CASE REPORTS Demonstration of Significant Resolution of Cerebral Sino-Venous Thrombosis Associated with Intravenous Recombinant Tissue Plasminogen Activator Vivek Misra, MD, Debra G. Elliott, MD, Eduardo Gonzalez-Toledo, MD, PhD, Roger E. Kelley, MD From the Departments of Neurology (VM, DGE, REK) and Neuroradiology (EG-T), Louisiana State University Health Sciences Center, Shreveport, LA. ABSTRACT BACKGROUND Cerebral sino-venous thrombosis (CVT) is commonly treated with anticoagulant therapy. There are reports of response to endovascular thrombolysis with or without mechanical aspiration in patients with clinical deterioration. CASE We present a 29-year-old man with acute onset of severe headache, found to have extensive CVT by magnetic resonance venography (MRV). His atypical presentation led to cerebral angiography that was complicated by global aphasia and right hemiparesis from left middle cerebral artery distribution ischemia. He received intravenous rt-PA (recombinant tissue plasminogen activator) within an hour of the procedure followed, 24 hours later, by intravenous heparin infusion with significant clinical improvement. The headache severity and CVT, on follow-up MRV, resolved significantly within 2 days. CONCLUSIONS We demonstrate clinical and neuroimaging response to systemic rt-PA in CVT. Thrombolysis may have a role in CVT management with an extended therapeutic window. Cerebral venous thrombosis (CVT) has a good outcome in up to 80% patients with anticoagulation.1 Patients with clinical deterioration, despite anticoagulation, may receive endovascular local thrombolysis with or without mechanical aspiration.2 In animal models, rt-PA is most effective in achieving recanalization.3 However, clinical response in patients, in terms of risks versus benefits, is not well established.4 Case Report A 29-year-old right-handed male presented with sudden onset of severe headache with initial computed tomography (CT) brain reported to be negative. The magnetic resonance imaging (MRI) brain (Fig 1A and B) and magnetic resonance venogram (MRV) (Fig 2A) performed on Day 1 of presentation showed extensive CVT. Due to the acute presentation and no significant change in serial red cell counts in cerebrospinal fluid (CSF), the treating service had suspicion of sub-arachnoid hemorrhage. He was not anticoagulated and underwent cerebral angiography, which demonstrated CVT with no vascular anomaly. Immediately after angiography, he developed global aphasia and dense right hemiparesis. The Neurology Service was then consulted and, after CT brain excluded hemorrhage, a clinical diagnosis of angiography-related left middle cerebral artery (MCA) distribution ischemia was made, and he received 348 ◦ Keywords: Sino-venous thrombosis, stroke, tissue plasminogen activator, vascular neuroimaging Acceptance: Received August 30, 2006, and in revised form August 30, 2006. Accepted for publication September 1, 2006. Correspondence: Address correspondence to Roger E. Kelley, MD, Department of Neurology, LSU Health Sciences Center-Shreveport, 1501 Kings Highway, Shreveport, LA 71103. E-mail: rkelly@lsuhsc.edu. J Neuroimaging 2007;17:348-349. DOI: 10.1111/j.1552-6569.2006.00074.x 0.9 mg/kg intravenous rt-PA within 30 min of symptom onset. Twenty-four hours later, after follow-up CT brain excluded hemorrhagic transformation of infarct, he received a loading dose of intravenous heparin 80 units/kg followed by infusion to maintain the partial thromboplastin time between 46 and 70 sec. His speech and strength improved significantly within 24 hours after thrombolysis. Follow-up neuroimaging 2 days after thrombolysis, and within 24 hours of heparinization, showed significant sinus recanalization. The headache severity improved dramatically. He had mild word finding difficulty and right pronator drift 7 days after presentation. He was found to have low protein S function level of 53% (normal 60-185%). Discussion Early death in CVT results from transtentorial herniation due to mass effect, diffuse edema, and multiple lesions. Fatal outcome was more likely in patients with admission GCS (Glasgow Coma Scale) score <9, seizure, altered mental status, right-sided hemorrhage, deep cerebral venous involvement and posterior fossa lesions.5 Over 90% of patients have gradually progressive headache but some have acute presentation resembling aneurysmal subarachnoid hemorrhage.6 The development of left MCA ischemia in this patient, following cerebral arteriography, led to consideration of Copyright C 2007 by the American Society of Neuroimaging Fig 1. MRI Brain - Axial FLAIR (A) and DWI (B) showing superior sagittal sinus thrombosis not associated with infarction, compared to post-thrombolytic study (D and E) showing partial recanalization of superior sagittal sinus with an acute left middle cerebral artery infarct (4). Coronal T1-weighted MRI with contrast (C) demonstrating thrombosis of superior sagittal sinus (1), torcula (2) and transverse sinuses (3) which is significantly improved following thrombolysis (F). (Fig 2) is unlikely due to heparin, as this therapy requires significantly longer time (many days) to achieve recanalization.3,7 The clear response to thrombolysis on neuroimaging and headache severity within 2 days of presentation without ill effects suggests that rt-PA may be useful in subacute management of CVT. References 1. 2. 3. Fig 2. Magnetic resonance venogram (MRV) before (A) and 2 days after thrombolysis (B) showing significant recanalization of superior sagittal sinus (1), straight sinus (2), torculum (3) and both transverse (4) and sigmoid sinuses (5) following thrombolysis. 4. intravenous rt-PA due to symptom onset within the 3-hour time window and this was associated with improvement in right hemiparesis. The presence of a nonhemorrhagic infarct corresponding to the left MCA territory on MRI fluid attenuated inversion recovery sequences (FLAIR) and diffusion weighted imaging (DWI) after thrombolysis, and its absence on corresponding sequences immediately prior to angiography (Fig 1) clearly indicates that it is an arterial infarct. The dramatic improvement in headache severity and CVT seen by MRV within 2 days of thrombolysis and within few hours of heparin infusion 5. 6. 7. Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med 2005;352:1791-1798. Canhao P, Falcao F, Ferro JM. Thrombolytics for cerebral sinus thrombosis: a systematic review. Cerebrovasc Dis 2003;15:159166. Rottger C, Madlener K, Heil M, Gerriets T, Walberer M, Wessels T, Bachmann G, Kaps M, Stolz E. Is heparin treatment the optimal management for cerebral venous thrombosis? 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