J Neurosurg Pediatrics 13:68–71, 2014 ©AANS, 2014
Endovascular thrombolysis for pediatric cerebral sinus venous thrombosis with tissue plasminogen activator and abciximab Case report Imad S. Khan, M.D.,1 Travis R. Ladner, B.A.,1 Komal F. Satti, M.D.,1 Moneeb Ehtesham, M.D.,1 Lori C. Jordan, M.D., Ph.D., 2 and Robert J. Singer, M.D. 2,3 Departments of 1Neurosurgery and 3Pediatric Neurology, Vanderbilt University Medical Center, Nashville, Tennessee; and 2Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire Cerebral sinus venous thrombosis (CSVT) is a relatively rare but potentially devastating disease. Medical management of CSVT with systemic anticoagulation has been the mainstay treatment strategy with these patients. However, some patients may not respond to this treatment or may present with very severe symptoms indicating more aggressive management strategies. The authors present the case of a pediatric patient who presented with severe CSVT, who underwent successful recanalization with endovascular tissue plasminogen activator (tPA) and abciximab. To the authors’ knowledge there are no cases of endovascular thrombolysis for CSVT described in the literature in which abciximab has been used in conjunction with tPA. The authors also review the literature regarding the agents used and outcome in pediatric patients with CSVT after endovascular thrombolysis. The use of abciximab in conjunction with tPA may be considered in patients whose blood is hypercoagulable and in whom the treatment strategy is to obtain acute recanalization and long-term venous patency. However, the use of adjunctive agents increases the risk of hemorrhagic complications and must be done judiciously. (http://thejns.org/doi/abs/10.3171/2013.9.PEDS13335)
Key Words • cerebral sinus venous thrombosis • abciximab • superior sagittal sinus thrombosis • tissue plasminogen activator • endovascular thrombolysis • vascular disorders
C
erebral sinus venous thrombosis (CSVT) results from a thrombosis of the cortical and deep veins or a thrombosis of the venous sinuses. The symptoms may range from a vague headache to a severe increase in intracranial pressure and herniation.4,5 The death and dependency rate for patients with CSVT ranges from 8.8% to 44.4%.18 The high rate of morbidity and mortality in patients with this condition makes timely diagnosis and treatment imperative. Medical management of CSVT with systemic anticoagulation has been the mainstay treatment strategy with these patients.16 However, some patients may not respond to this treatment or may present with very severe symptoms indicating more aggressive management strategies. This has led to the development of endovascular techniques to provide direct chemical or mechanical thrombolysis.15,21 Endovascular thrombolysis has the advantage of acute clot dissolution and decreased
Abbreviations used in this paper: CSVT = cerebral sinus venous thrombosis; ICH = intracerebral hemorrhage; SSS = superior sagittal sinus; SVG = saphenous vein graft; tPA = tissue plasminogen activator.
68
intracranial pressure due to normalization of cerebral blood drainage.18 Various authors have shown successful management of CSVT with endovascular treatment accompanied by the administration of urokinase or tissue plasminogen activator (tPA).18 Abciximab (a glycoprotein IIb/IIIa receptor antagonist) has shown promise in the treatment of experimental CSVT in rats, but to our knowledge there are no reported cases in which adjuvant tPA and abciximab have been used for the treatment of severe CSVT.20 We describe the case of a pediatric patient who presented with widespread thrombosis including CSVT, who underwent successful recanalization with endovascular tPA and abciximab administration.
Case Report History and Examination. This 16-year-old boy presented to the emergency room with a 3-week history of worsening headaches. He had a history of Stage III Hodgkin lymphoma with no B symptoms (he had completed therapy 6 years earlier). The headaches were right frontal J Neurosurg: Pediatrics / Volume 13 / January 2014
Endovascular thrombolysis for cerebral sinus venous thrombosis in location and were worst in the mornings. There was also some associated phonophobia, occasional nausea and vomiting, but no photophobia. For the last 3 days he had also noticed decreased sensation in the left arm and leg. On examination the patient was alert and oriented. Motor examination revealed left-sided weakness in the upper and lower extremities (4/5). There was a marked decrease of light touch sensation in the left arm and leg as well. Neuroimaging Investigation. Brain MRI and MR venogram depicted multiple areas of signal loss within the superior sagittal sinus (SSS), and right transverse and sigmoid sinus thrombosis (Fig. 1). The MRI study showed a small right parietal venous ischemic infarct but no hemorrhage. Further investigation also uncovered right popliteal and posterior tibial thrombosis and a thrombus in the right atrium. The patient was started on a heparin drip. Three days later, in spite of optimized heparin dosage, the left-sided weakness had worsened and an MRI study depicted a slight interval increase in the size of the parietal venous infarct. Based on the extent of sinus venous thrombosis and unresponsiveness to medical management, it was decided to treat this patient with transvenous thrombolysis of the SSS and right transverse sigmoid thrombosis.
Endovascular Management. A nick incision was made over the region on the right femoral artery, accessed with a single-wall needle technique. A Bentson wire was passed into the femoral vein and a 7-Fr sheath was placed in the vein connected to a continuous heparinized flush solution. The guide catheter was transnavigated through the transvenous route to the jugular bulb at the base of the skull on the right. A microcatheter was then transnavigated coaxially through the guide catheter over a 0.14 microwire to select the middle third of the SSS. The tPA and abciximab was then administered in 2-mg aliquots (total dosages: tPA 8 mg and abciximab 12 mg) and progressive revascularization of the SSS and right sigmoid sinus was effected. Control venous angiography confirmed complete revascularization of the sinuses (Fig. 2).
Posttreatment Course. The patient had gradual improvement in the left-sided weakness and paresthesias following the intervention, and there were no hemorrhagic complications. He was discharged to a rehabilita-
Fig. 1. Left: A reconstructed MR venogram depicting a noncontinuous SSS (arrows). Right: Sagittal T1-weighted MR image showing an isointense clot in the SSS (arrow).
J Neurosurg: Pediatrics / Volume 13 / January 2014
tion center 8 days later, and a CT venogram obtained 4 months posttreatment showed patent sinuses and no venous infarcts (Fig. 2). The patient has received 12 months of follow-up, with improving neurological status and no cognitive deficits.
Discussion
Although it is a relatively rare condition, CSVT is potentially devastating. The Canadian Pediatric Ischemic Stroke Registry reported an annual incidence of 0.34 cases of CSVT per 100,000 children, rising to 0.67 per 100,000 persons when neonates were included.7 This study reported death in 8% and neurological deficits in 41%. Malignancies are a risk factor for CSVT, and this condition is a known complication in the treatment for leukemia or non-Hodgkin lymphoma. Investigators at the Mayo Clinic recently reported an experience of 9 cases of CSVT in a retrospective sample of 200 patients with acute lymphoblastic leukemia or non-Hodgkin lymphoma. All patients had previously been treated with l-asparaginase.19 Each patient’s CSVT was treated with lowmolecular-weight heparin. Of the 4 patients who were available for long-term follow-up, all had normal or nearnormal neuropsychological outcomes. Systemic anticoagulation has been the mainstay in the treatment of CSVT; however, cases in which medical management has been unsuccessful or emergency intervention is required have driven the development of direct thrombolytic therapy via microcatheter.18 Although there have been no randomized controlled trials as of this writing, patients receiving direct thrombolysis with urokinase or tPA have generally experienced excellent recovery. Mechanical thrombectomy is another option that is currently undergoing clinical investigation. There are only a few cases of direct thrombolysis for CSVT in children, and these are mostly documented in case reports or small case series. Most practitioners have used urokinase, which has been replaced by tPA in recent years (Table 1). These patients generally have favorable outcomes, with excellent recovery and no associated iatrogenic intracerebral hemorrhage (ICH). However, the long-term outcomes in these patients have only rarely been reported in the literature. We could find no previous reports in the cerebrovascular literature of adjuvant local abciximab being used with tPA for the management of CSVT. Röttger and colleagues20 studied the effect of intravenous abciximab in experimentally induced SSS thrombosis in rats, and found that compared with tPA and enoxaparin, abciximab had the best clinical outcome and the most prolonged progressive recanalization beyond the 1st postoperative day. A recent nonrandomized prospective study of intravenous abciximab used in conjunction with intraarterial tPA in 20 patients with vertebrobasilar occlusion found that it yielded a high recanalization rate (85%).2 Another study of 47 prospective patients found that those who received this combination, with the addition of percutaneous transluminal angioplasty and/or stent insertion for severe residual stenosis, had improved neurological outcomes over a retrospective cohort treated by tPA alone (34% vs 17%).8 69
I. S. Khan et al.
Fig. 2. A: A pretreatment superselective venogram showing decreased drainage of the SSS. B: A posttreatment venogram showing evidence of improved patency around a small residual clot. C: A CT venogram obtained 4 months posttreatment showing continued patency of the SSS.
The management of CSVT with endovascular thrombolysis carries the risk of hemorrhagic complications, especially if a combination of drugs is used. Qureshi et al.17 reported on 7 patients who developed ICHs associated with neurointerventional procedures in which a combination of antithrombotic agents including abciximab were used. It is important to note, however, that the patients reported in that series had angio-occlusive disease leading to a high risk of reperfusion injury with intervention. The use of multiple antithrombotic drugs in this setting may greatly increase the risk of ICH. Abciximab has shown promise when used to treat thrombo-occlusive saphenous vein graft (SVG) disease after cardiac bypass surgery. Pretreatment with abciximab has been shown to decrease the thrombus burden in the SVG before percutaneous intervention is attempted.3
Routine use of abciximab for elective percutaneous coronary intervention to reopen thrombosed SVGs has also been shown to improve the long-term outcome in patients with diabetes (who have historically had worse outcomes than nondiabetic patients).1 Kirby and colleagues14 also noted the long-term efficacy of abciximab in preventing reocclusion of venous thrombosis. They reported a small case series of critically ill pediatric patients who underwent mechanical thrombectomy with abciximab administration for central venous thrombosis. Their intervention led to a near-normal venous flow pattern and subsequent long-term normal central veins in most of their patients. Our patient had a history of Hodgkin lymphoma and had developed venous thrombosis in various parts of his body, with no known precipitating factors. In patients with this hypercoagulable state, we believe that supplementing tPA
TABLE 1: Literature review of pediatric cases of CSVT treated with endovascular thrombolysis* No. of Cases
Age, Sex
Higashida et al., 1989 Griesemer et al., 1994
1 1
10 yrs, M
urokinase urokinase
Gebara et al., 1995 Del-Rio Camacho et al., 2001 Gebara & Everett, 2001 Zerah et al., 2007 Wasay et al., 2006
1 1
9 wks, F 3 yrs, F
urokinase rtPA
1 1 3
10 days, M
Authors & Year
4 yrs, M 12 yrs, F 3.5 wks, M
Philips et al., 1999 Wasay et al., 2001 Horowitz et al., 1995
1 1 2
14 yrs, F 4 yrs, M 6 wks, F 12 yrs, F
Agent
Dose 1000 U/hr × 2 hrs 470,000 U/75 mins
25,000 U/10 mins × 7 0.2-mg/kg bolus, 0.5 mg/kg/hr × 3 hrs urokinase 125,000 U/80 mins tPA 55-mg bolus, 3 mg/hr × 24 hrs urokinase 50,000-U bolus, 5000 U/hr urokinase 250,000-U bolus, 60,000 U/hr × 41 hrs urokinase + tPA 30,000 U urokinase, 0.5 mg/kg/ hr tPA urokinase 200,000 U urokinase 50,000-U bolus, 10,000 U/hr urokinase 50,000-U bolus, 10,000–20,000 U/hr × 84 hrs urokinase 500,000-U bolus, 60,000 U/hr × 72 hrs
Outcome normal development at 3 yrs normal, except weakness of rt tri ceps & rt ankle dorsiflexion normal normal excellent excellent normal normal, but w/ papilledema on dis charge death 6 hrs after tPA infusion w/o hemorrhage excellent normal on discharge NA excellent
FU 6 wks 9 mos 2 yrs 2 wks 1 day NA NA NA NA NA NA
* FU = follow-up; NA = not applicable; rtPA = recombinant tPA.
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J Neurosurg: Pediatrics / Volume 13 / January 2014
Endovascular thrombolysis for cerebral sinus venous thrombosis with abciximab for endovascular thrombolysis increases the chances of obtaining long-term recanalization. Endovascular thrombolysis is a safe and effective treatment modality in pediatric patients with severe symptomatic CSVT. The use of abciximab in conjunction with tPA may be considered in patients whose blood is hypercoagulable, and in whom the treatment strategy is to obtain acute recanalization and long-term venous patency. However, the use of adjunctive agents increases the risk of hemorrhagic complications and must be done judiciously. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author contributions to the study and manuscript preparation include the following. Conception and design: Singer, Khan, Ladner, Jordan. Acquisition of data: Khan, Ladner, Satti, Ehtesham, Jordan. Drafting the article: Khan, Ladner, Satti, Ehtesham. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Singer. Study supervision: Singer. References 1. Applegate RJ, Upadhya B, Little WC, Xenakis M, Gandhi SK, Baki TT, et al: Late outcomes after intervention of vein grafts in diabetics with abciximab use. Int J Cardiol 111:136–141, 2006 2. Barlinn K, Becker U, Puetz V, Dzialowski I, Kunz A, Kepplinger J, et al: Combined treatment with intravenous abciximab and intraarterial tPA yields high recanalization rate in patients with acute basilar artery occlusion. J Neuroimaging 22:167–171, 2012 3. Barsness GW, Buller C, Ohman EM, Schechter E, Pucillo A, Taylor MA, et al: Reduced thrombus burden with abciximab delivered locally before percutaneous intervention in saphenous vein grafts. Am Heart J 139:824–829, 2000 4. Ciccone A, Canhão P, Falcão F, Ferro JM, Sterzi R: Thrombolysis for cerebral vein and dural sinus thrombosis. Cochrane Database Syst Rev (1):CD003693, 2004 5. Cumurciuc R, Crassard I, Sarov M, Valade D, Bousser MG: Headache as the only neurological sign of cerebral venous thrombosis: a series of 17 cases. J Neurol Neurosurg Psychiatry 76:1084–1087, 2005 6. Del-Rio Camacho G, Orozco AL, Pérez-Higueras A, Camino López M, Al-Assir I, Ruiz-Moreno M: Moyamoya disease and sagittal sinus thrombosis in a child with Down’s syndrome. Pediatr Radiol 31:125–128, 2001 7. deVeber G, Andrew M, Adams C, Bjornson B, Booth F, Buckley DJ, et al: Cerebral sinovenous thrombosis in children. N Engl J Med 345:417–423, 2001 8. Eckert B, Koch C, Thomalla G, Kucinski T, Grzyska U, Roether J, et al: Aggressive therapy with intravenous abciximab and intra-arterial rtPA and additional PTA/stenting improves clinical outcome in acute vertebrobasilar occlusion: combined local fibrinolysis and intravenous abciximab in acute vertebrobasilar stroke treatment (FAST): results of a multicenter study. Stroke 36:1160–1165, 2005 9. Gebara BM, Everett KO: Dural sinus thrombosis complicat-
J Neurosurg: Pediatrics / Volume 13 / January 2014
ing hypernatremic dehydration in a breastfed neonate. Clin Pediatr (Phila) 40:45–48, 2001 10. Gebara BM, Goetting MG, Wang AM: Dural sinus thrombosis complicating subclavian vein catheterization: treatment with local thrombolysis. Pediatrics 95:138–140, 1995 11. Griesemer DA, Theodorou AA, Berg RA, Spera TD: Local fibrinolysis in cerebral venous thrombosis. Pediatr Neurol 10: 78–80, 1994 12. Higashida RT, Helmer E, Halbach VV, Hieshima GB: Direct thrombolytic therapy for superior sagittal sinus thrombosis. AJNR Am J Neuroradiol 10 (5 Suppl):S4–S6, 1989 13. Horowitz M, Purdy P, Unwin H, Carstens G III, Greenlee R, Hise J, et al: Treatment of dural sinus thrombosis using selective catheterization and urokinase. Ann Neurol 38:58–67, 1995 14. Kirby WC, D’Sa R, Shapiro SR: Mechanical thrombectomy for treatment of postoperative venous obstruction in pediatric patients. J Invasive Cardiol 16 (5 Suppl):27S–29S, 2004 15. Persson L, Lilja A: Extensive dural sinus thrombosis treated by surgical removal and local streptokinase infusion. Neurosurgery 26:117–121, 1990 16. Philips MF, Bagley LJ, Sinson GP, Raps EC, Galetta SL, Zager EL, et al: Endovascular thrombolysis for symptomatic cerebral venous thrombosis. J Neurosurg 90:65–71, 1999 17. Qureshi AI, Saad M, Zaidat OO, Suarez JI, Alexander MJ, Fareed M, et al: Intracerebral hemorrhages associated with neurointerventional procedures using a combination of antithrombotic agents including abciximab. Stroke 33:1916–1919, 2002 18. Rahman M, Velat GJ, Hoh BL, Mocco J: Direct thrombolysis for cerebral venous sinus thrombosis. Neurosurg Focus 27(5): E7, 2009 19. Ross CS, Brown TM, Kotagal S, Rodriguez V: Cerebral venous sinus thrombosis in pediatric cancer patients: long-term neurological outcomes. J Pediatr Hematol Oncol 35:299–302, 2013 20. Röttger C, Madlener K, Heil M, Gerriets T, Walberer M, Wessels T, et al: Is heparin treatment the optimal management for cerebral venous thrombosis? Effect of abciximab, recombinant tissue plasminogen activator, and enoxaparin in experimentally induced superior sagittal sinus thrombosis. Stroke 36:841–846, 2005 21. Sindou M, Mercier P, Bokor J, Brunon J: Bilateral thrombosis of the transverse sinuses: microsurgical revascularization with venous bypass. Surg Neurol 13:215–220, 1980 22. Wasay M, Bakshi R, Dai A, Roach S: Local thrombolytic treatment of cerebral venous thrombosis in three paediatric patients. J Pak Med Assoc 56:555–556, 2006 23. Wasay M, Bakshi R, Kojan S, Bobustuc G, Dubey N, Unwin DH: Nonrandomized comparison of local urokinase thrombolysis versus systemic heparin anticoagulation for superior sagittal sinus thrombosis. Stroke 32:2310–2317, 2001 24. Zerah M, Patterson R, Hansen I, Briones M, Dion J, Renfroe B: Resolution of severe sinus vein thrombosis with super selective thrombolysis in a pre-adolescent with diabetic ketoacidosis and a prothrombin gene mutation. J Pediatr Endocrinol Metab 20:725–731, 2007 Manuscript submitted June 28, 2013. Accepted September 24, 2013. Please include this information when citing this paper: published online November 1, 2013; DOI: 10.3171/2013.9.PEDS13335. Address correspondence to: Robert J. Singer, M.D., Neurovascular Therapeutics, Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, 1 Medical Center Dr., Lebanon, NH 03756. email: [email protected].
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Endovascular thrombolysis for pediatric cerebral sinus venous thrombosis with tissue plasminogen activator and abciximab Case report Imad S. Khan, M.D.,1 Travis R. Ladner, B.A.,1 Komal F. Satti, M.D.,1 Moneeb Ehtesham, M.D.,1 Lori C. Jordan, M.D., Ph.D., 2 and Robert J. Singer, M.D. 2,3 Departments of 1Neurosurgery and 3Pediatric Neurology, Vanderbilt University Medical Center, Nashville, Tennessee; and 2Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire Cerebral sinus venous thrombosis (CSVT) is a relatively rare but potentially devastating disease. Medical management of CSVT with systemic anticoagulation has been the mainstay treatment strategy with these patients. However, some patients may not respond to this treatment or may present with very severe symptoms indicating more aggressive management strategies. The authors present the case of a pediatric patient who presented with severe CSVT, who underwent successful recanalization with endovascular tissue plasminogen activator (tPA) and abciximab. To the authors’ knowledge there are no cases of endovascular thrombolysis for CSVT described in the literature in which abciximab has been used in conjunction with tPA. The authors also review the literature regarding the agents used and outcome in pediatric patients with CSVT after endovascular thrombolysis. The use of abciximab in conjunction with tPA may be considered in patients whose blood is hypercoagulable and in whom the treatment strategy is to obtain acute recanalization and long-term venous patency. However, the use of adjunctive agents increases the risk of hemorrhagic complications and must be done judiciously. (http://thejns.org/doi/abs/10.3171/2013.9.PEDS13335)
Key Words • cerebral sinus venous thrombosis • abciximab • superior sagittal sinus thrombosis • tissue plasminogen activator • endovascular thrombolysis • vascular disorders
C
erebral sinus venous thrombosis (CSVT) results from a thrombosis of the cortical and deep veins or a thrombosis of the venous sinuses. The symptoms may range from a vague headache to a severe increase in intracranial pressure and herniation.4,5 The death and dependency rate for patients with CSVT ranges from 8.8% to 44.4%.18 The high rate of morbidity and mortality in patients with this condition makes timely diagnosis and treatment imperative. Medical management of CSVT with systemic anticoagulation has been the mainstay treatment strategy with these patients.16 However, some patients may not respond to this treatment or may present with very severe symptoms indicating more aggressive management strategies. This has led to the development of endovascular techniques to provide direct chemical or mechanical thrombolysis.15,21 Endovascular thrombolysis has the advantage of acute clot dissolution and decreased
Abbreviations used in this paper: CSVT = cerebral sinus venous thrombosis; ICH = intracerebral hemorrhage; SSS = superior sagittal sinus; SVG = saphenous vein graft; tPA = tissue plasminogen activator.
68
intracranial pressure due to normalization of cerebral blood drainage.18 Various authors have shown successful management of CSVT with endovascular treatment accompanied by the administration of urokinase or tissue plasminogen activator (tPA).18 Abciximab (a glycoprotein IIb/IIIa receptor antagonist) has shown promise in the treatment of experimental CSVT in rats, but to our knowledge there are no reported cases in which adjuvant tPA and abciximab have been used for the treatment of severe CSVT.20 We describe the case of a pediatric patient who presented with widespread thrombosis including CSVT, who underwent successful recanalization with endovascular tPA and abciximab administration.
Case Report History and Examination. This 16-year-old boy presented to the emergency room with a 3-week history of worsening headaches. He had a history of Stage III Hodgkin lymphoma with no B symptoms (he had completed therapy 6 years earlier). The headaches were right frontal J Neurosurg: Pediatrics / Volume 13 / January 2014
Endovascular thrombolysis for cerebral sinus venous thrombosis in location and were worst in the mornings. There was also some associated phonophobia, occasional nausea and vomiting, but no photophobia. For the last 3 days he had also noticed decreased sensation in the left arm and leg. On examination the patient was alert and oriented. Motor examination revealed left-sided weakness in the upper and lower extremities (4/5). There was a marked decrease of light touch sensation in the left arm and leg as well. Neuroimaging Investigation. Brain MRI and MR venogram depicted multiple areas of signal loss within the superior sagittal sinus (SSS), and right transverse and sigmoid sinus thrombosis (Fig. 1). The MRI study showed a small right parietal venous ischemic infarct but no hemorrhage. Further investigation also uncovered right popliteal and posterior tibial thrombosis and a thrombus in the right atrium. The patient was started on a heparin drip. Three days later, in spite of optimized heparin dosage, the left-sided weakness had worsened and an MRI study depicted a slight interval increase in the size of the parietal venous infarct. Based on the extent of sinus venous thrombosis and unresponsiveness to medical management, it was decided to treat this patient with transvenous thrombolysis of the SSS and right transverse sigmoid thrombosis.
Endovascular Management. A nick incision was made over the region on the right femoral artery, accessed with a single-wall needle technique. A Bentson wire was passed into the femoral vein and a 7-Fr sheath was placed in the vein connected to a continuous heparinized flush solution. The guide catheter was transnavigated through the transvenous route to the jugular bulb at the base of the skull on the right. A microcatheter was then transnavigated coaxially through the guide catheter over a 0.14 microwire to select the middle third of the SSS. The tPA and abciximab was then administered in 2-mg aliquots (total dosages: tPA 8 mg and abciximab 12 mg) and progressive revascularization of the SSS and right sigmoid sinus was effected. Control venous angiography confirmed complete revascularization of the sinuses (Fig. 2).
Posttreatment Course. The patient had gradual improvement in the left-sided weakness and paresthesias following the intervention, and there were no hemorrhagic complications. He was discharged to a rehabilita-
Fig. 1. Left: A reconstructed MR venogram depicting a noncontinuous SSS (arrows). Right: Sagittal T1-weighted MR image showing an isointense clot in the SSS (arrow).
J Neurosurg: Pediatrics / Volume 13 / January 2014
tion center 8 days later, and a CT venogram obtained 4 months posttreatment showed patent sinuses and no venous infarcts (Fig. 2). The patient has received 12 months of follow-up, with improving neurological status and no cognitive deficits.
Discussion
Although it is a relatively rare condition, CSVT is potentially devastating. The Canadian Pediatric Ischemic Stroke Registry reported an annual incidence of 0.34 cases of CSVT per 100,000 children, rising to 0.67 per 100,000 persons when neonates were included.7 This study reported death in 8% and neurological deficits in 41%. Malignancies are a risk factor for CSVT, and this condition is a known complication in the treatment for leukemia or non-Hodgkin lymphoma. Investigators at the Mayo Clinic recently reported an experience of 9 cases of CSVT in a retrospective sample of 200 patients with acute lymphoblastic leukemia or non-Hodgkin lymphoma. All patients had previously been treated with l-asparaginase.19 Each patient’s CSVT was treated with lowmolecular-weight heparin. Of the 4 patients who were available for long-term follow-up, all had normal or nearnormal neuropsychological outcomes. Systemic anticoagulation has been the mainstay in the treatment of CSVT; however, cases in which medical management has been unsuccessful or emergency intervention is required have driven the development of direct thrombolytic therapy via microcatheter.18 Although there have been no randomized controlled trials as of this writing, patients receiving direct thrombolysis with urokinase or tPA have generally experienced excellent recovery. Mechanical thrombectomy is another option that is currently undergoing clinical investigation. There are only a few cases of direct thrombolysis for CSVT in children, and these are mostly documented in case reports or small case series. Most practitioners have used urokinase, which has been replaced by tPA in recent years (Table 1). These patients generally have favorable outcomes, with excellent recovery and no associated iatrogenic intracerebral hemorrhage (ICH). However, the long-term outcomes in these patients have only rarely been reported in the literature. We could find no previous reports in the cerebrovascular literature of adjuvant local abciximab being used with tPA for the management of CSVT. Röttger and colleagues20 studied the effect of intravenous abciximab in experimentally induced SSS thrombosis in rats, and found that compared with tPA and enoxaparin, abciximab had the best clinical outcome and the most prolonged progressive recanalization beyond the 1st postoperative day. A recent nonrandomized prospective study of intravenous abciximab used in conjunction with intraarterial tPA in 20 patients with vertebrobasilar occlusion found that it yielded a high recanalization rate (85%).2 Another study of 47 prospective patients found that those who received this combination, with the addition of percutaneous transluminal angioplasty and/or stent insertion for severe residual stenosis, had improved neurological outcomes over a retrospective cohort treated by tPA alone (34% vs 17%).8 69
I. S. Khan et al.
Fig. 2. A: A pretreatment superselective venogram showing decreased drainage of the SSS. B: A posttreatment venogram showing evidence of improved patency around a small residual clot. C: A CT venogram obtained 4 months posttreatment showing continued patency of the SSS.
The management of CSVT with endovascular thrombolysis carries the risk of hemorrhagic complications, especially if a combination of drugs is used. Qureshi et al.17 reported on 7 patients who developed ICHs associated with neurointerventional procedures in which a combination of antithrombotic agents including abciximab were used. It is important to note, however, that the patients reported in that series had angio-occlusive disease leading to a high risk of reperfusion injury with intervention. The use of multiple antithrombotic drugs in this setting may greatly increase the risk of ICH. Abciximab has shown promise when used to treat thrombo-occlusive saphenous vein graft (SVG) disease after cardiac bypass surgery. Pretreatment with abciximab has been shown to decrease the thrombus burden in the SVG before percutaneous intervention is attempted.3
Routine use of abciximab for elective percutaneous coronary intervention to reopen thrombosed SVGs has also been shown to improve the long-term outcome in patients with diabetes (who have historically had worse outcomes than nondiabetic patients).1 Kirby and colleagues14 also noted the long-term efficacy of abciximab in preventing reocclusion of venous thrombosis. They reported a small case series of critically ill pediatric patients who underwent mechanical thrombectomy with abciximab administration for central venous thrombosis. Their intervention led to a near-normal venous flow pattern and subsequent long-term normal central veins in most of their patients. Our patient had a history of Hodgkin lymphoma and had developed venous thrombosis in various parts of his body, with no known precipitating factors. In patients with this hypercoagulable state, we believe that supplementing tPA
TABLE 1: Literature review of pediatric cases of CSVT treated with endovascular thrombolysis* No. of Cases
Age, Sex
Higashida et al., 1989 Griesemer et al., 1994
1 1
10 yrs, M
urokinase urokinase
Gebara et al., 1995 Del-Rio Camacho et al., 2001 Gebara & Everett, 2001 Zerah et al., 2007 Wasay et al., 2006
1 1
9 wks, F 3 yrs, F
urokinase rtPA
1 1 3
10 days, M
Authors & Year
4 yrs, M 12 yrs, F 3.5 wks, M
Philips et al., 1999 Wasay et al., 2001 Horowitz et al., 1995
1 1 2
14 yrs, F 4 yrs, M 6 wks, F 12 yrs, F
Agent
Dose 1000 U/hr × 2 hrs 470,000 U/75 mins
25,000 U/10 mins × 7 0.2-mg/kg bolus, 0.5 mg/kg/hr × 3 hrs urokinase 125,000 U/80 mins tPA 55-mg bolus, 3 mg/hr × 24 hrs urokinase 50,000-U bolus, 5000 U/hr urokinase 250,000-U bolus, 60,000 U/hr × 41 hrs urokinase + tPA 30,000 U urokinase, 0.5 mg/kg/ hr tPA urokinase 200,000 U urokinase 50,000-U bolus, 10,000 U/hr urokinase 50,000-U bolus, 10,000–20,000 U/hr × 84 hrs urokinase 500,000-U bolus, 60,000 U/hr × 72 hrs
Outcome normal development at 3 yrs normal, except weakness of rt tri ceps & rt ankle dorsiflexion normal normal excellent excellent normal normal, but w/ papilledema on dis charge death 6 hrs after tPA infusion w/o hemorrhage excellent normal on discharge NA excellent
FU 6 wks 9 mos 2 yrs 2 wks 1 day NA NA NA NA NA NA
* FU = follow-up; NA = not applicable; rtPA = recombinant tPA.
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Endovascular thrombolysis for cerebral sinus venous thrombosis with abciximab for endovascular thrombolysis increases the chances of obtaining long-term recanalization. Endovascular thrombolysis is a safe and effective treatment modality in pediatric patients with severe symptomatic CSVT. The use of abciximab in conjunction with tPA may be considered in patients whose blood is hypercoagulable, and in whom the treatment strategy is to obtain acute recanalization and long-term venous patency. However, the use of adjunctive agents increases the risk of hemorrhagic complications and must be done judiciously. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author contributions to the study and manuscript preparation include the following. Conception and design: Singer, Khan, Ladner, Jordan. Acquisition of data: Khan, Ladner, Satti, Ehtesham, Jordan. Drafting the article: Khan, Ladner, Satti, Ehtesham. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Singer. Study supervision: Singer. References 1. Applegate RJ, Upadhya B, Little WC, Xenakis M, Gandhi SK, Baki TT, et al: Late outcomes after intervention of vein grafts in diabetics with abciximab use. Int J Cardiol 111:136–141, 2006 2. Barlinn K, Becker U, Puetz V, Dzialowski I, Kunz A, Kepplinger J, et al: Combined treatment with intravenous abciximab and intraarterial tPA yields high recanalization rate in patients with acute basilar artery occlusion. J Neuroimaging 22:167–171, 2012 3. Barsness GW, Buller C, Ohman EM, Schechter E, Pucillo A, Taylor MA, et al: Reduced thrombus burden with abciximab delivered locally before percutaneous intervention in saphenous vein grafts. Am Heart J 139:824–829, 2000 4. Ciccone A, Canhão P, Falcão F, Ferro JM, Sterzi R: Thrombolysis for cerebral vein and dural sinus thrombosis. Cochrane Database Syst Rev (1):CD003693, 2004 5. Cumurciuc R, Crassard I, Sarov M, Valade D, Bousser MG: Headache as the only neurological sign of cerebral venous thrombosis: a series of 17 cases. J Neurol Neurosurg Psychiatry 76:1084–1087, 2005 6. Del-Rio Camacho G, Orozco AL, Pérez-Higueras A, Camino López M, Al-Assir I, Ruiz-Moreno M: Moyamoya disease and sagittal sinus thrombosis in a child with Down’s syndrome. Pediatr Radiol 31:125–128, 2001 7. deVeber G, Andrew M, Adams C, Bjornson B, Booth F, Buckley DJ, et al: Cerebral sinovenous thrombosis in children. N Engl J Med 345:417–423, 2001 8. Eckert B, Koch C, Thomalla G, Kucinski T, Grzyska U, Roether J, et al: Aggressive therapy with intravenous abciximab and intra-arterial rtPA and additional PTA/stenting improves clinical outcome in acute vertebrobasilar occlusion: combined local fibrinolysis and intravenous abciximab in acute vertebrobasilar stroke treatment (FAST): results of a multicenter study. Stroke 36:1160–1165, 2005 9. Gebara BM, Everett KO: Dural sinus thrombosis complicat-
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