from the surgical site, and in a delayed fashion after surgery (or biopsy, as in the case of Patient 5 in our series), is less likely to be directly related to surgical than patient- and tumor-related factors. Postoperative chemotherapy or
Table 2. Previously Reported Cases of Cerebral Venous Sinus Thrombosis Author & Year
Age Sex
Holzmann, 20155
Tumor Location
Pathology
CVST Location
29
F
Multiple metastases Lung Adenocarcinoma
NR
15
Redhu, 2013
62
F
Suprasellar
Meningioma
SSS, straight
Vargo, 201116
25
F
R temporal
Anaplastic astrocytoma SSS, bilateral transverse
Kozasa, 20136
55
M
R frontal lobe
Oligoastrocytoma
SSS, straight
64
F
Leptomeningeal carcinomatosis
Lung Adenocarcinoma
SSS, transverse, sigmoid
Oda, 2014
9
Time from Surgery
RT CT
14 months
Yes Yes Death 17 months after diagnosis
Outcome
Intraoperative No No Death postoperative day 2 7 weeks
Yes Yes Remains on LMWH 14 months postoperatively
Intraoperative No No Death NA
Yes Yes Stable 10 months after WBRT on warfarin
CVST, cerebral venous sinus thrombosis; RT, randomized trial; CT, controlled trial; F, female; NR, not reported; SSS, superior sagittal sinus; LMWH, low-molecular-weight heparin; M, male; WBRT, whole brain radiotherapy.
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radiation therapy, depending on the field and dosage, may be a predisposing factor to the development of CVST.5,16,18 This is a likely contributor to the development of CVST in Patient 6 in our series, as he developed this complication shortly after treatment with bevacizumab, panobinostat, and vorinostat. As further illustrated by Patient 6 in our series, the implication of CVST may significantly complicate the ongoing management of patients with supratentorial tumors. Guidelines for the diagnosis and management of CVST that recommend treatment with adjusted-dose unfractionated heparin or weight-based low-molecular-weight heparin as a first line (Class I; level of evidence B) have been published.19 This recommendation is based on 2 randomized, placebo-controlled trials supporting the use of heparin for CVST.20,21 For brain tumor patients, the need for anticoagulation must be balanced with often multiple intracranial procedures, as well as the risk of hemorrhage from medications such as bevacizumab. Close collaboration with a hematologist experienced in the management of these complex patients is essential. When seen perioperatively, venous sinus thrombosis is more commonly a direct consequence of surgical manipulation or the surgical approach. When parasagittal or falcine meningiomas cause mass effect on the superior sagittal sinus or invade it directly, the sinus may become occluded. When this is a consequence of tumor infiltration and/or compression, the pathogenesis is usually prolonged over a number of years and the occlusion may be asymptomatic. However, if it is a consequence of surgical manipulation, an acute and symptomatic sinus thrombosis may result.17 CVST may also be associated with the placement of central venous catheters, although not applicable in any cases in this series. Venous sinus thrombosis has been associated with the retrosigmoid approach for cerebellopontine angle tumors.4 Exposed dural sinus wall, in combination with heat from the surgical drill, over an extended period, is the most common cause of sinus thrombosis. In addition, the emissary vein, which drains into the sigmoid sinus, is encountered in the surgical approach and occlusion with prothrombotic material such as FloSeal (Baxter, Deerfield, Illinois, USA) may result in sinus thrombosis. Our current series highlights the utility of intraoperative MRI, which in 1 case provided a diagnosis of early CVST (Patient 2) and in another confirmed a previously missed preoperative finding (Patient 4). Although it is a rare occurrence, close attention should
REFERENCES 1. Beslow LA, Abend NS, Smith SE. Cerebral sinus venous thrombosis complicated by cerebellar hemorrhage in a child with acute promyelocytic leukemia. J Child Neurol. 2009;24:110-114. 2. Coutinho JM, Stam J, Canhão P, Barinagarrementeria F, Bousser MG, Ferro JM, et al. Cerebral venous thrombosis in the absence of headache. Stroke. 2015;46:245-247. 3. Thorell SE, Parry-Jones AR, Punter M, Hurford R, Thachil J. Cerebral venous thrombosis—a primer for the haematologist. Blood Rev. 2015;29:45-50. 4. Hannawi Y, Bershad E, Suarez J, Shaltoni H, Yoshor D, Venkatasubba Rao C. Post surgical
be paid to intraoperative images including postcontrast imaging through the sigmoid sinuses. It is our practice to discuss the findings of the intraoperative MRI with an attending neuroradiologist before closure for all cases involving this imaging modality. The management of early postoperative CVST is complicated by the risk of postoperative hemorrhage and wound healing issues. Though no evidence-based guidelines exist, treatment of CVST with full-dose anticoagulation appears to reduce the incidence of death and severe morbidity.22,23 A recent small series of lateral sinus thromboses after posterior fossa surgery, treated with anticoagulation, did not observe increased incidence of intracranial hemorrhage.24 Our anecdotal experience has been to proceed with therapeutic anticoagulation by postoperative day 3 or earlier depending on the severity of the thrombosis and the presumed risk of postoperative bleeding, but an individualized treatment decision must be made, carefully weighing risks and benefits of early postoperative anticoagulation. Luckily no patient in our series experienced symptoms related to their sinus thrombosis. In asymptomatic cases, although we err on the side of formal anticoagulation, the ideal treatment algorithm has not been evaluated. Close collaboration with hematology colleagues is necessary to weigh the risks and benefits in each individual case. CONCLUSIONS Cerebral venous sinus thrombosis may be associated with intracranial tumors in either the acute or late postoperative periods. Intraoperative MRI offers a useful tool to diagnose early CVST, which has important consequences for early postoperative anticoagulation treatment planning. Although rare, CVST may occur remotely from the site of low- and high-grade intracranial tumors, indicating that even benign intracranial neoplasms may induce a systemic prothrombotic state. However, the true incidence of this phenomenon remains unclear, and a prospective study to assess this issue may be warranted. While it is clear that CVST can cause significant morbidity, the clinical significance of asymptomatic imaging findings and necessity of treatment remain topics of debate. Guidelines have not been formulated for the ideal treatment in these asymptomatic cases, but close collaboration with a hematologist is recommended to fully consider the risks and benefits of therapeutic anticoagulation.
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and leptomeningeal carcinomatosis in a patient with ovarian cancer. J Clin Oncol. 2012;30:e19-e20. 8. Mazzoleni S, Putti MC, Simioni P, Sainati L, Tormene D, Manara R, et al. Early cerebral sinovenous thrombosis in a child with acute lymphoblastic leukemia carrying the prothrombin G20210A variant: a case report and review of the literature. Blood Coagul Fibrinolysis. 2005;16: 43-49. 9. Oda N, Sakugawa M, Bessho A, Horiuchi T, Hosokawa S, Toyota Y, et al. Cerebral venous sinus thrombosis concomitant with leptomeningeal carcinomatosis, in a patient with epidermal growth factor receptor-mutated lung cancer. Oncol Lett. 2014;8:2489-2492.
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REMOTE CVST IN PATIENTS WITH INTRACRANIAL TUMORS
16. Vargo JA, Snelling BM, Ghareeb ER, John K, Frame JN, Schmidt JH, et al. Dural venous sinus thrombosis in anaplastic astrocytoma following concurrent temozolomide and focal brain radiotherapy plus bevacizumab. J Neurooncol. 2011;104: 595-598. 17. Raza SM, Gallia GL, Brem H, Weingart JD, Long DM, Olivi A. Perioperative and long-term outcomes from the management of parasagittal meningiomas invading the superior sagittal sinus. Neurosurgery. 2010;67:885.
12. Song L, Lu H, Chang C, Li X, Zhang Z. Cerebral venous and sinus thrombosis in a patient with acute promyelocytic leukemia during all-trans retinoic acid induction treatment. Blood Coagul Fibrinolysis. 2014;25:773-776.
18. Lee KR, Subrayan V, Win MM, Fadhilah Mohamad N, Patel D. ATRA-induced cerebral sinus thrombosis. J Thromb Thrombolysis. 2014;38: 87-89.
13. Wang TY, Yen HJ, Hung GY, Hsieh MY, Tang RB. A rare complication in a child undergoing chemotherapy for acute lymphoblastic leukemia: superior sagittal sinus thrombosis. J Chin Med Assoc. 2011;74:183-187.
19. Saposnik G, Barinagarrementeria F, Brown RD, Bushnell CD, Cucchiara B, Cushman M, 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.
14. Pan E, Tsai JS, Mitchell SB. Retrospective study of venous thromboembolic and intracerebral hemorrhagic events in glioblastoma patients. Anticancer Res. 2009;29:4309-4313. 15. Redhu S, Mohd Abdul M, Pandey P, Devaragudi TS. Distant cerebral venous sinus thrombosis in meningioma surgery: a rare complication. Neurol India. 2013;61:180-181.
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low-molecular-weight heparin for cerebral sinus thrombosis. Stroke. 1999;30:484-488. 22. Coutinho JM, de Bruijn SF, deVeber G, Stam J. Anticoagulation for cerebral venous sinus thrombosis. Stroke. 2012;43:e41-e42. 23. Coutinho JM, Seelig R, Bousser MG, Canhao P, Ferro JM, Stam J. Treatment variations in cerebral venous thrombosis: an international survey. Cerebrovasc Dis. 2011;32:298-300. 24. Apra C, Kotbi O, Turc G, Corns R, Pages M, Souillard-Scemama R, et al. Presentation and management of lateral sinus thrombosis following posterior fossa surgery [e-pub ahead of print]. J Neurosurg. 2016:1-9; http://dx.doi.org/ 10.3171/2015.11.JNS151881.
Conflict of interest statement: The authors report no conflict of interest exists concerning the materials or methods used in this study or the findings specified in this paper. Received 23 September 2016; accepted 15 November 2016
20. Einhaupl KM, Villringer A, Meister W, Mehraein S, Garner C, Pellkofer M, et al. Heparin treatment in sinus venous thrombosis. Lancet. 1991;338:597-600.
Citation: World Neurosurg. (2017) 98:555-562. http://dx.doi.org/10.1016/j.wneu.2016.11.084
21. de Bruijn SF, Stam J. Randomized, placebocontrolled trial of anticoagulant treatment with
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