There is increasing evidence that local thrombolysis can be used with relative safety and efficacy in adults with superior sagittal sinus thrombosis (SSST). However, little data is available on the use of local thrombolysis in children with SSST. We report three patients who received local thrombolysis for dural sinus thrombosis. Two patients received urokinase and one patient received urokinase followed by local TPA infusion. Recanalization was achieved in two patients

Bakshi, Rohit

Dai, Alper

Roach, Steve

Wasay, Mohammad

English

eCommons@AKU

eCommons@AKUSection of Neurology Department of MedicineNovember 2006Local thrombolytic treatment of cerebral venousthrombosis in three paediatric patientsMohammad WasayAga Khan University, mohammad.wasay@aku.eduRohit BakshiAlper DaiSteve RoachFollow this and additional works at: https://ecommons.aku.edu/pakistan_fhs_mc_med_neurolPart of the Neurology CommonsRecommended CitationWasay, M., Bakshi, R., Dai, A., Roach, S. (2006). Local thrombolytic treatment of cerebral venous thrombosis in three paediatricpatients. Journal of Pakistan Medical Association, 56(11), 555-556.Available at: https://ecommons.aku.edu/pakistan_fhs_mc_med_neurol/160Case ReportLocal thrombolytic treatment of Cerebral Venous Thrombosis in three paediatricpatientsMohammad Wasay1, Rohit Bakshi2, Alper Dai3, Steve Roach4Department of Neurology, The Aga Khan University, Karachi1, Harvard University, Brigham and women Hospital, Boston2, Gaziantep University,Gaziantep, Turkey3, Ohio State University School of Medicine4, Columbus, OH.AbstractThere is increasing evidence that local thrombolysiscan be used with relative safety and efficacy in adults withsuperior sagittal sinus thrombosis (SSST). However, little datais available on the use of local thrombolysis in children withSSST. We report three patients who received local thromboly-sis for dural sinus thrombosis. Two patients received urokinaseand one patient received urokinase followed by local TPA infu-sion. Recanalization was achieved in two patients. IntroductionSuperior sagittal sinus thrombosis (SST) is uncommonin children. Several treatment protocols have been used fortreatment of paediatric SST, including hydration, antibiotics,steroids, diuretics, osmotic agents, antiplatelet therapy, systemicanticoagulation and systemic and local thrombolysis.1-3 The useof TPA in paediatric SST has not been reported but there are afew reported cases of urokinase thrombolysis in these patients.We report three patients with dural sinus thrombosis. Twopatients received locally administered urokinase and the otherwas treated with local TPA infusion. One of these patients wasreferred to briefly in a recent large series.4Case ReportPatient 1: A four-year-old boy with nephrotic syndrome pre-sented with headache and irritability. General physical andneurologic examinations were unremarkable except forlethargy. Head CT showed hyperdensity of the superior sagit-tal sinus (SSS) and straight sinus (StS). MRI with MR venog-raphy (MRV) showed thrombosis of the SSS and the straightsinus (StS). Catheter angiography confirmed thrombosis ofSSS, StS and left transverse sinus (TS). An angiographiccatheter was placed into internal jugular vein via transfemoralcatheterization. A Tracker -18 microcatheter (TargetTherapeutics, CA) was advanced through angiographiccatheter into the superior sagittal sinus. The patient receiveda bolus of urokinase (50,000 units) into SSS. The catheter wasretained in the SSS and urokinase was infused continuouslyat 5000 units per hour. A repeat angiogram 20 hours latershowed patency of SSS. There were no complications. Patientwas subsequently started on oral warfarin. He was dischargedwith a normal neurologic status. Patient 2: A 12-year-old girl with systemic lupus erythemato-sus and lupus nephritis presented with headache and difficultywith ambulation. Neurologic examination showed papilloede-ma and gait ataxia. Her laboratory evaluation was unremark-able except for an elevated prothrombin time (23.8 seconds)and positive antiphospholipid antibodies. Brain MRI/MRVshowed small bilateral subdural haematomas and thrombosisof superior sagittal sinus, straight sinus and right transversesinus. Catheter angiography confirmed the MRV findings.Intravenous heparin was started but there was no neurologicimprovement after 24 hours. A 5F angiographic catheter wasplaced through femoral vein catheterization. A Tracker-18microcatheter was advanced into SSS through the angiograph-ic catheter. The patient received a bolus of urokinase (250,000units) into the SSS followed by continuous infusion at 60,000units per hour for 41 hours. A repeat angiogram showedrecanalization of SSS. She required blood transfusion due tofalling haematocrit. She was discharged home on warfarin witha normal neurologic exam but still had papilloedema.Patient 3: A 3-½ week old boy who had prolonged hypogly-caemia at birth was admitted with lethargy and poor oralintake. Initial neurologic examination was unremarkableexcept for lethargy. The hospital course was complicated bysepsis, acute renal failure, disseminated intravascular coagu-lation (DIC), myocarditis and seizures. Head CT scanshowed a right frontal intraparenchymal haemorrhage.Cerebral angiography showed thrombosis of the SuperiorSagittal Sinus, Transverse Sinus, Sigmoid sinus, and internaljugular vein. A Tracker-18 catheter was advanced into SSSthrough transfemoral angiographic catheter. He received abolus of urokinase (30,000 units) into the SSS followed bylocal TPA infusion at 0.5 mg/kg/hour. Recanalization wasnot achieved. The patient died six hours after TPA infusion.An autopsy showed cardiomyopathy, extensive dural venoussinus thrombosis and pulmonary artery thrombosis, withoutevidence of haemorrhagic complications.DiscussionA growing body of evidence suggests that localVol. 56, No. 11, November 2006 555urokinase thrombolysis is relatively safe and effec-tive in adult patients with cerebral venous thrombosis(CVT). Horowitz et al.3 reported 13 patients including a 12-year-old boy treated with local urokinase thrombolysis. In areview of 20 patients with SSST, Wasay et al.4 found localurokinase thrombolysis to be relatively safe and effective.Local thrombolysis using recombinant tissue plasminogenactivator (TPA) has been suggested recently as an alterna-tive to urokinase. Kim et al.5 reported nine adult patientswith dural sinus thrombosis treated with local TPA withexcellent outcome. Frey et al.6 summarized 12 adult patientswith cerebral venous thrombosis who were treated withcombined intrathrombus rtPa and intravenous heparin. Ninepatients had significant clinical improvement. Two patientsshowed worsening of haemorrhage.  CVT in children causes significant morbidity andmortality. One literature review found a16% mortality and22% with long term disability in paediatric patients withCVT. Supportive care without anticoagulation is the main-stay of treatment in most cases characterized by limitedthrombosis.7 A recent study of 22 paediatric patients withCVT showed intravenous heparin or low molecular weightheparin (LMWH) to be safe and effective.2 The experiencewith  thrombolytic therapy in paediatric CVT is limited to afew case reports.8-10 Griesmer et al8 reported a 10-year-oldboy with SSST, TST, StS and sigmiod sinus thrombosis.Due to progressive neurological deterioration he was treat-ed with local Urokinase thrombolysis with dramaticimprovement. Wong et al.9 reported a one-day-old neonatewith parasagittal haemorrhage due to cortical vein thrombo-sis. The patient recovered completely after local urokinasethrombolysis. Gebara et al.10 reported a nine-week old girlwith dural sinus thrombosis secondary to subclavian veincatheterization. She had complete recovery after localurokinase thrombolysis.Anticoagulation is commonly used for adult patientswith SSST; however anticoagulation may not ensure neuro-logic recovery. There is a growing interest in the use of localthrombolysis with urokinase or TPA for CVT. More than 90adult cases of CVT treated with local thrombolysis havebeen reported in literature.4 Because of important matura-tional differences in cerebrovascular and coagulational sys-tems of infants and children compared with adults, therapiesthat had been proven to be safe and effective in adultpatients may not be directly extrapolated to the paediatricage group.One of our children had nephrotic syndrome and anoth-er had lupus nephritis. A hypercoaguable state in nephroticsyndrome is probably related to functional anti-thrombin IIIdeficiency. Because mechanism of heparin is based on anti-thrombin III activity, its effects are variable in patients withnephrotic syndrome. Due to extensive thrombosis and comor-bidity, local thrombolytic therapy was chosen. Collagen vascular disease is a well-known risk fac-tor for CVT. Local thrombolytic therapy has been used pre-viously in adult patients with SLE. Despite the presence ofsmall SDH, thrombolysis was used in the second patientbecause of progressive neurological deterioration despiteheparinization. Her symptoms improved after local throm-bolysis. The third patient had extensive comorbidity andthromboses of multiple dural sinuses. When patency of SSSwas not achieved with urokinase bolus he was switched totPa infusion. His death was unrelated to either his duralsinus thrombosis or to the thrombolytic therapy but it wasdue to his overwhelming systemic illness. No new intracra-nial haemorrhage or worsening of frontal haematoma wasidentified on autopsy.Our study shows the safety of local urokinase throm-bolysis in three children with CVT despite the presence ofpreexisting intracranial haemorrhages in two patients. Thethrombolysis led to recanalization and neurologic recoveryin two cases. The poor outcome in the third patient wasmost likely due to the underlying systemic illness. Localthrombolysis appears to be reasonably safe in children withCVT and deteriorating neurologic status. However, firmconclusions should await further experience and prospec-tive randomized trials.References1. Roach ES, Riela AR. Sinovenous occlusion; in Roach ES, Riela AR: PediatricCerebrovascular Disorders. New York, Futura Publishing Company, 1995,pp239-56.2. DeVeber G, Chan A, Monagle P, Marzinotttov , Amstrong D, Massicotte P,Leaker M, Andrew M, et al. Anticoagulation therapy in pediatric patients withsinovenous thrombosis; a cohort study. Arch Neurol. 1998; 55: 1533-37.3. Horowitz M, Purdy P, Unwin H, Carstens G 3rd, Greenlee R, Hise J, et al.Treatment of dural sinus thrombosis using selective catheterization and uroki-nase. Ann Neurol 1995; 38: 58-67.4. Wasay M, Bakshi R, Kojan S, Bobustuc G, Dubey N, Unwin HD. A non-ran-domized comparison of Local urokinase thrombolysis versus heparin antico-agulation in treatment of sagittal sinus thrombosis. Stroke 2001:32:2310-17.5. Kims Y, Suh JH. Direct endovascular thrombolytic therapy for dural sinusthrombosis; Infusion of altepase. AJNR 1997; 18: 639-45.6. Frey JL, Muro GJ, McDougall CG, Dean BL, Jahnke HK. Cerebral venousthrombosis; combined intrathrombus rtPa and intravenous heparin. Stroke1999; 30: 489-94.7. Barron TF, Gusnard DA, Zimmerman RA, Clancy RR. Cerebral venousthrombosis in neonates and children. Pediatr Neurol 1992; 8: 112-6.8. Griesmer DA, Theodorou AA, Berg RA, Spera TD. Local fibrinolysis in cere-bral venous thrombosis. Pediatr Neurol 1994; 10: 78-80.9. Wong VK, Lemesurier J, Franceschini R, Heikali M, Hanson R. Cerebralvenous thrombosis as a cause of neonatal seizure. Pediatr Neurol 1987; 3:235-7.10. Gebara BM, Goetting MG, Wang AM. Dural sinus thrombosis complicatingsubclavian vein catheterization; treatment with local thrombolysis. Pediatrics1995; 95: 138-40.556 J Pak Med Assoc

Local thrombolytic treatment of cerebral venous thrombosis in three paediatric patients

https://ecommons.aku.edu/cgi/viewcontent.cgi?article=1159&amp;context=pakistan_fhs_mc_med_neurol

Local thrombolytic treatment of cerebral venous thrombosis in three paediatric patients

Abstract

Similar works

Full text

Available Versions

eCommons@AKU