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|Year : 2014 | Volume
| Issue : 5 | Page : 521-524
Role of local thrombolysis in cerebral hemorrhagic venous infarct
Shaileshkumar S Garge, Virti D Shah, Nirmal Surya, Satish S Khadilkar, Pranav D Modi, Sharad B Ghatge
Department of Neurointervention Radiology and Neurology, Bombay Hospital and Medical Research Centre, Mumbai, Maharashtra, India
|Date of Submission||09-May-2014|
|Date of Decision||24-Aug-2014|
|Date of Acceptance||25-Sep-2014|
|Date of Web Publication||12-Nov-2014|
Shaileshkumar S Garge
Room No. 1502, MRC, 15th Floor, Doctors Quarters, Bombay Hospital, Marine Lines, Mumbai - 400 020, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Chemical thrombolysis in cerebral venous thrombosis (CVT) is one of the treatment options and the data is limited. Settings and Design: Prospective observational nonrandomized study. Subjects and Methods: This is a prospective study of 10 patients (six females and four males) admitted between May 2007 and June 2013. Grading system proposed by Department of Interventional Neuroradiology (INR), King Edward Memorial Hospital (KEM), Mumbai was used to grade the clinical status at admission. There were six patients with clinical Grade 3, two with Grade 4, and two with Grade 5. Patients with either Grade less than 3 or more than Grade 5 were excluded. Those patients, who were diagnosed with Cerebral venoussinous thrombosis (CSVT) but without hemorrhagic venous infarct and treated according to INR KEM criteria, were excluded from the study. Average duration of thrombolysis was 13 hours (range 10-18 hours). Average dose of urokinase was 12.2 lakh units (range 9.2-16.8 lakh units). Results: Six patients presented with clinical Grade 3 had modified Rankin Scale (mRS) sore of 1 at 30-day follow-up. Of the two patients with Grade 4, one had mRS 1 and the other had mRS 2 at 30-day follow-up. Of the two patients with Grade 5, one had mRS 2 at 30-day follow-up and the other did not respond to local thrombolysis and succumb to intracranial hemorrhagic infarct within 48 hours. Conclusion: This small prospective single-center study showed local dural venous thrombolysis significantly improves clinical and radiological outcome in patients with CVT. A randomized control trial with large sample size is needed to substantiate our findings.
Keywords: Cerebral venous thrombosis, hemorrhagic venous infarct, urokinase thrombolysis
|How to cite this article:|
Garge SS, Shah VD, Surya N, Khadilkar SS, Modi PD, Ghatge SB. Role of local thrombolysis in cerebral hemorrhagic venous infarct. Neurol India 2014;62:521-4
| ╗ Introduction|| |
Cerebral venous thrombosis (CVT) results in backpressure effect causing hemorrhagic venous infarcts and associated neurological deficits. Failure of CSF absorption due to high venous pressure leads to a further increase in intracranial pressure.  CVT is common in the Indian subcontinent and accounts for 10-20% of all young strokes in India.  The outcome of CVT is unpredictable and the mortality in most recent series varied between 10 and 20% and in patients with encephalopathy or impending encephalopathy the mortality is up to 53%. ,, Recanalization of thrombosed sinuses by chemical thrombolysis has been attempted with variable results. ,,, This report presents a small series of patients with CVT with cerebral hemorrhagic venous infarcts treated with local thrombolysis.
| ╗ Subjects and Methods|| |
This study presents the data of 10 (six females and four males) patients treated in the Department of Interventional Neuroradiology (INR) and Medical Neurological Intensive Care Unit (ICU) between May 2007 and June 2013. All patients had proven CVT with cerebral hemorrhagic venous infarcts. The grading of CVT was done using the criteria proposed by INR, King Edward Memorial Hospital (KEM), Mumbai, India:  Six patients with clinical Grade 3, two with Grade 4, and two with Grade 5 [Table 1].
|Table 1: INR KEM criteria for local thrombolysis for cerebral venous sinus thrombosis|
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The inclusion criteria for thrombolysis included: (i) Patients in severe grade (Grade 4 and 5) on admission with evidence of cerebral venous hemorrhagic infarct and restrictive venous outflow on cerebral angiogram and (ii) patients in clinical Grade 3 not responding to systemic heparin therapy, restriction to venous outflow on cerebral angiogram or patients in clinical grade less than 3 on presentation, but worsening on systemic heparin therapy. The exclusion criteria included: (i) patients who presented with either grades less than Grade 3 and responding to systemic heparin therapy or more than Grade 5; (2) patients who were diagnosed to have CVT, but without hemorrhagic venous infarct and treated according to INR KEM criteria, but were excluded from this study; and (iii) patients with major surgery or head injury (<6 weeks), gastrointestinal or genitourinary tract bleeding (<2 weeks), intracranial arteriovenous malformations, aneurysms or neoplasms, bleeding diathesis, international normalized ratio >1.7 or elevated activated partial thromboplastin time (aPTT), or platelet count less than 100,000.
All patients had detailed clinical history, neurological examination, and computed tomography (CT) or magnetic resonance imaging (MRI) scan with or without venography. On clinical and imaging (CT and MRI) findings, diagnosis of cerebral hemorrhagic venous infarct was suspected [Figure 1]. Routine hematological, biochemical, and bleeding profiles were done for all patients. All the patients had cerebral angiography for confirmation of diagnosis and patients fulfilling the inclusion criteria were selected for local thrombolysis using urokinase. All patients were shifted to the Medical Neurological ICU and close neurological monitoring was done. In case any patient deteriorated, an urgent CT brain scan was done to rule out progression of disease or fresh hemorrhage.
|Figure 1: CT brain plain showing hemorrhagic venous infarct in left occipital and venous infarct in the right occipital lobe. CT = Computed tomography|
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All procedures were digital subtraction angiogram (DSA) performed on Axiom Artis Zee, Siemens, Germany. A cerebral angiogram with late venous phase was done in all patients [Figure 2]a and [Figure 3]b. Patients fulfilling the inclusion criteria were taken for thrombolysis. A femoral venous access was secured with 6F sheath and femoral arterial access was secured with 5F sheath. A guiding catheter (Envoy 6F, Cordis) was placed in the jugular bulb. Mechanical clot maceration was done with the glidewire (Terumo 38) [Figure 2]b following which a microcatheter (Excelsior, Prowler, etc.) was navigated and placed in the thrombosed segment of sinus which was confirmed on a selective venogram [Figure 3]a.
|Figure 2: (a) ICA angiogram venous phase showing hanging veins appearance of the cortical veins and thrombosis of SSS, straight, and lateral sinuses. (b) Mechanical clot maceration with glidewire. ICA = Internal carotid artery, SSS = superior sagittal sinus|
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|Figure 3: (a) Microcatheter in dural sinus showing stasis of contrast. (b) Post thrombolysis complete resolution of cortical and venous sinus thrombosis|
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Urokinase infusion was started at the rate of 100,000 units/hour which was tapered down to 60,000 units/hour. Periodic check venograms were done [Figure 3]a. First check angiogram was done at 8-10 hours. Subsequent angiograms were performed at an interval of 6 hours. The infusion was continued until brisk flow in the sinuses achieved or significant clinical improvement with partial recanalization or a major complication occurred. After thrombolysis, patients were subjected to systemic heparinization till the resolution of hematoma and then shifted to oral anticoagulation for 6 months. Post-thrombolysis MR venography (MRV) showed persistent recanalization of cerebral venous sinuses [Figure 4]. After 6 months, anticoagulation was stopped and patients had undergone complete thrombophilia profile workup to decide whether patient needs long-term anticoagulation or not. Those patients who required emergency surgical decompression due to hemorrhagic venous infarct had undergone decompressive craniectomy without opening the dura or without clot evacuation. If there was no clinical improvement, these patients then underwent local thrombolysis after 48 hours (as in our series, patient no. 8).
|Figure 4: MRV showing complete resolution of the cortical and venous sinus thrombosis. MRV = Magnetic resonance venography|
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| ╗ Results|| |
The mean age of the patients was 41.4 years (range 26-60 years). All the patients presented with headache, vomiting, and altered sensorium. Six patients had associated seizures. Duration of symptoms varied from 8 to 48 hours. The clinical grade at admission was Grade 3 in six, Grade 4 in two, and Grade 5 in two patients. All 10 patients had restrictive venous outflow on DSA. Thrombosis of superior sagittal sinus (SSS) with one-sided transverse sigmoid sinus thrombosis was seen in four patients, three had thrombosis of transverse sigmoid sinus, two had thrombosis of SSS and bilateral transverse and sigmoid sinuses, and one had thrombosis of SSS alone. No patient had deep venous or straight sinus thrombosis.
All 10 patients fulfilled the inclusion criteria and were taken up for thrombolysis and there was no technical failure. The mean duration of thrombolysis was 13 hours (range 10-18 hours). Average dose of urokinase was 12.2 lakh units (range 9.2-16.8 lakh units).
Nine patients had rapid clinical improvement in symptoms of headache, vomiting, diplopia, and had seizure remission. One patient succumbed to large hematoma, raised intracranial pressure, and associated complications. Nine patients were asymptomatic from headache and vomiting by 24 hours. Focal neurological deficits did not show any change during the infusion period and showed gradual recovery over a period of 30 days. Maximum improvement was seen in the first 24 hours of infusion.
Six patients presented with clinical Grade 3 had modified Rankin Scale (mRS) score of 1 at 30-day follow-up. Two patients had mRS 4 at presentation, one had mRS 1, and one had mRS 2 at 30 days follow-up. Of the two patients with mRS 5 at presentation, one had mRS 2 at 30 days follow-up and the other had succumbed within 48 hours.
| ╗ Discussion|| |
Thrombosis of the cerebral dural sinuses and cerebral veins is a distinct cerebrovascular disease that, unlike arterial stroke, most often affects young adults and children. The estimated annual incidence is three to four cases per 1 million population and up to seven cases per 1 million among children. About 75% of the adult patients are women.  The mechanisms of neurological symptoms in CVT include: (1) Development of intracranial hypertension as the result of occlusion of the major venous sinuses and (2) localized edema of the brain, venous infarction, and petechial hemorrhages.  The causes of CVT are protean and in 30% of cases no underlying cause can be identified. 
The mainstay of management of thrombosis of the dural sinus and cerebral veins (CVT) is systemic heparinization. Along with heparinization, treatment of the underlying condition and prevention or treatment of complications is required. The systemic heparinization prevents thrombus propagation and increases the chances of recanalization. Anticoagulation is safe and can be used in patients with acute CVT who have intracranial hemorrhagic lesions.  Endovascular thrombolysis (with or without mechanical thrombus disruption) is a treatment to be used in experienced centers for severe cases or patients who fail to improve to anticoagulation. Multiple small series show good results with local thrombolytic therapy, but no randomized trials have been done.  Horowitz and colleagues treated 13 patients with extensive thrombosis of several sinuses via transfemoral route; 12 patients showed good results with sinus patency and good recovery.  Local thrombolytic therapy was done first by Scott et al. in 1988 via a frontal burr hole in patients with hemorrhagic infarct who had complete recovery.  Subsequently, several case reports and small case series have been reported highlighting the usefulness of intrasinus thrombolysis in CVT. In our study, local urokinase was relatively well tolerated by all the patients. Among our patients, one patient died and was related to the disease and not to thrombolytic therapy. 
Intravenous thrombolysis is associated with variable outcomes, as the concentration of the thrombolytic agent delivered at the site of occlusion is low. Thrombolysis is accelerated through direct intrasinus infusion of the thrombolytic agent.  The incidence of hemorrhage, though low, occurs with locally catheter-administered thrombolytic agents.  In our study, successful recanalization was documented in nine of the 10 patients. One patient who presented with Grade 5 and partial recanalization on check angiogram following thrombolytic therapy succumbed to raise intracranial pressure and secondary to large hemorrhagic venous infarct. Our small series showed that in situ thrombolysis can be advocated as first line therapy based on clinical and angiography criteria in severe clinical grade or patients with mild clinical grade deteriorating on systemic heparin therapy. Hemorrhagic venous infarct is not a contraindication for thrombolysis.  In our study, according to our inclusion criteria, rapid and sustained recovery was observed with local thrombolysis. Rapid resolution of neurologic dysfunction, particularly in patients unresponsive to intravenous anticoagulation with heparin, indicates the importance of infusing an adequate concentration of fibrinolytic agent at the site of thrombosis. Early therapeutic intervention may lead to successful clot lysis.
This study highlights the benefits of local thrombolysis in patients of cerebral hemorrhagic venous infarcts where systemic heparinization would have been a concern. This small case series has also demonstrated safety of direct thrombolytic infusions. The major limitation of our study is that it is an observational study and there is no control arm for comparison.
| ╗ Acknowledgement|| |
We sincerely thank to Dr. Inder Talwar and Dr. Sunila Jaggi for contributing imaging findings in this study And Dr K. E. Turel for Neurosurgery in these patients.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
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